European Guidelines for Quality Assurance in Mammography Screening

EUROPEAN COMMISSION

PUBLIC HEALTH

EUROPEAN GUIDELINES FOR QUALITY ASSURANCE

IN MAMMOGRAPHY SCREENING

2nd edition

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EUROPE AGAINST CANCER

JUNE 1996

EUROPEAN COMMISSION • Europe Against Cancer Programme · Radiation Protection Actions ·

A great deal of additional Information on the European Union is available on the Internet. It can be accessed through the Europa server (http://europa.eu.int)

Cataloguing data can be found at the end of this publication

Luxembourg: Office for Official Publications of the European Communities, 1996

ISBN 92-827-7454-6

© ECSC-EC-EAEC, Brussels · Luxembourg, 1996

© Cover: Pablo Picasso, Les Demoiselles d'Avignon, Paris (June-July 1907) Oil on canvas, 8' χ 7'8" (243.9 χ 233.7 cm) The Museum of Modern Art, New York. Acquired through the Lillie P. Bliss bequest. Photograph © 1996, The Museum of Modern Art, New York

Reproduction is authorized, except for commercial purposes, provided the source is acknowledged

Printed in Belgium

List of contents

I - 1 EUROPEAN GUIDELINES FOR QUALITY ASSURANCE IN MAMMOGRAPHY SCREENING 1. Introduction 2. European network of reference centres (EUREF) 3. Key organisational aspects

Conditions for breast cancer screening Objectives

4. QA programme Identification of the target population Data-administrative System Screening age groups and intervals: The Screening Examination: Professional communication: Radiation Protection Considerations: Cost-effectiveness calculations: Training: Performance Indicators:

5. Quality Maintenance 6. Assessment Process

I - 2. THE IMPORTANCE OF THE RADIOGRAPHER IN MAMMOGRAPHY SCREENING Compression Positioning Personal communication Quality Assurance procedures Teamwork Training

I - 3 THE ROLE OF THE RADIOLOGIST IN THE SCREENING PROGRAMME Introduction Quality issues Performance Assessment Teamwork Interval cancers

-1 - 2 - 2 - 2 - 2 - 3 - 3 - 4 - 4 - 4 - 4 - 4 - 5 - 5 - 5 - 6 - 7

-8 -8 -8 -9 -9 -9 -9

-10 -10 -10 -10 -10 -11 -11

I - 4 BIBLIOGRAPHY 1-12

GUIDELINES AND PROTOCOLS

II- A QUALITY ASSURANCE IN THE EPIDEMIOLOGY OF BREAST CANCER SCREENING Introduction II - A -1 Block I - Local conditions governing the screening process II - A - 3 Block II - Invitation scheme II - A - 7 Block III - Screening process and further assessment II - A -12 Block IV - Evaluation / outcomes of screening It - A -19 Block V - Disease stage of screen-detected cancers II - A - 27 Block VI - Treatment of screen-detected cancers II - A - 32 Block VII - Follow up and ascertainment of interval cancers II - A - 37 Block VIM - Impact on breast cancer mortality II - A - 40 Acknowledgements II - A - 41 Glossary of terms II - A - 42

I I -Β CYTOPATHOLOGY GUIDELINES Introduction II - Β -1 Registering basic information I I - B - 2 Reporting categories II - Β - 3 Quality assurance II - Β - 5

Il - C QUALITY ASSURANCE GUIDELINES FOR PATHOLOGY IN MAMMOGRAPHY SCREENING

INTRODUCTION

MACROSCOPIC EXAMINATION OF BIOPSY AND RESECTION SPECIMENS Biopsy Specimens Mastectomy Specimens Axillary Dissection Specimens

USING THE HISTOPATHOLOGY REPORTING FORM Introduction Recording Basic Information Recording Benign Lesions Classifying Epithelial Proliferation

I I - C - 1

- C - 1 - C - 1 - C - 3 - C - 4

- C - 6 - C - 6 - C - 6 - C - 7 C - 1 2

C - 1 5 C - 1 5 C - 1 5

CLASSIFYING MALIGNANT NON-INVASIVE LESIONS II High Nuclear Grade DCIS II Low Nuclear Grade DCIS II Intermediate Nuclear Grade DCIS II - C -16 Mixed Types II - C -16 Other histological types II - C -16 Paget's disease II - C -17 Diagnosing Microinvasion II - C -17 Classifying Invasive Carcinoma II - C -18 Invasive cribriform carcinoma II - C -18

RECORDING PROGNOSTIC DATA

REFERENCES

- C - 1 9

- C - 2 4

INDEX FOR SCREENING OFFICE PATHOLOGY SYSTEM

MEMBERSHIP OF WORKING GROUP

I I - C - 2 6

II - C - 31

Il - D- THE EUROPEAN PROTOCOL FOR THE QUALITY CONTROL OF THE PHYSICAL AND TECHNICAL ASPECTS OF MAMMOGRAPHY SCREENING

Executive summary

1. Introduction to the measurements

2. Description of the measurements 2.1 X-ray generation and control

2.1.1 X-ray source Focal spot size Focal spot size: star pattern method Focal spot size, slit camera method Focal spot size, pinhole method Source-to-image distance Alignment of X-ray field/image receptor Radiation leakage Tube output

2.1.2 Tube voltage Reproducibility and accuracy Half Value Layer

2.1.3 AEC-system Optical density control setting: central value and difference per step

- D - 1

- D - 3

-D -D -D -D -D -D -D -D -D - D - 7 - D - 7 - D - 8 - D - 8 - D - 8 - D - 9 - D - 9

Guard timer II I-Short term reproducibility

Long term reproducibility Object thickness compensation Tube voltage compensation

2.1.4 Compression Compression force Compression plate alignment

2.2 Bucky and image receptor 2.2.1 Anti scatter grid

Grid system factor Grid imaging

2.2.2 Screen-film Inter cassette sensitivity and attenuation variation Screen-film contact

2.3 Film processing 2.3.1 Base line performance processor

Temperature Processing time

2.3.2 Film and processor Sensitometry Daily performance Artifacts

2.3.3 Darkroom Light leakage Safelights Film hopper Cassettes

2.4 Viewing conditions 2.4.1 Viewing box

Luminance Homogeneity

2.4.2 Ambient light Level

2.5 System properties 2.5.1 Dosimetry

Entrance surface air kerma 2.5.2 Image Quality

Spatial resolution Image contrast Threshold contrast visibility Exposure time

3. Daily and weekly QC tests.

4. Definition of terms

5. Tables

6. Bibliography

Appendix 1: Calculation of film-parameters

Appendix 2: A method to correct for the film curve

Appendix 3: Typical values for other spectra and densities

Appendix 4: Sample Data Sheets

I-

D-9 D-10 D-10 D-10 D-10 D-10 D- 11 D - 11 D-12 D-12 D-12 D-12 D-12 D-12 D-12 D-14 D-14 D-14 D-14 D-14 D-14 D-15 D-15 D-15 D-15 D-16 D-16 D-16 D-17 D-17 D-17 D-17 D-18 D-18 D-19 D-19 D-19 D-19 D-19 D-20 D-20 D-20

l - D - 2 1

I - D - 22

I - D - 26

I - D - 29

I - D - 33

I - D - 34

I - D - 35

I - D - 37

ANNEXES

ANNEX 1: RECOMMENDATIONS OF THE COMMITTEE OF CANCER EXPERTS ON BREAST CANCER SCREENING Ill -1

ANNEX 2: EUREF PROTOCOL Ill - 3 ANNEX 3: POPULATION SCREENING ACT ( The Netherlands) Ill - 5

ANNEX 4: COUNCIL OF EUROPE , COMMITTEE OF MINISTERS, RECOMMENDATION No. R (94)11 ON SCREENING AS A TOOL OF PREVENTIVE MEDICINE . . . . 111-11

ANNEX 5: EUROPEAN PROTOCOL ON DOSIMETRY IN MAMMOGRAPHY (EXECUTIVE SUMMARY OF EUR 16263) 111-17

ANNEX 6: EUROPEAN CONSENSUS ON THE ROLE OF GENERAL PRACTITIONERS IN WOMEN'S CANCER SCREENING Ill - 22

Definition of Terms:

Quality Assurance as defined by the WHO (1982): "All those planned and systematic actions necessary to provide adequate confidence that a structure, system or component will perform satisfactorily in service (ISO 6215-1980). Satisfactory performance in service implies the optimum quality of the entire diagnostic process-i.e., the consistent production of adequate diagnostic information with minimum exposure of both patients and personnel."

Quality Control as defined by the WHO(1982): "The set of operations (programming, coordinating, carrying out) intended to maintain orto improve [. . . ] (ISO 3534-1977). As applied to a diagnostic procedure, it covers monitoring, evaluation, and maintenance at optimum levels of all characteristics of performance that can be defined, measured, and controlled."

European Guidelines for QUALITY ASSURANCE in Mammography Screening 2nd edition (JUNE 1996)

I - 1 EUROPEAN GUIDELINES FOR QUALITY ASSURANCE IN M A M M O G R A P H Y SCREENING

1. Introduction

Revision of the Guidelines for Mammography Screening has become necessary in the light of experience gained from the operation of screening programmes in Europe since the publication of the first edition. For this second edition we have included full guidelines for epidemiology and pathology. Population screening for breast cancer is a major public health intervention and experience shows that suitable performance parameters can only be achieved through strict adherence to Quality Assurance (QA) guidelines. Since screening is targeted essentially at asymptomatic women, the narrow balance between benefits and undesirable effects is completely dependent on programme quality. Achievement of the objective, mortality reduction, is inevitably long term. There are, however, important early performance indicators which can predict outcome and which therefore must be accurately documented. High quality data are essential.

This document outlines the requirements of a QA programme for a number of aspects of a screening system, but does not yet attempt to define guidelines for treatment. It does, however, give more detailed guidance for the medical diagnostic and technical aspects of the screening process itself.

The effectiveness of any screening programme is directly related to the quality of the individual parts ofthat programme. For high quality mammography screening, the following aspects are of prime importance:

• Epidemiology: Epidemiological support underpins the entire process of a screening programme, from the organisational and administrative aspects, through implementation to evaluation and assessment of impact.

• Physico-Technical: The quality of the imaging process is linked to both the image quality and the dose absorbed by breast tissue. Compliance with the criteria on image quality and breast dose, defined for radiographic examinations of the breast (CEC EUR 16260, European Guidelines on Quality Criteria for Diagnostic Radiographic Images, September 1995) is essential. Performance has to be monitored by regular measurements of appropriate physical and technical parameters in order to verify that a satisfactory and consistent technique is being employed. The results of this Quality Control (QC) of the technical aspects can then be assessed by an independent service. This enables the comparability of the performance of each centre and ensures that at least the basic level of performance required by a QA Programme is being achieved.

• Radiography: The radiographer is in most cases the only member of the professional team who has physical contact with every woman attending for screening. Adequate technique requires proper training followed by strict and continual adherence to performance guidelines.

• Radiology: Radiologist screening performance will be maximised by appropriate training, adequate on-going experience and sufficient volume of work with evaluation and appraisal of activities.

ι - 1


• Pathology: The success of a breast screening programme depends heavily on the quality of the cytology and pathology services. The accurate and standardized categorization of screen detected abnormalities requires specialized skills and training.

• Treatment: Because of the enormous variation in treatment practices throughout Europe, it is not considered practical at this stage to lay down detailed guidelines on a QA system for treatment. In any given country or district the method and outcome of treatment requires to be closely audited.

No screening programme should be undertaken without clearly established goals, dedicated staff training and proper QA. Training programmes should be established by centres of expertise. The certification of knowledge acquired during training is recommended.

2. European network of reference centres (EUREF)

EUREF is the European network of reference centres for breast cancer screening established by the "Europe against Cancer" programme. Its office acts as a training co-ordinating and documentation centre. The "Europe against Cancer" programme is committed to ensuring that the pilot breast screening projects funded by it, achieve sufficient quality and expertise to function as Quality Assurance Reference Centres in their own country. To this end, EUREF is charged with the responsibility of responding to and coordinating a Quality Assurance training requirement in a given programme. The nature of this response would be to facilitate contacts and training activities between the pilot study concerned and the source of expertise seen as most suitable by the "Europe against Cancer" programme. EUREF should further monitor the progress of the programme in question to the point where a satisfactory outcome has been achieved. EUREF is also prepared to offer advice on sources of training and coordination to other breast screening programmes upon request. The full protocol is listed in annex III D

3. Key organisational aspects

Conditions for breast cancer screening

Screening for breast cancer by means of mammography has been shown to be effective in reducing breast cancer mortality in several studies. High compliance is crucial in maximising the effect on mortality reduction.

The process of cancer screening is one where asymptomatic women are invited to undergo a test procedure aimed at identifying malignant disease. In a screening situation it is of particular importance that both sensitivity and specificity are maintained at a high level. This can only be achieved when mammographie screening is carried out by well trained, experienced personnel, using high quality equipment purchased and maintained according to the European protocol for the Quality Control of the Technical Aspects of Mammography Screening. It is of major importance for the QA Programme to have a system which will detect cancers occurring in the screened population during the intervals between successive screenings. The identification of these interval cancers is necessary to assess performance. This aspect of the programme can only be fully evaluated with the existence of an accurate and up-to-date cancer register.

Objectives

It must be understood that although the aim of the screening programme is to reduce mortality from breast cancer, this effect cannot be measured until an interval of approximately a decade from the commencement of screening. Adequate and accurate information is required to measure effectiveness. It is important that clear operational objectives be employed, as listed below:

1 - 2


1. To identify and invite eligible1 women for mammography screening. 2. To maximise compliance in the eligible population. 3. To ensure that mammography of the highest possible standard is achieved and that the films are read

by personnel with proper training and proven skills in this area. 4. To maximise the acceptability of the service. 5. To provide prompt and effective further investigations and treatment where indicated. 6. To minimise the adverse effects of screening. 7. To optimize cancer detection. 8. To perform regular audit of the activities of the programme and to provide appropriate feedback. 9. To provide a cost-effective service. 10. To ensure that all staff undergo regular training and professional development.

4. QA programme

A QA Programme for mammography screening has to be considered under headings relating to all elements in the programme from the identification of the population to be screened to the evaluation and identification of screen-detected abnormalities. Ideally, a comprehensive QA Programme in breast cancer screening should also take into account an audit of treatment, but, in the wide context of Europe, with all the variations involved, this is not seen as practical in the present instance. The programme director has overall responsibility for implementing, evaluating and updating the QA Programme. There must also be a nominated individual who is accountable for the implementation of professional guidelines in each individual discipline. The radiologist has a co-operative role with radiographers and physicists for technical aspects of screening, he/she is wholly responsible for the reading and interpretative aspects. Multidisciplinary analysis of individual case management and overall programme outcomes must be undertaken with the relevant professional specialities.

A screening programme must be backed by comprehensive QA, covering not only tests to ensure optimum choice and performance of equipment and accessories, but also optimum performance of staff in all disciplines. Every mammography facility must have a QA Manual. This Document provides guidance towards the creation of such a QA Manual. However, the physico-technical protocols can be regarded as a framework. Any QA Manual must set out the essential features of all checks, tests and procedures in the QA Programme, together with indications of who takes action in the light of test results, and who ensures that this action is satisfactory. It must also be subject to almost continuous review as technology advances, and knowledge and experience are gained.

Identification of the target population

Ideally each population to be screened should be derived from a population register. In the absence of such a register, a listing of women in the target population will need to be compiled. For the screening programme to have maximum effect it is essential that the screening register is both complete and accurate. The types of error which occur in registers relate to wrong address, wrong name, wrong date of birth, mistakes in other personal data, spelling and typing mistakes and wrong reference numbers. The register must be regularly updated as in some urban populations the mobility may amount to 20% per annum. Without a defined population, it is impossible to calculate accurately the attendance rate. The higher the attendance rate achieved, the greater the potential benefit to the target population.

1 See epidemiology glossary for full definition

1-3


Data-administrative System

The data-administrative system provides a basis for programme analysis and facilitates regular assessment of results and for feedback of data to all involved in the screening programme.

The Call/Recall System should: • Issue all invitations to screening • Issue reminder letters to non-attenders. • Issue appointments for assessment of screen detected abnormalities.

Screening age groups and intervals:

The majority of scientific publications demonstrate a breast cancer mortality reduction from screening in the age group 50 - 69. Routine population screening below the age of 50 is not recommended.

The optimal screening interval is likely to be from 2 to 3 years.

The Screening Examination:

For each woman's initial screening examination, a two view technique should be employed, using a medio-lateral oblique combined with a cranio-caudal projection. This examination must be carried out by radiographers who are properly trained and have documented performance skills.

Professional communication:

The successful conduct of the screening programme is a multidisciplinary exercise and adequate results will not be achieved without regular formal case management reviews. This is best organized in the format of a multidisciplinary review meeting.

Radiation Protection Considerations:

All practices which involve radiological examinations of asymptomatic individuals shall be consistent with the general principles of radiation protection:

• all exposures shall be medically and epidemiologically justified by the benefits they produce in relation to potential hazards;

• all exposures shall be kept as low as reasonably achievable;

• appropriate dose constraints shall be applied;

• any alternative techniques likely to prove at least as effective from the diagnostic point of view and presenting less potential hazards should be used.

All medical and paramedical staff involved in radiological examinations of asymptomatic individuals should have received adequate training relevant to the techniques used. Such staff also should have acquired competence in radiation protection according to article 2 of the Council Directive of 3 September 1984 laying down basic measures for the radiation protection of persons undergoing medical examination or treatment (57).

1-4


Cost-effectiveness calculations:

Prior to inception the programme should undergo cost benefit analysis to demonstrate probable achievement of its targets. Cost effectiveness is an important part of QA and a calculation model (MISCAN) developed by the Erasmus University in Rotterdam (The Netherlands) has been tested in several screening programmes throughout Europe.

Training:

It is fundamental to the success of screening that all staff involved in the programme must have attended a course of instruction at an approved training centre. Professional staff may also require a period of secondment to the centre (not necessarily the same training centre).

Performance Indicators:

1 The Application of the Results of the Screening Programme to the Q.A. Programme The results of a screening programme provide statistics which form the basis of the most accurate performance indicators for radiologists. A number of parameters therefore require to be checked regularly and the information system must be capable of providing the appropriate data. The first and most immediately available figure is the Recall Rate. Earlier recommendations were that less than 10% of screened women should be recalled for assessment. Recent experience suggests that 5% or below is a more realistic target and one which certainly should be aimed for.

2 Crude Cancer Detection Rate It has been stated that in a previously unscreened population in Northern and Western Europe, a screening programme should detect not less than 5 invasive cancers per 1000 women screened. The detection rate at initial screening depends on the incidence of breast cancer which is relatively low in Southern and Eastern Europe compared to the North and West. Experience has already shown that a number of programmes detect a considerably higher rate than this, but to allow for the considerable variations which may occur in different populations, the figure of 3 times the numerical value of the local annual incidence rate should be adhered to in the prevalent round. In the incident rounds of screening at a two years interval, 1,5 times that value is acceptable.

3 Small Cancer Detection Rate The detection of small invasive cancers is regarded as important in terms of mortality reduction and as an indicator of image quality and radiologist performance. It is recommended that at least 25% of screen detected cancers should be of a size less than or equal to 10mm.

4 Interval Cancer Rate As a direct consequence of a long screening interval (2-3 years) it will be some considerable time before this rate becomes fully available, but it again forms a useful indication as to the efficiency of the screening programme.

5 Positive Predictive Value of Recommendation for Open Biopsy This value should be in order of at least 50% in the initial screen and increase in the following screening rounds (see epidemiology glossary).


Monitoring performance indicators is an organisational responsibility to be carried out by the project leader or relevant professional and administrative disciplines. In terms of the overall programme performance, the following items should be recorded:

1. Number of women invited. 2. Number of women screened. 3. Number of women recalled for technical reasons. 4. The time interval between invitation to screening and referral to assessment unit. 5. Type and number of additional tests performed. 6. Number of fine needle aspiration cytology or core biopsy examinations performed. 7. Number of preoperative localisations performed. 8. Number of women subjected to short term recall.

5. Quality Maintenance

1 Double Reading It is highly recommended, and in a decentralised system essential, that screening mammograms are read by two radiologists acting independently. Second reading should be performed by a radiologist trained and experienced in mammography screening. Decentralised second reading is not recommended. The administering radiologists should be able to extract data from screening records to monitor individual radiologist performance. These records, of course, must remain confidential within the profession.

2 Internal Review Each Screening/Assessment Centre should hold local meetings on a regular basis to review screening programme results and to review in detail films of: (a) Early cancers detected (b) Interval cancers (c) Early cancers missed by one or more film readers

3 Review Meetings On a wider basis, regular meetings should be held to review radiologist performance and to cover problems such as those outlined above under Local Meetings and other topics related to the radiological aspects of the QA Programme, e.g. performance of ultrasound or stereotactic fine needle aspiration cytology.

4 Structure and Monitoring of QA QA is best achieved by the help of some qualified national external authority. Visiting by staff to other screening units has been found of benefit in maintaining quality. It is also of benefit to occasionally receive visits by acknowledged expert staff from other major centres or a reference centre.

5 Technical Quality Control Each Screening unit must perform Technical Quality Control on their mammographie devices and equipment, in order to assure the appropriate image quality of the mammograms of each woman attending the screening service. Some of the daily or weekly quality control actions can be performed by the local staff. More elaborate measurements should be performed every six months by an independent authority.

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European Guidelines for QUALITY ASSURANCE in Mammography Screening 2nd

edition (JUNE 1996)

6. Assessment Process

The outcome of assessment of screen-detected abnormalities must be closely audited and the results

recorded. The objectives and measurements are given below:

OBJECTIVE MEASUREMENT

To minimise the number of women

referred unnecessarily for further tests.

Onward referral to assessment.

To minimise the number of false

negative results in screened women.

In the prevalent round the number of invasive

cancers presenting in screened women in the

subsequent 12 or 24 months.

3. To maximise the number of cancers

detected.


cancers detected in women invited and

screened. The numbers may vary according

to national incidence.

4. To maximise the number of small

cancers detected.


cancers s10 mm in diameter, pathological

measurement, detected in women invited and

screened.

To minimise the number of

unnecessary invasive procedures.

Benign to malignant biopsy ratio.

The target values are given in the Epidemiology guidelines and other relevant sections of this document.

AUTHORS:

M. Broeders (Nijmegen NL)

M. Codd (Dublin IRL)

A. Kirkpatrick (Edinburg UK)

Ν. Perry (London UK)

M. Thijssen (Nijmegen NL)

S. Törnberg (Stockholm S)

C. de Wolf (European Commission LUX)

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I - 2. THE IMPORTANCE OF THE RADIOGRAPHER IN M A M M O G R A P H Y SCREENING

This is a brief summary of the role of the radiographers in mammography screening. Full Q A guidelines are at present been drawn up.

Mammography as a screening test for breast cancer has to meet stringent quality requirements. These requirements can only be met when a comprehensive Quality Assurance (QA) programme is in place. The requirements for a complete QA programme must include the role of the radiographer in the screening system and/or QA requirements for radiographers. This chapter provides a brief outline of quality assurance for radiographers in mammography screening.

For the majority of women attending the programme, the radiographer is the only health professional they will encounter. The radiographer has the following tasks:

To perform an excellent quality mammogram from both the positioning and technical point of view. To have the social skills to support the woman during the examination and encourage her to attend regularly. To carry out quality assurance procedures.

Compression

Adequate compression is essential for a high quality mammogram. Compression reduces radiation dose to the woman. It contributes to improving the image quality, because it provides a uniform thickness of the breast and separates structures within the breast. Since compression reduces the thickness of the breast, scattered radiation diminishes, thus improving contrast. To compress the breast may cause brief discomfort, therefore the radiographer should explain the importance of the compression before starting the procedure. A footpedal operated compression plate is essential in order to allow the radiographer to use both hands for positioning the breast.

Positioning

Breast positioning is an art. When evaluating a mammogram, incorrect positioning is the most common problem. The skills required to perform optimal mammographie positioning are high. When the woman is able to cooperate and to relax, the radiographer find positioning easier to perform.

The standard views in a mammography screening programme are:

The cranio-caudal view

The medio-latero-oblique view

Common criteria for image quality assessment are:

Adequate compression Good technical quality Symmetrical images No movement unsharpness No skin folds Correct standardized labelling

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The most important criteria for an optimal cranio-caudal view are:

The breast is centrally positioned with the nipple in profile. One should visualize as much as possible of the breast tissue. The posterior breast tissue should be pulled forward. A small amount of pectoral muscle is sometimes seen, indicating that the breast has been positioned as far forward as possible on the film.

The most important criteria for the medio-latero-oblique view are:

The whole breast tissue is imaged. The pectoral muscle shadow is seen to nipple level. The nipple should be in profile. The ¡nframammary angle is clearly shown.

Personal communication

When a pleasant and informative atmosphere is created, the woman is more likely to relax. The radiographer should answer enquiries and explain the procedure in order to make the woman feel at ease. She should be friendly, caring and professional. She should treat the woman the way she would like to be treated herself.

Quality Assurance procedures

A technically optimal mammogram is dependent on a number of factors, such as equipment, screen-film combination, cassettes, processing conditions, darkroom, etc. Image quality standards must be established. To maintain the highest standard of image quality, a quality assurance programme has to be implemented. It is the radiographer's duty to carry out quality control procedures, such as performing a phantom image, a sensitometric stepwedge, etc.

Teamwork

The radiographer should participate in all multidisciplinary team meetings. Feedback is essential to maintain a high-standard or improve, in particular, regular communication with the radiologist is vital.

Training

Radiographers have a key role in obtaining and maintaining recognized targets for the success of a mammography screening programme. Training in the various aspects of her work is mandatory.

AUTHORS: H. Rijken (Nijmegen NL) J Caseldine (Sheffield UK)

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I - 3 THE ROLE OF THE RADIOLOGIST IN THE SCREENING P R O G R A M M E

Introduction

The radiologist is directly involved with the overall quality of service delivery, and in particular all aspects of interpretation and proper work up so that a woman may be regarded as optimally benefitting from a screening programme. A sufficient proportion of the radiologist's working time should be spent in breast imaging and following specialised training, adequate numbers of mammograms must be read in order to preserve skills and competence. If possible the radiologist should act as clinical director of the programme.

Quality issues

The radiologist must ensure that a satisfactory quality assurance system is in place with sufficient quality control mechanisms to provide adequate image quality. Recognition must be given to the importance of optical density of mammograms with regard to small cancer detection rates. Two view mammography is expected for the woman's first screening attendance, and previous mammograms should be available and displayed for comparison purposes when a woman has her subsequent (incident) round films read. It is the responsibility of the radiologist in charge of the screening programme to ensure that failsafe mechanisms are in place so that women with radiological abnormalities requiring further assessment are not denied suitable investigations on the basis of a normal clinical examination or failure to inform and communicate with the woman. He/she should ensure that staff in the screening unit are aware of the concepts of complying with minimum standards, constantly seeking to maintain and improve skills, and partaking in recognised external quality assessment(EQA) schemes.

Performance

Required standards (performance indicators) may be regarded as minimum and expected. Expected standards are scientific estimates of targets required to achieve a mortality reduction of 25% in the target age group. Minimum standards are set lower than this and should be regarded as a level that must be achieved by all screening units regardless of statistical variation. Failure to meet minimum standards should be followed by external investigation as to possible causes. Geographical variation in the incidence of breast cancer may warrant different target standards for different countries.

One of the key surrogate measures for a radiologist in estimating success of a screening programme in terms of mortality reduction is the ability to detect small cancers. Tumours of less than 15mms in diameter have been shown to represent a good prognosis and it is expected that at least 50% of screen detected invasive cancers will be of such a size. Tumours of less than 10mms in diameter should account for 25% of screen detected invasive cancers as this size reflects both film quality and radiological performance. It is accepted than lymph node status, tumour grade and tumour type are also important factors and the radiologist must ensure that full and adequate recording of such basic histological data is made in the screening programme. It is believed that removal of ductal carcinoma in-situ (DCIS), particularly of the high grade or risk type, contributes to long term reduction in mortality. Its detection is also an indicator of image quality, radiologist prediction and assessment adequacy. It is expected that DCIS should account for at least 15% of screen detected cancers within a programme.

Assessment

The recall of women from the screening programme for full assessment creates anxiety and it is the radiologist's responsibility to ensure that sensitivity and specificity are optimal so that women are not subjected to unnecessary anxiety. At assessment a full range of facilities including ultrasound, micro-focus magnification and image guided cytological analysis must be available. The radiologist leading the imaging assessment of a woman referred from the screening programme should also be involved in screen reading

I - 10


and in this way feed back of information is obtained. It is also the responsibility of the assessing radiologist to ensure that women are suitably assessed in terms of all necessary procedures being performed and that unnecessary intervention or creation of anxiety is avoided. Short term recall of women with screen detected abnormalities creates anxiety and should be avoided in all but exceptional circumstances. It is not regarded as good practice to subject a woman to short term recall following the screening process alone, without clinical and imaging assessment.

Teamwork

The radiologist should encourage the formation of a skilled multidisciplinary assessment team for women referred from the screening programme and ensure that regular multidisciplinary review meetings are held within the programme to provide feedback to involved professionals of a radiological, cytological and histological nature. Such activity will help minimise the number of benign biopsies performed, which should be less than the number of cancers detected in the programme.

Interval cancers

It is vital that mechanisms are in place to identify all breast cancers arising in the target screened population, and that the programme is informed of interval cancers in order to fully assess the quality of programme performance. In addition the radiologist must ensure that a suitable mechanism exists for the review and audit of such interval cancers. The radiologist should encourage all surgeons within the locality of a screening programme to perform mammography prior to treatment in all cases of symptomatic breast cancer.

AUTHORS: N. Perry (London UK) A. Kirkpatrick (Edinburgh UK)

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1-4 BIBLIOGRAPHY

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3. Baum M. Screening for breast cancer, time to think- and stop. Letter. Lancet 1995;346:436-437.

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Nos 1/3


II

Guidelines &

Protocols


II- A QUALITY ASSURANCE IN THE EPIDEMIOLOGY OF BREAST CANCER SCREENING

Authors:

Drs. M.J.M. BROEDERS Vakgroep med. informatiekunde, epidemiologie & statistiek Kapitterweg 54 6500 HB Nijmegen NEDERLAND

Dr. M. B. CODD Dept of Epidemiology, Mater Miseri Cordiae Hospital Eccles Street DUBLIN 7

IRELAND

Dr. N. ASCUNCE Gobierno de Navarra Programme Cancer de Mamma C/ Condo Uliveto 9 - 30 E-31002 PAMPLONA ESPAGNE

Dr. A. LINOS Inst, of Preventive Medicine Enviromental & Occ. Health 227, Kifissias Ave. Anavryta GR- 14561 KIFISSIA, ATHENS GREECE

Prof. A.L.M. VERBEEK Vakgroep med. informatiekunde, epidemiologie & statistiek Kapitterweg 54 6500 HB Nijmegen NEDERLAND


Table of contents

QUALITY ASSURANCE IN THE EPIDEMIOLOGY OF BREAST CANCER SCREENING

INTRODUCTION Completion of tables in the document

BLOCK I - LOCAL CONDITIONS GOVERNING THE SCREENING PROCESS Table 1.1: Baseline conditions at the start of a breast screening programme Table 1.2: Screening programme in the national context Table 1.3: Breast cancer occurrence, rates per 100,000 women per year . . Table 1.4: Registers available in the screening region/country Table 1.5: Programme promotion Table 1.6: Fees paid for the initial screening examination Table 1.7: Potential conditions for/against screening

BLOCK II - INVITATION SCHEME Table 11.1: Sources and accuracy of target population data (first round) Table II.2: Mode of invitation (INITIAL screening) Table II.3: Mode of invitation (SUBSEQUENT screening) Table II.4: Potential adjustments (INITIAL screening) Table II.5: Potential adjustments (SUBSEQUENT screening) Table II.6: Migration in and out of the screening region

BLOCK III - SCREENING PROCESS AND FURTHER ASSESSMENT Table III.1: Screening facilities and screening policy Table III.2A: Screening outcomes (INITIAL screening) Table III.2B: Screening outcomes: non-invasive investigations (INITIAL screening) Table III.2C: Screening outcomes: invasive investigations (INITIAL screening) Table III.3A: Screening outcomes (SUBSEQUENT screening) Table III.3B: Screening outcomes: non-invasive investigations (SUBSEQUENT screening) Table III.3C: Screening outcomes: invasive investigations (SUBSEQUENT screening) . . .

BLOCK IV - EVALUATION / OUTCOMES OF SCREENING Table IV. 1: Adherence to the screening programme Table IV.2: Parameters by which the performance of a B.S.P is assessed1 - INITIAL screening . . . Table IV.3: Parameters by which the performance of a B.S.P. is assessed1 - SUBSEQU. screening Table IV.4: Cancer detection rates: age-specific detection ratios per 5-year age category Table IV.5: P.P.V. of specific interventions, age category 50-64 (INITIAL screening) Table IV.6: P.P.V. of specific interventions, age category 50-64 (SUBSEQUENT screening) Table IV.7: Sensitivity and specificity of the screening test

BLOCK V - DISEASE STAGE OF SCREEN-DETECTED CANCERS Table V.1A: Size and nodal status of screen-detected cancers (INITIAL screening) Table V.1B: Disease stage according to the TNM-classification (INITIAL screening) Table V.2A: Size and nodal status of screen-detected cancers (SUBSEQUENT screening) . Table V.2B: Disease stage according to the TNM-classification (SUBSEQUENT screening)


DCK VI - TREATMENT OF SCREEN-DETECTED CANCERS 32 Table VI. 1: Treatment of screen-detected ductal CIS breast cancer 32 Table VI.2: Treatment of screen-detected invasive breast cancers according to age at diagnosis 33 Table VI.3: Treatment of screen-detected breast cancers according to stage at diagnosis 34 Table VI.4: Treatment of Breast Cancer diagnosed outside screening according to stage at diagnosis

(OPTIONAL) 35 Table VI.5: Number of days between screening and surgery or screening and final assessment (age group

50 - 64 years) for screen-detected cancers 36

DCK VII - FOLLOW UP AND ASCERTAINMENT OF INTERVAL CANCERS 37 Table VII. 1: Methods of follow up of the total target population 37 Suggested classification of interval cancers: 38 Table VII.2: Interval cancers occurring in the 12 months after previous screening 38 Table VII.3: Interval cancers occurring in the 24 months after previous screening 39 Table VII.4: Screen-detected cancers at subsequent screens (OPTIONAL) 39

DCK VIII - IMPACT ON BREAST CANCER MORTALITY 40

KNOWLEDGEMENTS 41

DSSARY OF TERMS 42


Introduction

A breast cancer screening programme is, of necessity, a multidisciplinary undertaking. The effectiveness of any programme will be directly related to the quality of the individual parts. Success will be judged, not only on the outcome of the programme and its impact on public health, but also on the organisation, implementation, execution and acceptability of the programme.

Epidemiology is the fundamental guiding and unifying discipline throughout the entire process of a screening programme, from the organisational and administrative aspects, through implementation and execution to evaluation and assessment of impact.

The organisational aspects of a screening programme include (a) identification of the source(s) of data upon which to base decisions regarding the population to be screened, (b) access to essential demographic and personal details required for the invitation to screening, administration and scheduling of the screening process, (c) dissemination of promotional information regarding screening and (d) attention to the problem of noncompliance. Additional organisational aspects include the dissemination of the results of screening to participants and appropriate professional staff, maintenance of up-to-date administrative records and the necessary periodic revisions to screening registers. It is essential to have epidemiological input into the decisions made in respect of each of these elements, since evaluation of the outcome and interpretation of the eventual results of the screening endeavour will be intimately effected by organisational aspects of the programme. Blocks I and II of this document are aimed at gaining insight into the organisational aspects of a breast screening programme.

Implementation of a breast screening programme from an epidemiological perspective entails more than simply the execution of the screening process and onward referral for assessment where required. The particular epidemiological concerns at this phase focus on the complete and accurate recording of all data pertaining to the participant, the screening test, the outcome of that test, the decisions made as a consequence and their eventual outcome in terms of diagnosis. A fundamental concern at each step is the issue of quality assurance. The success of the entire screening programme will be affected by the quality of every element of the process. Stringent quality control is therefore an integral part of each component, from the performance of the screening test (both operator and machine-dependent aspects), to interpretation of the investigation, to classification of findings and recording of results in a standardised manner. To this end Block III provides detailed guidelines to the data which should be recorded.

The evaluation of a breast screening programme is an epidemiological undertaking of paramount importance, the components of which are outlined in Block IV. Parameters of performance which describe the process of screening, and early outcomes of screening are measures of programme quality which become available early in the lifetime of a screening programme (Blocks IV, V and VI). However, it will not be possible to calculate these endpoints unless adequate provision has been made in the planning process for the complete and accurate recording of the data required. A key component of the evaluation of screening is the ascertainment of interval cancers (Block VII), a process which requires forward planning and formal links with data sources other than those required for screening. Finally, the ultimate decision regarding the effectiveness of screening, i.e. its impact on mortality and life-years gained, demands that follow-up of the screened population continues over an extended period of time, that information regarding vital status and disease-free status be ascertained and recorded at defined intervals, and that determination of programme impact be based on sound epidemiological evidence (Block VIII).

It was, therefore, deemed necessary to develop guidelines for Quality Assurance of the epidemiological aspects of screening for breast cancer. With this in mind the Breast Cancer Screening Pilot Network of the "Europe Against Cancer" programme established a working group of epidemiologists at its annual

π - Α - 1


meeting in 1994. The remit of this group was:

(a) to define a functional data set, including tables, for recording organisational aspects and results of a breast screening programme; and

(b) to draw up an accompanying list of definitions of epidemiological concepts.

Countries represented in the working group were Greece (A. Linos), Ireland (M. Codd), The Netherlands (M. Broeders, Α. Verbeek) and Spain (N. Ascunce) with C. De Wolf (E.C.) as facilitator.

These guidelines are not intended as hard and fast rules for the conduct of a screening programme. The context of screening programmes in regions and/or countries differ, for example the prior existence of a population register facilitates the issuing of personalised invitations, whereas without a population register recruitment may be by open invitation. These potential contextual differences are acknowledged in the recording of Blocks I and II; many of them will explain the outcomes entered in further tables. Since the tables are designed to accommodate breast screening programmes regardless of context, not all elements of all tables can be completed by all programmes. The working group would therefore urge caution in making strict comparisons between programmes on the basis of data in the tables, and emphasise that the reasons for these guidelines is not so much comparison as standardisation of terminology, definitions and classifications. The guidelines may further prove to be of value for new (pilot) breast screening programmes and pilot breast screening programmes in the process of extending to national programmes.

Completion of tables in the document

When absolute numbers are requested in the tables, the numbers should always reflect numbers of women (not breasts). It is possible however that a woman presents with two lesions suspected for malignancy. In this situation, data should be recorded in the tables with respect to the worst diagnosis or the most invasive diagnostic technique used. In case two breast malignancies are diagnosed, the following order of ranking should be used:

distant metastases > positive axillary lymph nodes > size of the tumour > invasive carcinoma > ductal carcinoma in situ (DCIS).

Throughout the document, data are generally requested separately for women attending an initial screening examination (initial screening) or any screening examination following an initial screening examination (subsequent screening). The terms 'initial' and 'subsequent' thus refer to individual women regardless of the screening round in which they were screened. Only the first screening examination will completely consist of women attending for a initial and subsequent screening examinations; all other screening rounds will constitute a mix of women attending for initial and subsequent screening examinations. Further, the results regarding a woman attending her first screening examination in the screening programme, should be regarded as "initial" screening data, regardless of previous invitations or reminders from the programme that the women may have received.

For purposes of comparability, the last column in a number of tables has been confined to processes and outcomes in the 50-64 year old age group. Women aged 65 at the time of screening should be excluded from these analyses. A parallel exclusion is to be made for all five-year age categories in the tables.

I I - A - 2


Block I - Local conditions governing the screening process

The aim of this block is to describe the situation at the start of a breast screening programme, i.e. the context in which it is to be or has been established.

Table 1.1 documents baseline conditions with respect to a screening programme. The availability and the reliability of data on the target population will depend on the existence and accessibility of registers in the region to be screened. Demographic data on the target population can come from various sources, e.g. census data, population registers, electoral registers, population surveys, health care data or health insurance data. For a screening programme to be population-based, every member of the target population who is eligible to attend (on the basis of pre-decided criteria) must be known to the programme. The target population of the programme can be a fixed or a dynamic cohort, which will influence the denominator used in calculating screening outcomes. In some areas, opportunistic screening may be widespread and possibly dilute the results of a breast screening programme. Please provide your best estimate of the percentage of your target population that is undergoing screening mammography (coverage) outside your breast screening programme.

Table 1.1 : Baseline conditions at the start of a breast screening programme

Name of region / country

Year that the programme started

Age group targeted

Target population*

Sources of demographic data*

Population-based*

Type of cohort (target population)

Proportion of target population covered by opportunistic screening* (%)

n =

yes/no

fixed cohort*/dynamic cohort*

* cf Glossary of terms

Table I.2 A screening programme may exist as part of a national breast screening programme, it may be one of several pilot projects for breast cancer screening or it may be the only breast screening project in existence in a country at a certain point in time. To understand the context of your screening programme, please describe its role on a national level. Please also provide your best estimate of the proportion of the national target population that is covered by breast screening programmes or by opportunistic screening. Table I.2: Screening programme in the national context

Proportion of national target population covered by breast screening programmes (%)

Proportion of national target population covered by opportunistic screening (%)

II - A - 3


Table 1.3 outlines the background information on breast cancer occurrence in the target population required to interpret outcome measures of a screening programme. If regional incidence and/or mortality data are not available, specify the area for which data are presented.

Table 1.3: Breast cancer occurrence, rates per 100,000 women per year

Breast cancer incidence in 19 ...

45-49

50-54

55-59

60-64

65-69

Breast cancer mortality in 19 ...

45-49

50-54

55-59

60-64

65-69

Sources of data on breast cancer occurrence

Area for which data on breast cancer are specified

Carcinoma in situ included in incidence rates: - ductal carcinoma in situ - lobular carcinoma in situ

Carcinoma in situ included in mortality rates: - ductal carcinoma in situ - lobular carcinoma in situ

World age-standardised incidence rate* in 19 ..., all ages

World age-standardised incidence rate* in 19 ..., 50-64

World age-standardised mortality rate* in 19 ..., all ages

World age-standardised mortality rate* in 19 ..., 50-64

/100.000

/100,000

/100.000

/100.000

/100.000

n =

n =

n =

n =

n =

/100.000

/100.000

/100.000

/100.000

/100.000

n =

n =

n =

n =

n =

yes / no yes / no

yes / no yes / no


Incidence and mortality rates are requested for women aged 45-69 in five-year age categories. For purposes of comparability, world standardised mortality and incidence rates for all ages and for the age category 50-64 should also be provided. Data on the occurrence of breast cancer may come from vital statistics registers, cancer registers, review of death certificates, etc. In this respect, it is of interest to specify whether carcinomas in situ are included in breast cancer incidence and mortality rates.

π - A - 4


Table 1.4 specifies which of the registers listed are present in the screening region or country, details whether they are hospital- or population-based, and whether they are accessible to members of screening programme staff.

Table 1.4: Registers available in the screening region/country

Cancer register

Pathology register

Breast cancer register*

Present yes/no

Regional/National (R) (N)

Hospital (HB) or Pop.based (PB)

Accessible yes/no


Table 1.5 refers to a variety of modes potentially available to publicise the screening programme. Depending on the target population and the local geographical, municipal and cultural conditions, the need and intensity of programme promotion may vary. Please indicate the intensity of the activities that are used in your screening programme, using a scale of 10 (for the most intensive) to 1 (for the least intensive). Use '0' when a particular mode is not available or not used at all.

Table 1.5: Programme promotion

Press

TV

Radio

Physician/GP

Church

Schools

Municipal authorities

Social clubs

Other:

I I - A - 5


Table I.6 A potential determinant of participation in a breast screening programme is whether the participating woman is required to pay for the initial screening examination. When a consultation with a family practitioner is required to gain access to the initial screening examination, the costs of this consultation should be included in the fee paid. In some screening programmes, the fee for the screening examination will be paid, partly or completely, by a third party. Third party payment may be either through vouchers available to the woman before screening or through a system in which the woman pays in advance and gets reimbursed after the screening. Alternatively, a third party may pay the fee directly to the screening unit or organisation.

Table 1.6: Fees paid for the initial screening examination

Fees paid by the woman herself for the screening examination (in ECU's)

Fees paid by the woman herself to receive the results (in ECU's)

Third party payment through voucher(s)

Third party payment through reimbursement system

Third party payment directly to screening unit

% of costs covered

% of costs covered

% of costs covered

Table 1.7 Many factors can be identified which encourage or impede the setting up of a breast screening programme. The following are such potential factors: costs, fears, lack of interest, integration into the existing health care system, data protection legislation. These can also include reasons given for not responding to the invitation to be screened, and women's attitudes about and knowledge of screening guidelines.

Table I.7: Potential conditions for/against screening

Please specify any conditions that may have worked for or against screening in your screening programme:

I I - A - 6


Block II - Invitation scheme

The aim of this block is to describe the invitation scheme used by a screening programme, i.e. the processes used to identify and personally invite members of the target population. A number of sources of data can be used. For each source, information is requested regarding its accuracy.

Table 11.1 lists the sources of demographic data used and the contribution of each to the identification of the target population in preparation for the first screening round. It is recognised that relative contributions of these sources will vary and may be difficult to estimate.

Table 11.1: Sources and accuracy of target population data (first round)

Population register

Electoral register

Organisation register*

Self-registration*

Health insurance

Church register

Other:

% Target population identified

Register accuracy (%)

Register data Computer/Handhold

cf Glossary of terms

I I - A - 7


Table II.2 Depending on the programme several types of initial call systems may be used. Invitations may be by personalised letter, by oral communication or by open invitation, or by a combination of all three. Those who do not respond to the initial invitation may be issued a reminder, again by any available means listed below. The time interval (column 5) between initial invitation and reminder will vary by programme. Some programmes may issue more than one reminder, or reminders by multiple methods. It may not be possible to ascertain the success of individual types of reminders.

Table II.2: Mode of invitation (INITIAL screening)

Option

LETTER

ORAL/ TELEPHONE

OPEN

Method

by mail

at physician/GP

by community leader

other

physician/GP

community leader

municipal officers

screening unit

public health nurse

teachers

priests

other

public announcement

Initial invitation Reminder Interval to reminder

ORGANISATIONAL:

► If the initial invitation is by mail, does the letter provide an appointment for a fixed date and time? Yes / No

► If the letter provides a fixed appointment, is the woman offered an opportunity to change the appointment? Yes / No

I I - A ·


Table II.3 details the same information on the invitation scheme for subsequent screening examinations.

Table II.3: Mode of invitation (SUBSEQUENT screening)

Option

LETTER

ORAL/ TELEPHONE

OPEN

Method

by mail

at physician/GP

by community leader

other

physician/GP

community leader

municipal officers

screening unit

public health nurse

teachers

priests

other

public announcement

Initial invitation Reminder Interval to reminder

ORGANISATIONAL:

► If the initial invitation is by mail, does the letter provide an appointment for a fixed date and time? Yes / No

► If the letter provides a fixed appointment, is the woman offered an opportunity to change the appointment? Yes / No

I I - A - 9


Table II.4 and II.5 In the context of this document, the target population for the breast screening programme includes all persons eligible to attend for screening on the basis of age, gender and geographic location. However, each programme may identify additional criteria on the basis of which women will be excluded from the target population. The remaining group after adjustment will be referred to as the 'eligible population'. In addition, screening programmes may identify criteria to exclude women from the results of screening. Potential exclusions from both the target population and results of screening are listed in table II.4 (initial screening examination) and II.5 (subsequent screening examination). The ease with which such individuals can be identified and excluded from the target population will vary by programme; for some programmes it may not be possible to identify any category of potential exclusion prior to invitation.

Table II.4: Potential adjustments (INITIAL screening)

Target population

Eligible population

Previous breast cancer

Previous mastectomy - unilateral - bilateral

Recent mammogram*

Symptomatic women*

Incompetent - physical - mental - other

Deaths

Other, please specify:

n =

n =

Excluded from target population yes/no

Number if known

Excluded from results yes/no

Number if known


II - A -10


Table II.5: Potential adjustments (SUBSEQUENT screening)

Target population

Eligible population

Previous breast cancer

Previous mastectomy - unilateral - bilateral

Recent mammogram*

Symptomatic women*

Incompetent - physical - mental - other

Deaths

Other, please specify:

n =

n =

Excluded from target population yes/no

Number if known

Excluded from results yes/no

Number if known


Table II.6 Each screening programme is confronted with women moving in and out of the region and thus moving in and out of the target population. Please describe how your screening programme is dealing with migration and, if possible, provide your best estimate of the number of women concerned.

Table II.6: Migration in and out of the screening region

I I - A -


Block III - Screening process and further assessment

The aim of this block is to describe the process of mammographie detection of breast abnormalities through investigation of those abnormalities, to diagnosis or otherwise of a malignant lesion.

Table III.1 describes the screening facilities available and whether they are dedicated completely to breast cancer screening. Further details on screening policy of the programme are requested such as: the screening test used (whether single or two-view mammography, with or without clinical examination), the interval between screens, the availability of double reading, and the assessment facilities for invasive investigations (centralised or not).

Table III.1: Screening facilities and screening policy

Screening units* - static units - semi-mobile units - mobile units - other

Number of mammography machines

Screening test* - initial screening - subsequent screening

Screening interval*

Double reading

Centralised assessment (refers to invasive investigations only)

n = , dedicated* n = n = , dedicated* η = η = , dedicated* η = η = , dedicated* η =

η = , dedicated* η =

yes/no


Table III.2 describes the outcomes of initial screening examinations, as well as the additional investigations which may be undertaken prior to, and including surgery. Initial screening examinations refer to women who undergo their first screening examination within the screening programme, regardless of the organisational screening round in which they are screened and regardless of previous invitations or reminders. The order of investigations as listed does not necessarily imply that each participant will go through all stages before surgical excision and diagnosis. The table is designed to introduce some standardisation and comparability of data between programmes. Forali investigations listed the numbers should reflect women, not breasts. The age category in which the result of an individual woman should be recorded is to be defined according to the age of the woman at the time of the relevant activity, e.g. age of a women at invitation, age of a woman at the time of the screening examination. It is thus possible, that a woman's results will be recorded in different age categories at different points in the screening process.

I I - A - 12


Table III.2A lists the number of women that are targeted, eligible, invited and finally screened. The result of the screening examination can be recorded in various categories, that may not all be available in the screening programme, e.g. a screening programme may not have the option of intermediate mammography directly following the screening examination. Further assessment includes non-invasive and invasive investigations for medical reasons.

Table III.2A: Screening outcomes (INITIAL screening)

Target population*

Eligible population*

Women invited*

Women screened*

Result of screening test - negative - intermediate

mammogram following screening*

- repeat screening test*

- recommended - performed

- further assessment*


- unknown/not available

45-49 50-54 55-59 60-64 65-69 age unk. 50-64

*cf Glossary of terms

I I - A - 1 3


Table III.2B describes the outcomes of non-invasive investigations directly following the screening examination. These investigations can be done at the time of screening when facilities are available in the screening unit or they can be performed on recall, i.e. the woman will have to come back to the screening unit for that extra examination. As a result of the non-invasive assessment, further clarification of the perceived abnormality may be required using invasive investigations. It should be realised however, that a woman may also undergo further assessment by invasive investigations directly following the screening examination.

Table III.2B: Screening outcomes: non-invasive investigations (INITIAL screening)

Repeat screening test* - at the time of

screening - done on recall*

Further assessment by additional imaging - at the time of

screening - done on recall*

Types of additional imaging - repeat views for

medical reasons - cranio-caudal view - other views - ultrasound - MRI

Further assessment by invasive investigations - recommended - performed

- at the time of screening

- done on recall*

45-49 50-54 55-59 60-64 65-69 age unk. 50-64


I I - A - 14


Table III.2C describes the numbers of recommended and/or performed invasive investigations. The results of the overall screening process are classified in four categories, partly overlapping the results of the screening test in table III.2A.

Table III.2C: Screening outcomes: invasive investigations (INITIAL screening)

Cytology* - recommended - performed Core biopsy* - recommended - performed Open biopsy* - recommended - performed

Result of screening process: - negative - intermediate mammog.

required following: - screening*, including repeat screening tests - further assessment*

- malignant tumours detected:

-DCIS - invasive cancers


Malignant tumours detected: - at routine screen - at intermediate

mammography*

45-49 50-54 55-59 60-64 65-69 age unk. 50-64


ORGANISATIONAL:

To which organisational screening rounds and time period do the data in tables III.2A, Β and C refer?

Time period:

Organisational

screening rounds:

I I - A - 15


Table III.3 requests the same information as table III.2 but for subsequent screening examinations. Subsequent screening examinations refer to all examinations of individual women within the screening programme following initial screening, regardless of the organisational screening round in which they are screened.

Table III.3A: Screening outcomes (SUBSEQUENT screening)

Target population*

Eligible population*

Women invited*

Women screened*

Result of screening test - negative - intermediate

mammogram following screening*

- repeat screening test*


- further assessment* - recommended - performed


45-49 50-54 55-59 60-64 65-69 age unk. 50-64


II - A - 16


Table III.3B: Screening outcomes: non-invasive investigations (SUBSEQUENT screening)

Repeat screening test* - at the time of screening - done on recall*

Further assessment by additional imaging - at the time of screening - done on recall*

Types of additional imaging - repeat views for medical

reasons - cranio-caudal view - other views - ultrasound -MRI

Further assessment by invasive investigations - recommended - performed

- at the time of screening - done on recall*

45-49 50-54 55-59 60-64 65-69 age unk. 50-64


ORGANISATIONAL:

To which organisational screening rounds and time period do the data in tables III.3A, Β and C refer?

Time period:

Organisational

screening rounds:

I I - A - 17


Table III.3C: Screening outcomes: invasive investigations (SUBSEQUENT screening)

Cytology* - recommended - performed Core biopsy* - recommended - performed Open biopsy* - recommended - performed

Result of screening process: - negative - intermediate Mammogr.

required following: - screening*, including

repeat screening tests - further assessment*

- malignant tumours detected:

-DCIS - invasive cancers


Malignant tumours detected: - at routine screen - at intermediate

mammography*

45-49 50-54 55-59 60-64 65-69 age unk. 50-64


II - A - 1Í


Block IV - Evaluation / outcomes of screening

Evaluating the outcome of a screening programme requires considerable input from epidemiology and statistics. The indicators of performance of interest are as follows (for definitions see Glossary of terms):

PROCESS EVALUATION - participation rate - additional imaging rate - recall rate - cancer detection rate - specificity - positive predictive value

EARLY OUTCOMES - surgical procedures performed - benign / malignant biopsy ratio - invasive cancers < 10 mm in diameter - stage at diagnosis - ascertainment of interval cancers - sensitivity

LATE OUTCOMES - case fatality rate - mortality rates (relative and absolute)

PROGRAMME IMPACT - deaths prevented - life years gained -quality of life - side effects - cost-effectiveness

Results of a screening programme become available throughout the screening process and afterwards. Information on participation, recall and cancer detection rates will be available at the end of a screening round. If one accepts certain assumptions, estimates of specificity and positive (but not negative) predictive value can also be derived at the end of a round. If surgical and pathological data are complete, information on surgical procedures, size and types of cancers and on stage at diagnosis will also be available.

Ascertainment of interval cancers, and consequently estimates of sensitivity and negative predictive value, cannot be complete until a specified interval since the last women were screened has passed. This is usually 24 months.

Assessment of late outcomes and impact of the programme takes many years to complete.

Table IV.1 In the evaluation of a breast screening programme, participation is the key indicator which predicts the overall capacity of the programme to ultimately reduce breast cancer mortality. However, for these programmes to be really effective, not only the overall participation should be evaluated but also the adherence to the programme shown by women in later screening rounds. Adherence to the screening programme can be expressed as the percentage of women in the current screening round who also attended the previous screening round.

I I - A - 19


Table IV.1 : Adherence to the screening programme

Participation in previous screening round

Participation in current screening round

YES

NO

n=

n=

YES

A

C

n=

n=

NO

Β

D

ADHERENCE = A/ (A+C) =

Table IV.2 and IV.3 In keeping with the staged nature of the availability of outcome measures, the Europe Against Cancer Programme has outlined those parameters of performance which can be assessed in the early stages of a programme to provide a yardstick. In comparison to the performance parameters introduced in first edition of the European Guidelines for Quality Assurance in Mammography Screening, the following parameters have been added:

(a) participation rate

(b) additional imaging at the time of screening (to be expressed as a percentage of all women undergoing a screening examination)

(c) total additional imaging procedures, i.e. additional imaging at the time of screening or on recall (to be expressed as a percentage of all women undergoing a screening examination)

(d) cytology/biopsy procedures with an inadequate result (to be expressed as a percentage of all cytology/biopsy procedures performed). This parameter is a measure of operator competence and quality of selection of lesions for sampling.

II - A - 20


Table IV.2 and IV.3 show the acceptable and desirable levels for a number of the above-mentioned parameters of performance for initial and subsequent screening examinations. Outcomes from your screening programme for the age category 50-64 should be entered in the last column.

ORGANISATIONAL: To which organisational screening rounds and time period do the data in Block IV refer?

Time period:

Organisational screening rounds:

Table IV.2: Parameters by which the performance of a Breast Screening Programme is assessed -INITIAL screening

Performance parameter

Participation rate

Additional imaging - at the time of screening - total

Recall rate

Cytology/biopsy procedures with an inadequate result (%)

Total cancer detection rate (per 1000 women screened)***

- invasive cancer detection rate - in-situ cancer detection rate

Invasive cancers s 10 mm diameter (% of inv. cancers detected)

Benign open biopsy rate (per 1000 women screened)

Benign to malignant biopsy ratio

Acceptable

60%

<5% NG*

<7%

< 25%

3xlR**

NG*

<5

< 2 to 1

Desirable

> 75%

< 1% NG*

<5%

<15%

>3xlR**

25%

<4

<1 to 1

Screening programme

50-64

NG = none given IR = expected incidence rate in the absence of screening The cancer detection rate per five-year age category is further specified in table IV.4.

II - A -21


Table IV.3: Parameters by which the performance of a Breast Screening Programme is assessed SUBSEQUENT screening

Performance parameter

Participation rate

Additional imaging - at the time of screening - total

Recall rate

Cytology/biopsy procedures with an inadequate result (%)

Total cancer detection rate (per 1000 women screened)***

- invasive cancer detection rate - in-situ cancer detection rate

Invasive cancers, s 10 mm diameter (% of inv. cancers detected)

Benign open biopsy rate (per 1000 women screened)

Benign to malignant biopsy ratio

Acceptable

60%

<3% NG*

<5%

< 25%

1,5x1 R**

NG*

<3,5

< 1 to 1

Desirable

> 75%

< 1 % NG*

<3%

< 15%

NG*

25%

<2

< 0,5 to 1

Screening programme

50-64

NG = none given IR = expected incidence rate in the absence of screening The cancer detection rate per five-year age category is further specified in table IV.4.

π - A - 22


Table IV.4 An overall breast cancer detection rate represents the performance of a screening programme but also reflects the age structure of the population being screened. To provide a more sensitive measure of performance, table IV.4 allows for the calculation of age-specific detection ratios per 5-year age category. The incidence rate for breast cancer in the denominator of the formula should reflect the incidence rate in the year before screening started.

Age-specific Detection Ratio = Cancer detection rate in a 5-year age category

Breast cancer incidence in that age category in the year before screening started

Table IV.4: Cancer detection rates: age-specific detection ratios per 5-year age category

Age category

45-49

50-54

55-59

60-64

65-69

Initial screening

CDR BCI ADR

Subsequent screening

CDR BCI ADR

CDR = Cancer detection rate (nominator) BCI = Breast cancer incidence (denominator) ADR = Age-specific Detection Ratio = CDR/BCI

II - A - 23


Table IV.5 and IV.6 summarise the results of screening in terms of positive predictive values (PPV) of specific interventions which take place in the course of mammographie screening and in further assessment of abnormal lesions. Results can be expected to vary between initial and subsequent screening examinations. PPV is expressed as a proportion. (See Glossary of terms for definition of the individual PPV's listed in Table IV.5 and IV.6)

Table IV.5: Positive Predictive Values of specific interventions in screening for breast cancer, age category 50-64 (INITIAL screening)

Outcome of the intervention

screening test positive

negative

additional imaging positive

negative

recall yes

no

cytology positive

negative

recommendation for positive open biopsy

negative

Breast cancer detected

yes no

Positive Predictive Value

POSITIVE PREDICTIVE VALUE = A / (A+B)

Breast cancer

Intervention A

C

Β

D

A + C B + D

A + B

C + D

Ν

II - A - 24


Table IV.6: Positive Predictive Values of specific interventions in screening for breast cancer, age category 50-64 (SUBSEQUENT screening)

Outcome of the intervention

screening test positive

negative

additional imaging positive

negative

recall yes

no

cytology positive

negative

recommendation for positive open biopsy

negative

Breast cancer detected

yes no

Positive Predictive Value

POSITIVE PREDICTIVE VALUE = A / (A+B)

Breast cancer

Intervention A

C

Β

D

A + C B + D

A + B

C + D

Ν

I I - A - 2 5


Table IV.7 A screening test is expected to designate persons with early malignant disease as 'positive' (sensitivity of the test) and those without as 'negative' (specificity of the test). An acceptable way of estimating the sensitivity is to follow up the negative screenees for the development of cancer within a defined time interval. If these interval cancer cases are assumed to have been falsely negative, the sensitivity can be assessed by relating these interval cancers to the number of cancers detected (true positives / true positive + false negatives) (1). To evaluate the specificity of the screening test, it is necessary to know the numbers of false positives. Assessment of specificity again requires adequate follow up of the negative screenees. It has been shown however that it is possible to give a close approximation of the specificity without knowledge of the number of missed cancers. The specificity can thus reliably be estimated soon after the start of the screening programme. The specificity relates to the number of true negatives to the total number of 'non-cancer' women. Under the rare disease assumption the specificity is defined as: screening test negatives / (screened women - true positives)(2).

Table IV.7: Sensitivity and specificity of the screening test

Breast cancer

Screeningtest + A Β A + B

C + D

A + C B + D Ν

SENSITIVITY = A / (A+C) =

SPECIFICITY = D/(B+D) =

APPROXIMATION OF = (C+D) / (N-A) = SPECIFICITY

REFERENCES 1 Verbeek ALM. Population screening for breast cancer in Nijmegen; an evaluation of the period 1975-1982 (thesis). Univ. of

Nijmegen. 1985 2 Verbeek ALM, van den Ban MC, Hendriks JHCL. A proposal for short-term quality control in breast cancer screening. Br J

Cancer 1991:63:261-264

A

C

Β

D

II - A - 26


edition (JUNE 1996)

Block V - Disease stage of screen-detected cancers

The aim of this block is to describe the disease stage of screen-detected cancer cases. A prerequisite for

a reduction in breast cancer mortality is a more favourable stage distribution in screen-detected cancers

compared with clinically diagnosed cancers. Tumour size and axillary lymph node involvement for invasive

cancers are of central importance here, and are assessed preferably after surgery (pT and pN). Age

categories in Block V all refer to the age of a woman at diagnosis. Diagnosis refers to the day of surgery

for women undergoing surgery and to the day of final assessment for women not undergoing surgery.

The categorisation for size according to pathological diameter is based on the TNM-classification for

reasons of comparison. It is recommended however to register the size of the tumour on a continuous

scale. This will allow for re-categorisation in the event that consensus is reached on a different prognostic

threshold (e.g. 15 mm).

Primary tumour (T) is classified as follows:

pTx primary tumour cannot be assessed

pTO no evidence of primary tumour

pTis ductal carcinoma in situ

pT1ab tumour Ú 10 mm in greatest dimension

pT1c tumour s 20 mm in greatest dimension

pT2 tumour s 50 mm in greatest dimension

pT3 tumour > 50 mm in greatest dimension

pT4 tumour of any size with direct extension to chest wall or skin

Regional lymph node involvement (N) is classified as follows:

Nx regional lymph nodes cannot be assessed

NO no regional lymph node metastasis

N1 metastasis to movable ipsilateral axillary lymph node(s)

N2 metastasis to ipsilateral axillary lymph node(s) fixed to one another or to other

structures

N3 metastasis to ipsilateral mammary lymph node(s)

Distant metastasis (M) is classified as follows:

Mx presence of distant metastasis cannot be assessed

MO no distant metastasis

M1 distant metastasis (includes metastasis to ipsilateral supraclavicular lymph node(s)

Stage grouping

Stage 0

Stage I

Stage IIA

Stage MB

Stage IMA

Stage HIB

Stage IV

Tis

T1

TO

T1

T2

T2

T3

TO

T1

T2

T3

T3

T4

any Τ

any Τ

NO

NO

N1

N1

NO

N1

NO

N2

N2

N2

N1

N2

any Ν

N3

any Ν

MO

MO

MO

MO

MO

MO

MO

MO

MO

MO

MO

MO

MO

MO

M1

I I - A - 2 7


ORGANISATIONAL:

To which organisational screening rounds and time period do the data in tables V.1 and V.2 refer?

Time period:

Organisational

screening rounds:

Table V.1 A: Size and nodal status of screen-detected cancers (INITIAL screening)

pTis

pT1ab N-N+ Nx

pT1c N-N+ Nx

pT2 N-N+ Nx

pT3 N-N+ Nx

pT4 N-N+ Nx

pTx N-N+ Nx

TOTAL N-N+ Nx

45-49 50-54 55-59 60-64 65-69 age unknown 50-64

N- = axillary node negative (NO) N+ = axillary node positive (any node positive; N1-3) Nx = nodal status cannot be assessed (e.g. previously removed, not done)

I I - A - 2 8


Table V.1 B: Disease stage of screen-detected cancers according to the TNM-classification (INITIAL screening)

Stage 0 TisNOMO

Stage I T1N0M0

Stage IIA T1N1M0 T2N0M0

Stage IIB T2N1M0 T3N0M0

Stage INA T1N2M0 T2N2M0 T3N1M0

T3N2M 0

Stage NIB T4anyNM0 anyTN3M0

Stage IV anyTanyNMI

Unknown

TOTAL

45-49 50-54 55-59 60-64 65-69 age unknown 50-64

II - A - 29


Table V.2A: Size and nodal status of screen-detected cancers (SUBSEQUENT screening)

pTis

pT1ab N-N+ Nx

pT1c N-N+ Nx

pT2 N-N+ Nx

pT3 N-N+ Nx

pT4 N-N+ Nx

pTx N-N+ Nx

TOTAL N-N+ Nx

45-49 50-54 55-59 60-64 65-69 age unknown 50-64

N- = axillary node negative (NO) N+ = axillary node positive (any node positive; N1-3) Nx = nodal status cannot be assessed (e.g. previously removed, not done)

I I - A - 3 0


Table V.2B: Disease stage of screen-detected cancers according to the TNM-classification (SUBSEQUENT screening)

Stage 0 TisNOMO

Stage I T1N0M0

Stage IIA T1N1M0 T2N0M0

Stage MB T2N1M0 T3N0M0

Stage IMA T1N2M0 T2N2M0 T3N1M0 T3N2M0

Stage NIB T4anyNM0 anyTN3M0

Stage IV anyTanyNMI

Unknown

TOTAL

45-49 50-54 55-59 60-64 65-69 age unknown 50-64

II - A - 31


Block VI - Treatment of screen-detected cancers

It is recognised that collecting data on treatment on a regular basis may be a difficult and time consuming activity, especially in those screening programmes where treatment is not considered to be part of the screening process. On the other hand, it should be realised that the effect of screening in the long term will be heavily influenced by the way screen-detected cases are treated. A high-quality screening programme can only lead to a long-term mortality reduction if the treatment of women detected at screening is of equally high quality. Thus it is considered of the utmost importance to collect these type of data.

All women with breast cancer detected at screening, with or without signs of distant metastases, will receive a form of primary treatment. For ductal carcinoma in situ (CIS) and invasive cancers several types of treatment are categorised in tables VI.1, VI.2 and VI.3. Women with axillary lymph node metastases are assumed to receive adjuvant systemic therapy. The treatment options according to disease stage of breast cancer diagnosed outside screening (interval cancer as well as other 'control' cancers) can be optionally registered in table VI.4.

Table VI.1: Treatment of screen-detected ductal CIS breast cancer

45-49

50-54

55-59

60-64

65-69

Unknown

50-64

Breast conserving surgery1

RT- RT+ RTx

Mastectomy Remaining2

' = less than amputation 2 = treatment refusal or (still) unknown RT- = without radiotherapy RT+ = with radiotherapy RTx = unknown

I I - A - 3 2

Table VI.2:

45-49

50-54

55-59

60-64

65-69

Unkn.

50-64

45-49

50-54

55-59

60-64

65-69

50-64

Treatment of screer i-detected invasive breast cancers according to age at diagnosis

PRIMARY TREATMENT

Breast conserving surgery1

RT- RT+ RTx

Mastectomy

RT- RT+ RTx

Chemotherapy

RT- RT+ RTx

Radiotherapy

Rem2

ADJUVANT THERAPY (H=hormonal therapy; C=chemotherapy; B=both therapies; N=no adjuvant therapy)

RT-

H c Β Ν

RT+

Η C Β Ν

RTx

Η C Β Ν

RT-

H C Β Ν

RT+

Η C Β Ν

RTx

Η C Β Ν

RT-

H C Β Ν

RT+

H C Β Ν

RTx

Η C Β Ν Η C Β Ν

1 = less than amputation;2 remaining = treatment refusal or (still) unknown Radiotherapy: RT- = without radiotherapy; RT+ = with radiotherapy; RTx = unknown Adjuvant therapy: Η = hormonal therapy; C = chemotherapy; Β = both therapies; Ν = no adjuvant therapy

Table VI.3:

0

ι IIA

IIB

MIA

HIB

IV

Unkn.

0

1

IIA

IIB

MIA

HIB

IV

Treatment of screer i-detected breast cancers accord ing te stage at diag nosis

PRIMARY TREATMENT

Breast conserving surgery

RT- RT+ RTx

Mastectomy

RT- RT+ RTx

Chemotherapy

RT- RT+ RTx

Radiotherapy

Rem2


RT-

H c Β Ν

RT+

Η C Β Ν

RTx

Η C Β Ν

RT-

H C Β Ν

RT+

Η C Β Ν

RTx

Η C Β Ν

RT-

H C Β Ν

RT+

Η C Β Ν

RTx


Table VI.4: Treatment of breast cancers diagnosed outside screening according to stage at diagnosis (OPTIONAL)

0

1

IIA

IIB

UIA

HIB

IV

Unkn.

0

1

IIA

IIB

IIIA

HIB

IV

PRIMARY TREATMENT

Breast conserving surgery

RT- RT+ RTx

Mastectomy

RT- RT+ RTx

Chemotherapy

RT- RT+ RTx

Radiotherapy

Rem2


RT-

H C Β Ν

RT+

Η C Β Ν

RTx

Η C Β Ν

RT-

H C Β Ν

RT+

Η C Β Ν

RTx

Η C Β Ν

RT-

Η C Β Ν

RT+

Η C Β Ν

RTx



Table VI.5 reflects the distribution of the number of days between the day of screening and the day of surgery for those women undergoing surgery as a result of the screening examination. For those women not undergoing surgery, the interval between the day of screening and the day of final assessment should be registered. In case a cancer is detected at intermediate mammography, which is by definition a screen-detected cancer, the day of screening should be replaced by the day that the intermediate mammogram was performed.

Table VI.5: Number of days between screening and surgery or screening and final assessment (age group 50 - 64 years) for screen-detected cancers

Day of screening - day of surgery

Day of screening - day of final assessment

Quantizes

5% 25% 50% 75% 95%

ORGANISATIONAL: To which organisational screening rounds and time period do the data in Block VI refer?

Time period:

Organisational screening rounds:

I I - A - 3 6


Block VII - Follow up and ascertainment of interval cancers

The aim of this block is to describe, as far as is possible, the follow up of the target population of a screening programme, including ascertainment of interval cancers.

The target population will fall essentially into four groups:

(a) women who have participated in the programme and were dismissed as having a negative screening test, or were deemed not to have a breast malignancy after further investigation of an abnormality. Follow up of this group is key to the ascertainment of interval cancers;

(b) women who have participated in the screening programme, and who were identified as having breast cancer. These patients will be followed clinically, most likely in general practitioner, surgical, oncology or radiotherapy clinics, for treatment and review of their breast cancer, including evidence of recurrence. Arguably, follow up of this group does not constitute part of a screening programme. Nonetheless, the outcome of breast screening in terms of survival, will be determined in large measure by the clinical course of patients identified with breast cancer;

(c) women who were invited for screening, but did not participate;

(d) members of the target population who were not invited for screening (e.g. due to incomplete or inaccurate population registers, etc.). It is recognised that it may not be possible to get follow up information on this group.

Table VII.1 outlines the methods by which the total target population may be followed up for the occurrence of breast cancer. In general, follow up for ascertainment of interval cancers, or cancer occurrence in non-screened members of the target population (non-participants and not invited) will require review of cancer registers, specific pathology registers or records of pathology departments of the screening ± contiguous area hospitals, and/or vital statistics/death certificates.

Table VII.1: Methods of follow up of the total target population

Method yes/no

cancer register

pathology register

death certificates

other:

Participants -Negative

Participants -Positive

Non - participants Not invited

Interval cancers (cf Glossary of terms) are a heterogeneous group of cancers, which may be classified into subgroups. The classification below, assuming mammography is the screening test applied, is based on: (a) the occurrence of a clinical breast cancer in a screened woman between two routine screens; (b) review of the screening mammogram in the knowledge that an interval cancer has occurred; and (c) the existence, or not, of a mammogram at the time of clinical presentation.

II - A - 3 7


Suggested classification of interval cancers:

Interval cancer

True interval

Radiologically occult

Minimal signs

False negative

Unclassifiable

Screening mammogram

negative

negative

positive (minimal signs)

positive

positive / negative / not available

Presenting mammogram

positive

negative

positive

positive

not available / not taken

It is recognised that a person presenting with an interval cancer may or may not have a mammogram performed on presentation. This will depend on the preference of the clinician to whom presented, as well as the availability of mammographie facilities. When a presenting mammogram has not been taken, or is unavailable, the interval cancer concerned is unclassifiable.

Table VII.2 and VII.3 contain a suggested method for recording the interval cancers (total and subtypes) which occur in a defined period following screening. It is usual to report the 12-month and/or 24-month interval cancer rate of a screening programme, per 1000 women screened. Interval cancers are to be reported according to 5-year age category and for a limited age range (i.e. 50-64 years). The age referred to in Tables VI.2 and VI.3 is the age at the time of the screening examination. When comparing interval cancer rates across screening programmes the rates should be expressed as a proportion of the underlying (expected) breast cancer incidence rate in the absence of screening.

Table VII.2: Interval cancers occurring in the 12 months after previous screening

Interval cancers

True interval


Minimal signs

False negative

Unclassifiable

TOTAL

Interval cancer rate (per 10,000 women screened)

Incidence rate expected in the absence of screening (per 10,000 women)

45-49 50-54 55-59 60-64 65-69 age unk. 50-64

II - A - 3 8


Table VII.3: Interval cancers occurring in the 24 months after previous screening

Interval cancers

True interval


Minimal signs

False negative

Unclassifiable

TOTAL

Interval cancer rate (per 10,000 women screened)

Incidence rate expected in the absence of screening (per 10,000 women)

45-49 50-54 55-59 60-64 65-69 age unk. 50-64

Table VII.4. The suggested classification of interval cancers can also be applied to cancers detected at subsequent screens, with the exception of the category 'radiologically occult' if mammography is the sole screening test. Although radiologic review of cancers mostly focuses on the group of interval cancers, further insight into the sensitivity and specificity of mammography might be obtained by studying the distribution of subtypes in screening mammograms as well as in presenting mammograms of interval cancers, and relating the outcome to diagnosis.

Table VII.4: Screen-detected cancers at subsequent screens (OPTIONAL)

Screen-detected cancers

True interval


Minimal signs

False negative

Unclassifiable

TOTAL

45-49 50-54 55-59 60-64 65-69 age unk. 50-64

not applicable

II - A - 39


edition (JUNE 1996)

Block VIM - Impact on breast cancer mortality

The ultimate objective of every screening programme for breast cancer is to impact favourably on mortality

from the disease, while not adversely affecting the health status of those who participate in the

programme. Several studies, carried out in different countries, over different time periods, using differing

epidemiological approaches, have demonstrated a beneficial effect of mammographie screening on

mortality from breast cancer (1-10).

Estimates of reduction in breast cancer mortality that have been achieved to date in randomised controlled

trials of mammographie screening vary from 4% (4) to 30% (2). Estimates of benefit from case-control

studies could be as high as 52% (8) to 70% (9). For logistic reasons, however, it is not possible for all

screening programmes to embark on a randomised controlled trial or case-control study of mammography.

Nonetheless, every programme, new and existing, will be required to make its own periodic determination

of impact on mortality. While it may be tempting to predict that a programme can achieve a reduction in

mortality of the order of the higher estimates quoted above, recent data examining non-randomised

general population screening suggest that the impact in the non-randomised situation is somewhat

reduced (11). The fore-mentioned study does point out, however, that the better organised the population

programme the more reliable will be the estimate of mortality reduction.

The prediction of mortality reduction achieved by screening has been studied (12). It has been deemed

possible to predict the level of reduction by reference to a number of items which are specific to individual

programmes, and therefore not generalisable. These include the age-specific incidence and mortality rates

from breast cancer, estimates of rates of disease progression, the sensitivity and specificity of the

screening test employed, the therapeutic efficacy of treatment, the age groups chosen for screening and

the expected compliance rate (12).

Ascertainment of impact on mortality demands (a) that follow up of the screened cohorts continues over

extended periods of time, (b) that data on vital status and disease-free interval be vigorously sought and

recorded despite the problems of follow up, and (c) that adequate links exist between programme data

and other relevant data sources, e.g. medical records, pathology registers, death certificate information.

The complexities and variation from region to region of this element of evaluation precludes a detailed

outline of the recording requirements at this time. The purpose of this narrative is to prime the

epidemiologists of new and existing programmes to the need for ongoing evaluation of the impact of

screening on breast cancer mortality.

References

1 Shapiro S, Venet W, Strax Ρ, et al. Periodic screening for breast cancer: the Health Insurance Plan project and its sequelae, 1963-1986. Baltimore, MD: Johns Hopkin University Press, 1988.

2 Tabar L, Fagerberg G, Duffy SW, et al. The Swedish two county trial of mammographie screening for breast cancer: recent

results and calculation of benefit. J Epidemiol Community Health 1989;43:107-14.

3 UK Trial of Early Detection of Breast Cancer Group. First results on mortality reduction in the UK trial of early detection of breast cancer. Lancet 1988;2:411-16.

4 Andersson I, Aspegren K, Janzon L, et al. Mammographie screening and mortality from breast cancer: the Malmö mammographie screening triai. BMJ 1988;297:943-8

5 Roberts MM, Alexander FE, Anderson TJ, et al.Edinburgh trial of screening for breast cancer: mortality at seven years. Lancet 1990;335:241-6

6 Frisell J, Eklund G, Hellstrom L, et al. Randomised trial of mammography screening - preliminary report on mortality in the

Stockholm trial. Breast Cancer Res Treat 1991;18:49-56

7 Morrison AS, Brisson J, Khalid N. Breast cancer incidence and mortality in the Breast Cancer Detection and Demonstration Project. JNCI 1988;80:1540-7

I I - A - 4 0


edition (JUNE 1996)

8 Verbeek ALM, Hendriks JHCL, Holland R, et al. Mammographie screening and breast cancer mortality: age-specific effects in Nijmegen project, 1975-1982. Lancet 1985;1:865-6

9 Collette HJA, Day NE, Rombach LL, et al. Evaluation of screening for breast cancer in a non-randomised study (the DOM Project) by means of a case-control study. Lancet 1984;1:1224-6

10 Palli D, Del Turco MR, Buaitti E, et al. A case-control study of the efficacy of a non-randomised breast cancer screening program in Florence (Italy). Int J Cancer 1986;38:501-4

11 Törnberg S, Carstensen J, Hakuinen T, Lenner Ρ, Hatschek T, Lundgren B. Evaluation of the effect on breast cancer mortality of population based mammography screening programmes. J.Med. Screening 1994;1:184-187

12 Knox EG. Evaluation of a proposed screening regimen. BMJ1988;297:650-654

Acknowledgements

The assistance of the European Commission 'Europe against Cancer' programme with Dr. Chris de Wolf

as facilitator is gratefully acknowledged. Drafts of the document were discussed and reviewed at the

annual meeting of the Pilot Network for Breast Cancer Screening in Strasbourg (September 1995) and

a meeting of the epidemiologists from the Pilot Projects (November 1995). Thanks are therefore due to

all those who participated in this review process and whose comments have influenced and helped

improve the document. The authors further wish to thank Anthony McDonnell for his assistance in

preparing the document.

II - A - 41


Glossary of terms

Additional imaging: after evaluation of the screening mammogram, additional imaging may be required for medical reasons. This may take the form of repeat mammography, specialised views (e.g. magnification, extended craniocaudal, paddle views), ultrasound or magnetic resonance imaging (MRI). Additional radiology includes additional views taken at the time of the screening mammogram, as well as those carried out on recall. It does not include repeat mammograms for technical reasons. It also does not include intermediate mammograms. On the basis of additional imaging, a woman may be dismissed, or may be recommended to have cytology or biopsy. Please note the difference between additional imaging and intermediate mammography.

Additional imaging rate: the number of women who have an additional imaging investigation as a proportion of all women who have a screening test. This includes additional images taken at the time of the screening test, as well as imaging for which women are recalled. The additional imaging rate does not include repeat mammography for technical reasons. It also does not include intermediate mammograms. Within the group with additional imaging, the rates of individual imaging procedures may be derived.

Adjuvant therapy: women with axillary lymph node metastases are assumed to receive adjuvant systemic therapy (chemotherapy and/or hormonal therapy).

Age-specific detection ratio: the number of breast cancers detected in a specified age category divided by the incidence of breast cancer in that same age category in the year before screening started.

Benign/malignant biopsy ratio: the ratio of pathologically-proven benign lesions to malignant lesions surgically removed in any round of screening. This ratio may vary between initial and subsequent screening examinations.

Breast cancer register: when a country or region does not have or can not access a pathology register and/or cancer register, a screening programme may take it upon itself to create a 'breast cancer register' specifically for the programme.

Cancer: a pathologically-proven malignant lesion which is classified as ductal carcinoma in situ or invasive breast cancer.

Cancer detection rate: the number of pathologically-proven malignant lesions (both in-situ and invasive) detected in a screening round per 1000 women screened in that round. This rate will differ for initial versus subsequent screening examinations. Cancers detected at intermediate mammography should be regarded as screen-detected cancers and thus be included in the cancer detection rate. Recurrent breast cancers, detected for the first time at mammographie screening, should also be regarded as screen-detected cancers since they will be identified and diagnosed in the same way as a primary breast cancer. Cancer metastases diagnosed in the breast as a consequence of a primary cancer outside the breast should not be included in the cancer detection rate.

Core biopsy: closed biopsy of a breast lesion providing a histological specimen of breast tissue for diagnostic purposes.

Cytology: techniques used to extract cells from breast lesions for cytological examination. Cytology can distinguish between cystic and solid breast lesions. Material from solid lesions can be examined cytologically for evidence of malignancy. Cytology may be performed with or without radiological (stereotactic) control. The latter may be referred to as Stereotactic Biopsy (STB) to distinguish it from

π - A - 42


cytology performed blindly, as in an outpatient clinic where a surgeon may aspirate a palpable breast lump for fluid or cells.

Dedicated screening unit: a unit that is used solely for screening examinations.

Dynamic cohort: a cohort, the composition of which is continuously changing allowing for the addition of new members for screening and follow up, and cessation of screening for those who become older than the maximum screening age. In order for estimates of screening efficacy to be accurately derived it is essential to know the denominator of the dynamic cohort at all times.

Eligible population: the adjusted target population, i.e. the target population minus those women that are to be excluded according to screening policy on the basis of criteria other than age, gender and geographic location.

Fixed cohort: a cohort into which there are no entries during the study period, including the follow up period. In a screening programme this means that a specific birth cohort is selected for screening and follow up. Women entering the age category in subsequent years of the screening programme are not included in the study cohort.

Further assessment: additional diagnostic techniques (either non-invasive or invasive) that are performed for medical reasons in order to clarify the nature of a perceived abnormality detected at the screening examination. Further assessment can take place at the time of the screening test or on recall.

Incidence rate (IR): the number of newly diagnosed cases of disease in a defined population within a defined time period.

Initial screening: first screening examination of individual women within the screening programme, regardless of the organisational screening round in which women are screened and regardless of previous invitations or reminders.

Intermediate mammography following screening: if, as a result of the screening test, a mammogram is required out of sequence with the screening interval (say at 3, 6 or 12 months), this is referred to as an intermediate mammogram following screening. Cancers detected at intermediate mammography should be regarded as screen-detected cancers (not interval cancers).

Intermediate mammography following further assessment: if, as a result of the screening test and further assessment, a mammogram is required out of sequence with the screening interval (say at 3, 6 or 12 months), this is referred to as an intermediate mammogram following further assessment. Cancers detected at intermediate mammography following further assessment should be regarded as screen-detected cancers (not interval cancers).

Interval cancer: a primary breast cancer which presents between two routine screening examinations, in a person dismissed as having had a negative screening test, or a 'negative for malignancy' outcome of further investigation of an abnormality detected at the screening examination.

Interval cancer rate: the number of interval cancers between two rounds of screening per 1000 women screened in the first of the two rounds.

Open biopsy: refers to surgical removal of a breast lesion.

II - A - 43


Open biopsy rate: the number of women undergoing open biopsy as a proportion of all women who have a screening examination. This rate may differ for initial versus subsequent screening examinations.

π - A - 44


Opportunistic screening: refers to screening which takes place outside an organised or population-based screening programme. This type of screening may be the result of e.g. a recommendation made during a routine medical consultation, consultation for an unrelated condition, on the basis of a possible increased risk of developing breast cancer (family history or other known risk factor).

Organisation register: registers of companies used to help identifying women from the target population for screening.

Participation rate: the number of women who have a screening test as a proportion of all women who are invited to attend for screening.

Primary treatment: all women with breast cancer, with or without signs of distant metastases, will receive a form of primary treatment, e.g. breast conserving surgery, mastectomy, chemotherapy, radiotherapy.

Population-based: a very specific epidemiological term which describes and emphasises the principle accurate denominator information. For a study to be population-based requires that relevant data be available for review on every member of the population under study. For a screening programme to be population-based every member of the target population who is eligible to attend on the basis of pre-decided criteria must be known to the programme.

Positive predictive value (PPV): refers to the ratio of lesions which are truly positive to those test positive. It is intimately effected by the prevalence of the condition under study. Thus, with a prevalence of < 1%, as with breast cancer, one can expect a low positive predictive and a very high negative predictive value for screening mammography.

PPV of additional imaging: the number of cancers detected as a proportion of the women with positive results in additional imaging (i.e. suspicion of malignancy). The denominator should include additional views performed for medical reasons at the time of the screening examination or on recall. Additional views taken for technical reasons should be excluded. Intermediate mammograms should also be excluded. In practice, the denominator corresponds to those women who, after additional imaging, undergo invasive tests for diagnostic confirmation.

PPV of cytology: the number of cancers detected as a proportion of the women with positive cytology (i.e. suspicion of malignancy). In practice, the denominator corresponds to those women who undergo biopsy after cytology.

PPV of recall: the number of cancers detected as a proportion of the women who were physically recalled for further assessment (but excluding those for technical recall).

PPV of recommendation for open biopsy: the number of cancers detected as a proportion of the women who were recommended for open biopsy. Since biopsy is the 'gold standard', i.e. the test used for diagnostic confirmation, there is no such thing as a PPV of open biopsy.

PPV of screening test: the number of cancers detected as a proportion of the women with a positive screening test. In practice, the denominator corresponds to women undergoing further assessment either at the time of screening or on recall. Further assessment does not include additional mammograms for technical reasons (repeat screening tests).

I I - A - 4 5


Recall: refers to women who are have to come back to the screening unit, i.e. who are physically recalled, as a consequence of the screening examination for: (a) a repeat mammogram because of a technical inadequacy of the screening mammogram (technical

recall); or (b) clarification of a perceived abnormality detected at the screening examination, by performance of an

additional procedure (recall for further assessment). This group is different from those who may have additional investigations performed at the time of the screening examination, but who were not physically recalled for that extra procedure.

Recall rate: the number of women recalled for further assessment as a proportion of all women who had a screening examination.

Recent mammogram: women who had a recent mammogram (either diagnostic or screening) may potentially be excluded from the target population and/or the results dependent on screening policy.

Repeat screening test: refers to the need to repeat a screening test for technical reasons, either at the time of the screening examination or on recall. The most common reasons for a repeat screening test are: a) processing error; b) inadequate positioning of the breast; or c) machine or operator errors. Technical recalls will be reduced considerably, though not necessarily completely eliminated, by on-site processing taking place before a woman is dismissed.

Screening interval: the fixed interval between routine screens decided upon in each screening programme dependent on screening policy.

Screening policy: the specific policy of a screening programme which dictates the targeted age and gender group, the geographic area to target, the screening interval (usually two or three years), etcetera.

Screening test: the test that is applied to all women in the programme. This may be a single or two- view mammogram with or without clinical examination. The screening test does not include additional imaging tests carried out at the time of the initial screening examination.

Screening unit: a screening unit refers to a building or facilities where screening examinations take place. It does not refer to the exact number of e.g. mammography machines within the unit.

Self-registration: women not invited for screening may present themselves and be included in the screening roster. It is the responsibility of the screening staff to decide whether self-registered women qualify to become members of the screening roster or not. It would be expected that only women who are members of the target population and thus eligible to attend would be allowed to self-refer.

Sensitivity: refers to the ratio of histologically-proven malignancies correctly identified at the screening examination to histologically-proven malignancies identified and not identified at the screening examination (i.e. true positives/true positives + false negatives). It is clear that to establish the sensitivity of the screening test in a particular programme there must be a flawless system for identification and classification of all interval cancers.

Sources of demographic data: demographic data for the purpose of issuing invitations to screening may come from a population register, an electoral register, other registers, population survey, or census data.

π - A - 46


Specificity: refers to the ratio of truly negative screening examinations to those that are truly negative and falsely positive (i.e. true negatives/true negatives + false positive). To derive an absolutely accurate estimate of specificity would require that each person dismissed as having a negative screening test is followed for ascertainment of subsequent negativity, and that those who are recalled for additional investigation following the screening test are regarded as potentially all having a malignancy. The false positives are those who have a histologically-proven benign lesion. A note of caution is warranted here, however, in that, not infrequently, it is known beforehand, on the basis of radiological investigation, that the offending lesion is benign. The reason for surgery on a benign lesion may be surgeon or patient preference for excision. In practice the ascertainment of specificity is frequently made on the basis of the results of initial mammograms.

Subsequent screening: all screening examinations of individual women within the screening programme following an initial screening examination, regardless of the organisational screening round in which women are screened.

Symptomatic women: women reporting breast complaints or symptoms at the screening examination may potentially be excluded from the target population and/or results according to screening policy.

Target population: all persons eligible to attend for screening on the basis of the following criteria: age, gender and geographic location (as dictated by the screening policy). This includes special groups such as institutionalised or minority groups.

Women invited: all women invited in the period to which data refer, even if they have yet to receive a reminder.

Women screened: all women screened in the period to which data refer, even if results of mammograms are not yet available.

World age-standardised rate: using 'direct' standardisation, this is the rate which would have occurred if the observed age-specific rates had operated in the standard world population:

I I - A - 4 7


Standard world population used for the computation of age-standardised mortality and incidence rates1:

Age (yrs) World

0 - 2 400 1 - 9 600 5- 10 000

10- 9 000 15- 9 000 20 - 8 000 25 - 8 000 30 - 6 000 35 - 6 000 40 - 6 000 45 - 6 000 50 - 5 000 55 - 4 000 60 - 4 000 65 - 3 000 70 - 2 000 75 - 1 000 80 - 500 85 + 500

total 100 000

Smith PG (1992) Comparison between registries: age-standardized rates. In: Parkin DM, Muir CS, Whelan SL, Gao Y-T, Ferlay J, Powell J (eds) Cancer Incidence in Five Continents, Volume VI. IARC Scientific Publications N-120, Lyon, ρ 865-870

Π - A - 48


II - Β CYTOPATHOLOGY GUIDELINES

produced by the

E.C. WORKING GROUP ON BREAST SCREENING PATHOLOGY

Editor:

Prof. J. Sloane

Content:

Il - Β CYTOPATHOLOGY GUIDELINES

Introduction II - Β - 1 Registering basic information II - Β - 2 Reporting categories II - Β - 3 Quality assurance II - Β - 5


Introduction

The term fine needle aspiration cytopathology (FNAC) is used throughout this document although it is recognised that a minority of units do not use suction for obtaining samples.

The success of FNAC is directly related to the skill and experience of the aspirator and there is strong evidence that the procedure is most successful when performed by a limited number of aspirators, who have been properly trained.

In most circumstances FNAC can be successfully carried out when:

1 easily palpable breast abnormalities are sampled freehand by a designated experienced clinician who may be a pathologist.

2 clinically equivocal and impalpable abnormalities are sampled under image guidance by a radiologist.

The number of aspirators in any one centre should be kept to a minimum and their performance audited.

Where resources allow it may be appropriate for the pathologist to perform aspiration him or herself. However, it would be unusual for the pathologist to have sufficient knowledge of mammography and ultrasound to undertake image-guided aspiration procedures independently of the radiologist although it is desirable for the pathologist to be present if resources allow. The pathologist is most likely to undertake aspiration where the breast assessment team has decided to provide a same-day cytology service or where there is a high percentage of inadequate specimens due to preparation problems or the lack of an experienced clinical aspirator. It is generally not appropriate for FNAC to be carried out in a separate clinic set up solely for this purpose. This is likely to be cost-effective only where the standard of aspiration would otherwise be poor and the pathologist has other symptomatic breast and non-breast referrals.

The decision about whether to operate on patients with screen-detected mammographie abnormalities involves the correlation of clinical, radiological and cytological findings (triple assessment). This is best achieved in multidisciplinary meetings where the clinician, radiologist and pathologist discuss these findings and reach a consensus on the management of each patient following pre-defined protocols.

I I - B - 1


Registering basic information

Information is registered using the standard registration form

Surname

Screening no

Slide

Specimen type

Localisation technique

Opinion

PATHOLOGIST

Registration Form

BREAST SCREENING CYTOPATHOLOGY

Forenames . . . .

Hospital no . . . .

D Right D Left

D FNA D FNA (solid lesion (cyst)

D Palpation D X-ray guided

G 1 Unsatisfactory

α 2 Benign

α 3 Atypia probably benign

α 4 Suspicious of malignancy

α 5 Malignant

Centre

α Nipple discharge

α Ultrasound guided

Comment

NAME OF ASPIRATOR

Date of birth

Report no

α Nipple or skin scrapings

DATE

Centre/location Give the name of the assessment centre, clinic, department etc., where the specimen was obtained.

Side Indicate right or left. For specimens from both sides, use a separate form for each slide.

Specimen type Please choose one of the following terms:

FNA (solid lesion) FNA (cyst)

Nipple discharge Nipple or skin

Fine needle aspiration of a solid lesion Fine needle aspiration of a cyst subjected to cytological examination Cytological preparation of a nipple discharge Cytological preparation of nipple or skin scrapings

Localisation technigue Please choose one of the following terms:

Palpation FNA guided by palpation Ultrasound guided FNA guided by ultrasound X-ray guided FNA guided by x-ray examination.

Stereotaxis is included in this category.

n - Β - 2


Pathologist

Aspirator

The name of the pathologist giving the cytological opinion.

The name of the person performing the fine needle aspiration.

Recording the cytology See the reporting categories below. A comment field is included for any extra opinion information to be recorded in free text.

Reporting categories

A definitive diagnosis of malignancy or benignity should be made wherever possible. The proportion of definitive diagnoses will clearly increase with the experience of both pathologist and aspirator.

C1 Inadequate

C2 Benign

Indicates a scanty or acellular specimen or poor preparation.

The designation of an aspirate as 'inadequate' is to a certain extent a subjective matter and may depend on the experience of the aspirator and/or the interpreter.

Poor cellularity (usually less than five clumps of epithelial cells) is sufficient to declare an aspirate inadequate. Preparative artefacts or excessive blood may also be reasons for rejecting an aspirate as inadequate.

Preparative artefacts include:

1. Crush, when too much pressure is used during smearing.

2. Drying, when dry smears are allowed to dry too slowly or when wet-fixed smears have been allowed to dry out before fixation.

3. Thick smears, when an overlay of blood, protein-rich fluid or cells obscurs the picture, making assessment impossible.

It is often helpful to make a comment as to the cause of the inadequate specimens in the Comment box on the form.

Indicates an adequate sample showing no evidence of malignancy.

The aspirate in this situation is often poorly to moderately cellular and tends to consist mainly of regular duct epithelial cells. These are generally arranged as monolayers and the cells have the characteristic benign cytological features. The background is usually composed of dispersed individual and paired naked nuclei. Should cystic structures be a component of the aspirated breast, then a mixture of foamy macrophages and regular apocrine cells may be part of the picture. Fragments of fibrofatty and/or fatty tissue are common findings.

A positive diagnosis of specific conditions, for example: fibroadenoma, fat necrosis, granulomatous mastitis, lymph node, etc., may be suggested if sufficient features are present to establish the diagnosis with confidence.

I I - B - 3


C3 Atypia probably benign

All the characteristics of a benign aspirate may be seen as described above. In addition, there are certain features not commonly seen in benign aspirates, including any of the following, alone or in combination: 1 nuclear pleomorphism 2 some loss of cellular cohesion 3 nuclear and cytoplasmic changes resulting from hormonal influence (pregnancy, contraceptive pill, HRT) or treatment effects. Increased cellularity may accompany the above features.

As thus defined, this group would be expected to contain approximately 20% of cases which were subsequently proven to be malignant.

C4 Suspicious of malignancy

The pathologist's opinion is that the material is suggestive but not diagnostic of malignancy. There are three main reasons: 1) the specimen is scanty, poorly preserved or poorly prepared, but

some cells with features of malignancy are present. 2) the sample may show some malignant features without overt

malignant cells present. The degree of abnormality should be more severe than in the previous category.

3) the sample has an overall benign pattern with large numbers of naked nuclei and/or cohesive sheets of cells, but with occasional cells showing distinct malignant features.

C5 Malignant

As thus defined, this group would be expected to contain approximately 80% of cases which were subsequently proven to be malignant.

Indicates an adequate sample containing cells characteristic of carcinoma, or other malignancy.

The interpreter should feel at ease in making such a diagnosis. Malignancy should not be diagnosed on the basis of a single criterion but on a combination of features.

Calcification It is very useful for the radiologist if the pathologist reports the presence of calcification within specimens taken from stereotactic or perforated plate guided FNAC when the abnormality is one of mammographie microcalcification. If calcification is present in these circumstances, the radiologist or multidisciplinary team can be more certain that the lesion has been sampled accurately and that the likelihood of a false negative due to an aspiration miss is lower. This may allow the team to advise with greater confidence that the woman be routinely recalled or rescreened early rather than subjected to biopsy. It is desirable to specify the type of calcification (hydroxyapatite or weddellite).

Calcification alone does not discriminate between benign and malignant conditions.

I I - Β - 4


Quality assurance

Definitions The following calculations are intended to reflect the quality of the FNAC service as a whole rather than the laboratory component alone. Inadequate FNAC results are not, therefore excluded from the calculations as in some publications. Cytologists wishing to evaluate purely their own accuracy in diagnosis may wish to calculate the figures differently.

Absolute sensitivity (C5) The number of carcinomas diagnosed as such (C5) expressed as a percentage of the total number of carcinomas aspirated.

Complete sensitivity (C3, 4 and 5)

= The number of carcinomas that were not definitely negative or inadequate on FNAC expressed as a percentage of the total number of carcinomas aspirated.

Specificity = The number of correctly identified benign lesions (the number of C2 results minus the number of false negatives) expressed as a percentage of the total number of benign lesions aspirated.

Positive predictive value = The number of correctly identified cancers of a C5 diagnosis (numbers of C5 results minus the number of

false positive results) expressed as a percentage of the total number of positive results (C5).

Positive predictive value = The number of cancers identified as suspicious of a C4 diagnosis (number of C4 results minus the number of false

suspicious results) expressed as a percentage of the total number of suspicious results (C4).

Positive predictive value = The number of cancers identified as atypia of a C3 diagnosis (number of C3 results minus the number of

benign atypical results) expressed as a percentage of the total number of atypical results (C3).

Negative predictive = The number of benign cases (including those value of a C2 diagnosis with no histology) expressed as a percentage

of the total number of C2 diagnoses.

False negative case A case which subsequently turns out (over the next 2 years) to be carcinoma having had a negative cytology result. (This will by necessity include some cases where the cancer was missed rather than misinterpreted in the smears. Furthermore, the interval may vary from one programme to another depending on the screening interval).

π - Β - 5


False positive case A case which was given a C5 cytology result but which turns out at open surgery to have a benign lesion (including atypical hyperplasia).

False negative rate The number of false negative results expressed as a percentage of the total number of carcinomas aspirated.

False positive rate The number of false positive results expressed as a percentage of the total number of carcinomas aspirated.

Inadequate rate The number of inadequate specimens expressed as a percentage of the total number of cases aspirated.

Suspicious rate The number of C3 and C4 diagnoses expressed as a percentage of the total number of cytology results.

How to calculate these figures

It is intended that a computer system will be able to calculate these figures automatically from the data in the database cross-referencing with the histology or subsequent outcome and a report derived for quality assurance purposes.

CYTOLOGY QA STANDARD REPORT Total cases screened in period Total assessed Total FNAC performed

Cytology

Histology

Total malignant

Invasive

Non-invasive

Total benign

No histology

Total C results

C5

Box 1

Box 7

Box 13

Box 19

Box 25

Box 31

C4

Box 2

Box 8

Box 14

Box 20

Box 26

Box 32

C3

Box 3

Box 9

Box 15

Box 21

Box 27

Box 33

C2

Box 4

Box 10

Box 16

Box 22

Box 28

Box 34

C1

Box 5

Box 11

Box 17

Box 23

Box 29

Box 35

Total

Box 6

Box 12

Box 18

Box 24

Box 30

Box 36

I I - B - 6


Each box (numbered 1 to 36) of the above table is calculated from the number of FNAC with a C code (C1, C2, etc.) cross-referenced with the worst histology diagnosis. The table and calculations (see below) should be produced for all FNAC tests (headed ALL TESTS) and also for all patients (headed ALL PATIENTS) where if two FNAC records are present the highest C number is taken. Only closed episodes should be used.

From the above table the sensitivity and specificity are then calculated in percentages for each of the categories in the cytology document. (The numbers correspond to BOX NUMBERS in the above table.)

1 ABSOLUTE SENSITIVITY = - 1 ^ x 100 6 + 25

(This assumes that all unbiopsied C5 results are carcinomas treated non surgically.)

2. COMPLETE SENSITIVITY = 1+2+3+25 x 100 6+25

3 SPECIFICITY 22

(biopsy cases only) = — * 100

22 28 4 SPECIFICITY (full) (This assumes that all cases of atypia (C3) which are not biopsied are benign.)

5 POSITIVE PREDICTIVE VALUE (C5 diagnosis)



8 NEGATIVE PREDICTIVE VALUE (C2)

9 FALSE NEGATIVE RATE (This EXCLUDES inadequate results)

24 27

=

,28+29

31-19 31

2 32-26

3 33

34-4 34

4

X

X

X

X

X

100

100

100

100

mn 6 + 25

10 FALSE POSITIVE RATE = —^- * 100 6 + 25

35 11 INADEQUATE RATE = — x 100

36

II - Β - 7


12 INADEQUATE RATE FROM CANCERS 6+25

x 100

13 SUSPICIOUS RATE 32 + 33

36 χ 100

It is recognized that the specificities are approximate and will be more accurate the longer the follow up.

Suggested minimum standards where therapy is partially based on FNAC

Absolute sensitivity (AS) Complete sensitivity (CS) Specificity (SPEC) (as calculated above) Positive predictive value (C5) (+PV) False negative rate (F-) False positive rate (F+) Inadequate rate (INAD) Inadequate rate in samples taken from carcinomas Suspicious rate

> 60% > 80% > 60%

(including non-biopsied cases) > 98%

<5% <1%

< 25% < 10% < 20%

These figures will obviously depend on aspiration techniques and the experience and care of the aspirator and will vary widely between units. The figures are interrelated and strategy to improve one figure will affect others. Thus attempts to reduce the inadequate rate will often increase the number of suspicious reports and attempts to improve the specificity will increase the false negative rate and so on. Also, reducing the benign biopsy rate by not sampling the majority of lesions with benign cytology will reduce the specificity where this is based on cases with benign histology rather than on the total.

A high proportion of impalpable cases aspirated in any series is likely to make the figures worse as there is more chance of missing a small area of microcalcification leading to a false negative or inadequate result and more likelihood of aspirating atypical hyperplasia, radial scars and tubular carcinomas, leading to a high level of suspicious or atypical reports. In screening with aspiration of impalpable lesions the results are likely to reveal lower values than those achieved in the symptomatic setting.

n - Β - 8


II - C QUALITY ASSURANCE GUIDELINES FOR PATHOLOGY IN MAMMOGRAPHY SCREENING

produced by the

E.C. WORKING GROUP ON BREAST SCREENING PATHOLOGY

Editor: Prof. J. Sloane

Content:

Il - C Quality Assurance Guidelines for Pathology in Mammography Screening

INTRODUCTION l l - C - 1

MACROSCOPIC EXAMINATION OF BIOPSY AND RESECTION SPECIMENS Biopsy Specimens Mastectomy Specimens

Axillary Dissection Specimens

USING THE HISTOPATHOLOGY REPORTING FORM Introduction Recording Basic Information Recording Benign Lesions

- C - 1 - C - 1 -C-2 -C-¿

- C - í - c - e -C-É - C - 7

TABLE 1. DISTINCTION OF PAPILLOMA FROM ENCYSTED PAPILLARY CARCINOMA I - C - £ Classifying Epithelial Proliferation

TABLE 2. COMPARISON OF HISTOLOGICAL FEATURES OF DUCTAL HYPERPLASIA AND DCIS

TABLE 3. DISTINCTION OF ATYPICAL LOBULAR HYPERPLASIA FROM LOBULAR C.I.S

CLASSIFYING MALIGNANT NON-INVASIVE LESIONS High Nuclear Grade DCIS Low Nuclear Grade DCIS Intermediate Nuclear Grade DCIS Mixed Types Other histological types

TABLE 4. DISTINCTION OF DUCTAL FROM LOBULAR CARCINOMA IN SITU Paget's disease Diagnosing Microinvasion Classifying Invasive Carcinoma Invasive cribriform carcinoma

RECORDING PROGNOSTIC DATA

REFERENCES

INDEX FOR SCREENING OFFICE PATHOLOGY SYSTEM

MEMBERSHIP OF WORKING GROUP

l - C - 1 2

I - C - 1 -

l - C - V

I - C - 1 Í I - C - 1 Í I - C - 1 Í I - C - 1 Í l - C - K l - C - K

l - C - 1 / I - C - 1 Ï i - c - 1 · I - C - 1 Í I - C - 1Í

I - C - 1 Í

I - C - 2'

I - C - 2(

l - C - 3

I I - C


INTRODUCTION

The success of a breast screening programme depends heavily on the quality of the pathological service. Specimens from screened women provide pathologists with particular problems of macroscopic and histological examination; the former principally result from identifying impalpable radiological abnormalities and the latter from classifying borderline lesions which are encountered with disproportionate frequency. Accurate pathological diagnoses and the provision of prognostically significant information are important to ensure that patients are managed appropriately and that the programme is properly monitored and evaluated. A standard set of data from each patient, using the same terminology and diagnostic criteria is essential to achieve the latter objective. The opinions expressed represent the consensus view of the EC. Working Group on Breast Screening Pathology and other pathologists who made written or verbal comments on this document and the United Kingdom document on which it is based. We hope that European pathologists involved in breast screening will find the guidance useful and the method of recording data convenient.

MACROSCOPIC EXAMINATION OF BIOPSY AND RESECTION SPECIMENS

Biopsy Specimens

Optimal handling

Palpable lesions

Confirming excision of radiological abnormality

Biopsies of mammographically detected lesions may provide especial difficulty in histological interpretation and consequently require optimal fixation and careful handling. Sometimes a photographic record of the sliced specimen, with the guide wire in position may be necessary to maximize the value of case discussions with clinical and radiological colleagues. Provision for macroscopic photography must, therefore, be borne in mind, especially for difficult cases. The surgeon should be discouraged from cutting the specimen before sending it to the pathologist and should ideally mark it with sutures in order to obtain proper orientation. Sutures are preferable to metal staples which often retract into the specimen, thus becoming impossible to recognize, and may obscure microcalcifications. A code of orientation for the sutures needs to be established and indicated on the request form. Palpable lesions detected in the screening programme may be dealt with by conventional methods and there is no especial virtue in specimen radiography, assuming that there is no doubt that the radiological and palpable lesions are one and the same. After excision, the intact specimen - with guide wire in situ - must be x-rayed. Ideally this procedure is carried out by the staff of the radiological department, so that the radiologist or surgeon can determine whether the relevant lesion has been resected. It may be necessary on medico-legal grounds for centres to name consultants responsible for confirming that mammographie lesions have been removed. Ideally those consultants should be the radiologists who interpreted the clinical mammograms. A good working relationship between pathologists, surgeons and radiologists is essential. Two copies of the specimen radiograph at this time could be taken with benefit, one for the department of radiology and one for the pathologist.

II - c - 1


If mammographie abnormality not identified

Fresh specimens

Frozen sections

Fixation

Excision margins

Naked eye examination

Specimen radiography

Clearly there will be a few occasions when the mammographie abnormality cannot be identified in the specimen. This may result from the excision of a lesion producing only architectural change in the clinical mammogram or from unsuccessful surgical localization. Detailed pathological examination should still be undertaken even in the latter case and the findings communicated to the surgeon. Clinical mammography can subsequently be repeated to determine if the lesion is still present in the breast. Specimens should be examined within 2-3 hours if received fresh. Samples for oestrogen receptor determination should be snap frozen in liquid nitrogen within 30 minutes of excision if a ligand binding assay is used. It should be remembered, however, that oestrogen receptor status can adequately be determined on standard formalin-fixed, paraffin-embedded sections.1,2

Rapid frozen sectioning is generally inappropriate in the assessment of clinically impalpable lesions. Rarely, however, it may be justified to enable a firm diagnosis of invasive carcinoma to be made in order to allow definitive surgery to be carried out in one operation. Three essential criteria, however, must be fulfilled: 1) the mammographie abnormality must be clearly and unequivocally identified on macroscopic examination 2) it must be large enough (generally at least 10mm) to allow an adequate proportion of the lesion to be fixed and processed without prior freezing 3) it must have proved impossible to make a definitive diagnosis preoperative^. The intact specimen may be examined in the fresh state or after fixation. Good fixation is very important to preserve the degree of morphological detail needed to diagnose borderline lesions and report features of prognostic significance, particularly grade and vascular invasion. Small specimens may be fixed whole but larger ones should be examined and sliced within 2-3 hours of excision, if possible, to allow adequate penetration of fixative. In order to demonstrate adequacy of excision, the entire surface of the specimen should be painted with India ink, radiolucent pigments, dyed gelatin or other suitable material. An appropriate period of drying must be allowed if spread of the chosen reagent is to be avoided. After determining its weight (and size if required), the specimen is then serially sliced at intervals of up to 4mm. The cut surfaces are examined by careful visual inspection. Palpation may also be informative. The maximum diameter, contour, colour and consistency of any macroscopic lesion are recorded. The size of lesions measured macroscopically should be checked later on histological sections as the true extent of the abnormality is not always appreciated by macroscopic inspection alone. If different, the histological dimensions should be accepted as the true size. In the case of malignant lesions, adequacy of excision should be assessed by naked eye and later by microscopic examination. Unless a lesion obviously accounting for the radiological abnormality is identified, a second radiograph of the sliced specimen should be performed. It is desirable for the pathologist to give a brief description of the abnormality in the specimen radiograph during macroscopic examination. Blocks should then be taken from the areas corresponding to the mammographie abnormalities and any other macroscopically suspicious zones. This method allows precise correlations to be made between the radiological and histological appearances and may serve as a reference map for orientation

π - c - 2


Histological characterization of mammographie changes

Choice of specimen mammography equipment

Extent of sampling

Large blocks

and reconstruction purposes. It is thus the favoured method of specimen radiography. It has been found, however, to be too time-consuming for some laboratories to undertake. A number of shorter, one stage, methods have been reported. For reviews see Anderson and Armstrong & Davies.34

Whichever method is adopted, pathologists must satisfy themselves that the pathological changes responsible for mammographie abnormalities have been identified in the histological sections; it may be necessary to consult with radiologists to be certain of this. If not, the residual unblocked tissue and/or blocks should be re-x-rayed. Any residual tissue should be stored until the mammographie changes have been characterized histologically. It is not recommended that tissue is simply taken from around a guide wire introduced pre-operatively which may not necessarily be very close to the mammographie abnormality. Although it is possible to prepare adequate mammographs of specimens using a clinical mammography machine, this approach may present logistical difficulties. There are several dedicated specimen mammography cabinets on the market. Their characteristics, mode of operation and the use of accessories have been described in a recent publication by the English Department of Health.5

The precise number of blocks to be taken cannot be stated dogmatically and clearly depends on the size and number of lesions present. With small biopsies, all the tissue should be blocked and examined. For malignant tumours in excess of 20mm, about 3 blocks of the tumour are desirable. Where possible, at least one block should include the edge of the tumour and the nearest excision margin to enable measurement of this distance, in mm., on the histological sections. For larger biopsies which cannot be blocked in toto, some sampling of radiologically and macroscopically normal breast should be undertaken in order to increase the detection of small occult cancers (particularly in situ change) and atypical proliferative lesions. The frequency with which such lesions are detected incidentally in unscreened women depends on the number of blocks taken.6 The extent of sampling of biopsies containing benign screen-detected mammographie abnormalities should be decided locally and will depend, amongst other things, on the extent of local resources. Additional sampling is more effective if restricted to fibrous parenchyma, ignoring the adipose tissue. Large blocks and sections are used in some laboratories where they are found to be of value in identifying screen-detected lesions as well as in determining their size, extent of spread and adequacy of excision. They facilitate orientation by obviating the need for mental reconstruction of the overall picture from several separate sections. They also reduce the number of blocks required.7 Other workers, however, have encountered problems in achieving adequate fixation and good cytological detail in addition to the technical difficulties of cutting large sections and the problems in storing them. These drawbacks can be overcome, but large blocks, although of value, are not regarded as essential for examining specimens from screened women and their use should depend on local preference.

Naked eye examination Mastectomy Specimens Mastectomy specimens should be dealt with within 2 hours of removal and either examined in the fresh state or incised before fixation to allow adequate

l i - c - 3


penetration of fixative. The favoured method of examination is by slicing the breast from the deep surface in the sagittal plane after measuring the dimensions or recording the weight. The slices should be about 10mm thick and may be left joined by the skin or separated completely and arranged in order. The maximum diameter of the main lesion should be measured and the distance from the nearest margin of excision determined as for biopsies (see earlier).

Sampling Blocks of tumour (the number depending on tumour size as above) should be taken to include the edges and should always be sufficient to represent the maximum extent of the lesion noted macroscopically. Blocks of the nearest excision margin should be taken. Painting with India ink or pigments may be helpful as in local excision specimens. If the tumour has been removed, then 3-4 blocks should be taken from the cavity wall. The breast slices should be examined by careful naked eye inspection and palpation. Blocks should be taken from any suspicious areas, noting the quadrant in which they are located. At least one block should be taken from each quadrant and ideally two from the nipple - one in the sagittal and one in the coronal plane through the junction with the areola. Axillary Dissection Specimens Axillary contents received with mastectomy or biopsy specimens should be examined carefully to maximize lymph node yield. This is usually achieved by cutting the specimen into thin slices which are then examined by careful inspection and palpation. The use of clearing agents or Bouin's solution may increase lymph node yield but are time-consuming and expensive of reagents and not regarded as essential. The axillary contents can be divided into three levels if the surgeon has marked the specimen appropriately.

Sampling Pathological examination should be performed on all lymph nodes received and the report should state the total number and the number containing metastases. A representative complete section of any grossly involved lymph node is adequate. For nodes greater than 5mm in maximum dimension, three slices should be taken and processed in a single block. Nodes less than 5mm should be embedded in their entirety. They can be processed in groups and are ideally examined at two levels.

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EUROPEAN BREAST SCREENING

HISTOPATHOLOGY

Surname Forenames Date of birth

Screening no Hospital No Side: D RIGHT o LEFT

PATHOLOGIST Date of reporting Report No

Histological calcification D Absent D Benign D Malignant α Both

Specimen radiograph seen? D YesD No Mammographie abnormality present in specimen D Yes G No α Both

Specimen type D Localisation biopsy D Open biopsy D Segmental excision G Mastectomy α Wide bore needle core

Specimen Weight g Size mm χ mm χ mm

BENIGN LESION PRESENT

G Complex sclerosing lesion/radial scar G Periductal mastitis/duct ectasia α Fibroadenoma D Fibrocystic change α Other (please specify)

EPITHELIAL PROLIFERATION

α Not present

α Present without atypia

MALIGNANT LESIONS NON-INVASIVE

G Not present G Ductal, high grade

Growth pattern(s) .

D Lobular

MICROINVASION

INVASIVE

G Paget's

D Not present

α Not present α Ductal / no specific type (NST) α Lobular carcinoma α Medullary carcinoma

D Other primary carcinoma (please specify) α Other malignant tumour (please specify) .

α Multiple papilloma α Solitary papilloma G Sclerosing adenosis α Solitary cyst

α Present with atypia (ductal) α Present with atypia (lobular)

α Ductal, other Cell type/pattern

SIZE (Ductal only)

α Present α Possible

α Mucinous carcinoma D Tubular carcinoma D Mixed (please tick component types present) D Not assessable

MAXIMUM DIAMETER OF INVASIVE TUMOUR WHOLE SIZE OF TUMOUR (to include DCIS extending >1 mm

mm beyond invasive area)

AXILLARY NODES PRESENT OTHER NODES PRESENT

EXCISION MARGINS

GRADE

DISEASE EXTENT

D Yes α No α Yes D No

Site of other nodes

D Reaches margin

Dl

D Localised

Number positive Total number Number positive Total number

VASCULAR INVASION (blood or lymphatic)

COMMENTS/ADDITIONAL INFORMATION

α Uncertain D Does not reach margin (nearest. . . .mm)

a l l Gill G Not assessable

D Multiple α Not assessable

α Present α Not seen

HISTOLOGICAL DIAGNOSIS D NORMAL G BENIGN G MALIGNANT

II - C - 5


USING THE HISTOPATHOLOGY REPORTING FORM

Introduction This section gives guidance on how to use the histopathology form and provides definitions of the terms used. The aim is not to replace standard texts on breast histopathology but to focus on diagnostic criteria for including lesions in the various categories and therefore help to achieve maximum uniformity of reporting. The guidance in this section is drawn from standard textbooks of breast pathology and other published data. Reporting forms can be obtained from, or may be computer-generated in, screening offices. It is not necessary to use the form as it appears in this document. It may be found desirable to undertake modifications locally, particularly if the form is also to function as the definitive pathology report to be entered in patients' notes and laboratory records. It is, of course, essential to record all the information requested by the form for submission to screening offices using exactly the same terminology. Evaluation of breast screening programmes depends upon provision of accurate pathology data.

Side:

Pathologist: Date: Histological calcification: Specimen radiograph seen? Mammographie abnormality present in specimen?

Specimen type

Specimen weight

Recording Basic Information Indicate left or right. For specimens from both sides, use one form for each side. The pathologist should enter their name. Enter the date the specimen was reported. Indicate if calcification observed radiologically is seen in histological sections and, if so, whether it is present in benign or malignant changes or both. Please indicate if you have seen a specimen radiograph.

Are you satisfied that the mammographie abnormality is present in the specimen? This may necessitate consultation with the radiologist responsible for examining the specimen radiograph. It is worth remembering that breast calcification is occasionally due to oxalate salts (Weddelite) which can only be detected satisfactorily in histological sections using polarized light.8

Please choose one of the following terms: - Localization biopsy Biopsy of impalpable lesion identified by

radiologically guided marking. Non-guided biopsy/excision, lumpectomy, tylectomy, dochectomy. Include: wedge excisions, partial mastectomies and re-excision specimens for clearance of margins. Where specimen includes all or nearly all of the breast parenchymal tissue. Include: subcutaneous mastectomy, total glandular mastectomy, simple mastectomy, extended simple mastectomy, modified radical mastectomy, radical mastectomy, Patey mastectomy, supra-radical mastectomy. Pre-operative diagnostic needle biopsy, e.g. trucut, screw, etc.

Please record the weight and/or size of all biopsy and segmental excision specimens. Weight is a more reproducible method of estimating the size of a specimen than 3 dimensional measurements to determine volume, even

Open biopsy

Segmental excision

Mastectomy

- Wide bore needle core

I I - C - 6


taking into account the different densities of fat and fibrous tissue, which form varying proportions of breast specimens

Fibroadenoma

Papilloma

Recording Benign Lesions A benign malformation composed of connective tissue and epithelium exhibiting a pericanalicular and/or intracanalicular growth pattern. The connective tissue is generally composed of spindle cells but may rarely also contain other mesenchymal elements such as fat, smooth muscle, osteoid or bone. The epithelium is usually double-layered but some multilayering is not uncommon. Changes identical to those found in lobular epithelium elsewhere in the breast (e.g. apocrine metaplasia, sclerosing adenosis, blunt duct adenosis, hyperplasia of usual type, etc.) may occur in fibroadenomas but need not be recorded separately unless they amount to atypical hyperplasia or in situ carcinoma. Sometimes individual lobules may exhibit increased stroma producing a fibroadenomatous appearance and occasionally such lobules may be loosely coalescent. These changes are often called fibroadenomatoid hyperplasia or sclerosing lobular hyperplasia but may be recorded as fibroadenoma on the reporting form if they produce a macroscopically visible or palpable mass. Consequently, fibroadenomas need not be perfectly circumscribed. Old lesions may show hyalinization and calcification (and less frequently ossification) of stroma and atrophy of epithelium. Fibroadenomas are occasionally multiple. For the purposes of the screening form, tubular adenomas can be grouped under fibroadenomas. Fibroadenomas should be distinguished from phyllodes tumours. The high grade or 'malignant' phyllodes tumours are easily identified by their sarcomatous stroma. The low grade variants are more difficult to distinguish but the main feature is the more cellular stroma. Phyllodes tumours may also exhibit an enhanced intracanalicular growth pattern with club-like projections into cystic spaces and there is often overgrowth of stroma at the expense of the epithelium. Adequate sampling is important as the characteristic stromal features may be seen only in parts of the lesion. Although phyllodes tumours are generally larger than fibroadenomas, size is not an acceptable criterion for diagnosis; fibroadenomas may be very large and phyllodes tumours small. For purposes of convenience, low grade phyllodes tumours should be specified under 'other benign lesions' and high grade under 'other malignant tumour' although it is recognized that histological appearance is often not a good predictor of behaviour. A papilloma is defined as a tumour with an arborescent, fibrovascular stroma covered by epithelium generally arranged in an inner myoepithelial and outer epithelial layer. Epithelial hyperplasia without cytological atypia is often present and should not be recorded separately. Atypical hyperplasia is rarely seen and, when present, should be recorded separately under 'Epithelial Proliferation'. Epithelial nuclei are usually vesicular with delicate nuclear membranes and inconspicuous nucleoli. Apocrine metaplasia is frequently observed but should not be recorded separately on the reporting form. Squamous metaplasia is sometimes seen, particularly near areas of infarction. Sclerosis and haemorrhage are not uncommon and where the former involves the periphery of the lesion, may give rise to epithelial entrapment with the false impression of invasion. The benign cytological features of such areas

I I - C - 7


should enable the correct diagnosis to be made. The term 'intracystic papilloma' is sometimes used to describe a papilloma in a widely dilated duct. These tumours should simply be classified as papilloma on the form. (For distinction from encysted papillary carcinoma, Table 1.) Papillomas may be solitary or multiple. The former usually occur centrally in sub-areolar ducts whereas the latter are more likely to be peripheral and involve terminal duct lobular units. The distinction is important as the multiple form is more frequently associated with atypical hyperplasia and ductal carcinoma in situ, the latter usually of low grade type which should be recorded separately. This malignant change may be restricted to small foci and extensive sampling may be required to detect it. Some sub-areolar papillomas causing nipple discharge may be very small and extensive sampling may be required to detect them. Lesions termed ductal adenoma exhibit a variable appearance which overlaps with other benign breast lesions. They may resemble papillomas except that they exhibit an adenomatous rather than a papillary growth pattern. These cases should be grouped under papilloma on the form. Indeed, some tumours may exhibit papillary and adenomatous features. Some ductal adenomas may show pronounced central and/or peripheral fibrosis and overlap with complex sclerosing lesions (see ρ 10). The condition of adenoma of the nipple (sub-areolar duct papillomatosis) should not be classified as papilloma in the screening form but specified under 'Benign Lesions, Other'. Diffuse microscopic papillary hyperplasia should be recorded under 'Epithelial Proliferation' in the appropriate box depending on whether atypia is present or not.

II - c


TABLE 1. DISTINCTION OF PAPILLOMA FROM ENCYSTED PAPILLARY CARCINOMA Histological features Papilloma encysted papillary carcinoma

1) Fibrovascular cores

2) Cells covering papillae

a) basal

b) luminal

3) Mitoses

4) Apocrine metaplasia

5) Surrounding tissue

6) Necrosis and haemorrhage

7) Periductal and intratumoural fibrosis

Usually broad and extend throughout the lesion

Myoepithelial layer always present

Single layer of regular luminal epithelium OR features of regular usual type hyperplasia

Infrequent with no abnormal forms

Common

Benign changes may be present including regular epithelial hyperplasia

May occur in either. Not a useful discriminating feature.

May occur in either. Not a useful discriminating feature.

Very variable, usually fine and ma be lacking in at least part of the lesion

Myoepithelial cells usually absent but may form a discontinuous lay«

Cells often taller and more monotonous with oval nuclei, the long axes of which lie perpendicul to stromal core of papillae. Nude may be hyper-chromatic. Epitheli multi-layering frequent, often producing cribriform and micropapillary patterns of DCIS overlying the papillae or lining the cyst wall.

More frequent; abnormal forms m be seen

Rare

Surrounding ducts may show due carcinoma in situ

NB: All the features of a lesion should be taken into account when making a diagnosis. No criterion is reliable alon

Sclerosing adenosis Sclerosing adenosis is an organoid lobular enlargement in which increased numbers of acinar structures exhibit elongation and distortion. The normal two cell lining is retained but there is myoepithelial and stromal hyperplasia. The acinar structures may infiltrate adjacent connective tissue and occasionally nerves and blood vessels, which can lead to an erroneous diagnosis of malignancy. Early lesions of sclerosing adenosis are more cellular and later ones more sclerotic. Calcification may be present. There may be coalescence of adjacent lobules of sclerosing adenosis to

n - c - 9


form a mass detectable by mammography or macroscopic examination. The term 'adenosis tumour' has been used to describe such lesions.9 It is recommended that sclerosing adenosis is not entered on the screening form if it is a minor change detectable only on histological examination. Although sclerosing adenosis often accompanies fibrocystic change (see below), this is not always the case and the two changes should be recorded separately. Occasionally apocrine metaplasia is seen in areas of sclerosing adenosis (apocrine adenosis). It can produce a worrying appearance and should not be mistaken for malignancy.10

Rarely, the epithelium in sclerosing adenosis may show atypical hyperplasia or in situ carcinoma. In such cases, please record these changes separately on the reporting form. The differential diagnosis of sclerosing adenosis includes tubular carcinoma, microglandular adenosis and radial scar. In tubular carcinoma, the infiltrating tubules lack basement membrane, myoepithelium, a lobular organoid growth pattern and exhibit cytological atypia. Ductal carcinoma in situ is a frequent accompaniment. Microglandular adenosis differs from sclerosing adenosis in lacking the lobular organoid growth pattern and being composed of rounded tubules lined by a single layer of cells lacking cytological atypia. The glandular distortion of sclerosing adenosis is lacking. Radial scar is distinguished from sclerosing adenosis by its characteristic floret-type growth pattern with ducto-lobular structures radiating out from a central zone of dense fibro-elastotic tissue. Furthermore, the compression of tubular structures associated with myoepithelial and stromal hyperplasia is lacking.

Complex sclerosing Under this heading are included sclerosing lesions with a pseudoinfiltrative lesion/radial scar growth pattern which have been called various names including infiltrating

epitheliosis, rosette-like lesions, sclerosing papillary proliferation, complex compound heteromorphic lesions, benign sclerosing ductal proliferation, non-encapsulated sclerosing lesion, indurative mastopathy and proliferation centre of Aschoff. The radial scar is generally 10mm or less in diameter and consists of a central fibro-elastotic zone from which radiate out tubular structures which may be two-layered or exhibit intra-luminal proliferation. Tubules entrapped within the central zone of fibro-elastosis exhibit a more random, nonorganoid arrangement. Lesions greater than 10mm are generally termed complex sclerosing lesions. They have all the features of radial scars and, in addition to their greater size, exhibit more disturbance of structure, often with nodular masses around the periphery. Changes such as papilloma formation, apocrine metaplasia and sclerosing adenosis may be superimposed on the main lesion. Some complex sclerosing lesions give the impression of being formed by coalescence of several adjacent sclerosing lesions. There is a degree of morphological overlap with some forms of ductal adenoma. If the intra-luminal proliferation exhibits atypia or amounts to in situ carcinoma, it should be recorded separately under the appropriate heading on the screening form. The main differential diagnosis is carcinoma of tubular or low grade 'ductal' type. The major distinguishing features are the presence of myoepithelium and basement membrane around the tubules of the sclerosing lesions. Cytological atypia is also lacking and any intra-tubular proliferation

II - C - 10


Fibrocystic change

Solitary cyst

Periductal mastitis/ectasia (plasma cell mastitis)

Other (specify)

resembles hyperplasia of usual type unless atypical hyperplasia and/or in situ carcinoma are superimposed (see above). Tubular carcinomas generally lack the characteristic architecture of sclerosing lesions. This term is used for cases with several to numerous macroscopically visible cysts, the majority of which are usually lined by apocrine epithelium. The term is not intended for use with minimal alterations such as fibrosis, microscopic dilatation of acini or ducts, lobular involution, adenosis and minor degrees of blunt duct adenosis. These changes should be indexed as normal. It is not intended that cystic change or apocrine metaplasia occurring within other lesions such as fibroadenomata, papillomata or sclerosing lesions should be coded here. Apocrine metaplasia occurring in lobules without cystic change may produce a worrisome appearance, occasionally mistaken for carcinoma. This change should be specified as 'apocrine adenosis' under other benign lesions. Papillary apocrine hyperplasia should be indexed separately under epithelial proliferation with or without atypia, depending on its appearance. It should be noted, however, that apocrine cells usually exhibit a greater degree of pleomorphism than is seen in normal breast cells. Hyperplasia should therefore be regarded as atypical only when the cytological changes are significantly more pronounced than usual. This term should be used when the abnormality appears to be a solitary cyst. The size is usually greater than 10mm and the lining attenuated or apocrine in type. The latter may show papillary change which should be indexed separately under epithelial proliferation of appropriate type. If multiple cysts are present, it is better to use the term 'fibrocystic change' as above. Intra-cystic papillomas and intra-cystic papillary carcinomas should not be entered here but under papilloma or carcinoma. This process involves larger and intermediate size ducts, generally in subduct areolar location. The ducts are lined by normal or attenuated epithelium, filled with amorphous, eosinophilic material and/or foam cells and exhibit marked periductal chronic inflammation, often with large numbers of plasma cells. There may be pronounced periductal fibrosis. The inflammatory infiltrate may contain large numbers of histiocytes giving a granulomatous appearance. Calcification may be present. The process may ultimately lead to obliteration of ducts leaving dense fibrous masses. Persistence of small tubules of epithelium around the periphery of an obliterated duct result in a characteristic garland pattern. Duct ectasia is often associated with nipple discharge or retraction. Cysts are distinguished from duct ectasia by their rounded rather than elongated shape, tendency to cluster, lack of stromal elastin, frequent presence of apocrine metaplasia and less frequent presence of eosinophilic material or foam cells in the lumina.

Mammary duct fistula (recurring sub-areolar abscess) should be coded under'Benign, Other'. This category is intended for use with less common conditions which form acceptable entities but cannot be entered into the categories above, e.g. fat necrosis, lipoma, adenoma of nipple, low grade phyllodes tumours. The index at the end of the booklet should help as a reference for lesions difficult to place in any of the above categories.

π - c -11


Not present

Present without atypia

Present with atypia (ductal)

Classifying Epithelial Proliferation This section is for recording intra-luminal epithelial proliferation in terminal duct lobular units or ¡nter-lobular ducts. This should be ticked if there is no epithelial multilayering (apart from that ascribed to cross-cutting) or if there is slight multilayering without atypia, not exceeding 4 cells in thickness. This term is used to describe all cases of intra-luminal proliferation showing no or only minor atypia where the epithelial cells are more than 4 thick. The change may involve terminal duct lobular units or inter-lobular ducts. The major features which distinguish hyperplasia from ductal carcinoma in situ of low nuclear grade are summarized in Table 2. Hyperplasia of usual type should be recorded if it occurs alone or in association with cystic change or other benign lesions, but not if it is confined to fibroadenomas, adenomas, papillomas or radial scars/complex sclerosing lesions. The term should be used for cases where there is no atypia or atypia of only minor degree, insufficient to raise the possibility of DCIS. If a diagnosis of atypical ductal hyperplasia (ADH) is contemplated, then extensive sampling should be undertaken to search for evidence of unequivocal DCIS with which it frequently co-exists. ADH is a rare lesion often co-existing with fibrocystic change, a sclerosing lesion or a papilloma. Its current definition rests on identification of some but not all features of ductal carcinoma in situ. Most of the difficulties are encountered in distinguishing ADH from the low grade variants of DCIS. The main features of low grade DCIS are I a uniform population of cells II even cellular placements III smooth geometric spaces between 'rigid' bars or micropapillary

formations IV hyperchromatic nuclei ADH has some but not all of the features described above. A diagnosis of DCIS should be reserved for lesions having all these features present in at least two or more duct spaces. Table 2 provides more details of features which serve to distinguish ADH from usual type hyperplasia and ductal carcinoma in situ. Useful rules of thumb to distinguish atypical ductal hyperplasia from ductal carcinoma in situ are: 1) restrict the diagnosis of ADH to cases where the diagnosis of DCIS

is seriously considered but in which the features are not sufficiently developed for a confident diagnosis.

2) DCIS usually extends to involve multiple duct spaces and is rarely under 2-3mm in extent. In any lesion where the process with the above features extends widely, a diagnosis of atypical ductal hyperplasia should be questioned.

For further guidance, the reader is referred to Page & Rogers.11

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TABLE 2. COMPARISON OF HISTOLOGICAL FEATURES OF DUCTAL HYPERPLASIA AND DCIS*

Histological features

Size

Cellular composition

Architecture

Lumina

Cell orientation

Nuclear spacing

Epithelial/tumour cell character

Nucleoli

Mitoses

Necrosis

Usual type ductal hyperplasia

Variable size but rarely extensive unless associated with other benign processes such as papilloma or radial scar

Mixed. Epithelial cells and spindle-shaped cells** present. Lymphocytes and macrophages may also be present. Myoepithelial hyperplasia may occur around the periphery

Variable

Irregular, often ill-defined peripheral slit-like spaces are common and a useful distinguishing feature

Often streaming pattern with long axes of nuclei arranged parallel to direction of cellular bridges which often have a tapering' appearance

Uneven

Small ovoid but showing variation in shape

Indistinct

Infrequent with no abnormal forms

Rare

Atypical ductal hyperplasia

Usually small (less than 2-3mm) unless associated with other benign processes such as papilloma or radial scar

May be uniform single population but merges with areas of usual type hyperplasia within the same duct space. Spindle-shaped cells may be intermingled with the proliferating cells

Micropapillary, cribriform or solid patterns but may be rudimentary

May be distinct, well formed rounded spaces in cribriform type. Irregular, ill-defined lumina may also be present

Cell nuclei may be at right angles to bridges in cribriform types, forming 'rigid' structures

May be even or uneven

Small uniform or medium sized monotonous cell populations present at least focally

Single small

Infrequent, abnormal forms rare

Rare

Low nuclear grade DCIS

Rarely less than 2-3mm an may be very extensive

Single cell population. Spindle-shaped cells not seen. Myoepithelial cells usually in normal location around duct periphery but may be attenuated

Well developed micropapillary cribriform orso patterns

Well delineated, regular punched out lumina in cribriform type

Micropapillary structures with indiscernible fibrovascular cores or smootl well-delineated geometri spaces. Cell bridges 'rigi in cribriform type with nuclei orientated toward; the luminal space

Even

Small uniform monotonous cell population

Single small

Infrequent, abnormal form: rare

If present, confined to sma particulate debris in cribriform and/or luminal spaces

Major diagnostic features are shown in bold type.

* See Page & Rogers11

**These cells are usually called myoepithelial cells but immunohistological studies have shown that they have characte of basal keratin type epithelial cells12

II - C - 1 3


Present with atypia (lobular)

This change is characterized by proliferation within terminal duct lobular units of characteristic small rounded cells similar to those seen in lobular carcinoma in situ. The major points of distinction from the latter are summarized in Table 3. Like the ductal variety, atypical lobular hyperplasia occurs in about 2% of non-cancer containing biopsies from unscreened women.

TABLE 3. DISTINCTION OF ATYPICAL LOBULAR HYPERPLASIA FROM LOBULAR CARCINOMA IN SITU


Cellular composition

Cell cohesion

Cell spacing

Luminal occlusion

Lobular distension

Pagetoid spread into interlobular ducts

Atypical lobular hyperplasia

Polymorphic. Cells similar to those seen in LCIS accompanied by spindle-shaped cells, leucocytes and other epithelial cells

Usually good

Irregular

Partial

Slight

Very uncommon

Lobular carcinoma in situ

Monomorphic proliferation of chracteristic small rounded cells with granular or hyperchromatic nuclei, inconspicuous nucleoli and high nucleo-cytoplasmic ratio

Often poor

Regular

Complete

Moderate to marked

Common

NB: All the features of a lesion should be taken into account when making a diagnosis. No criterion is reliable alone.

II - C - 14


Classifying Malignant Non-Invasive Lesions

Ductal carcinoma Ductal carcinoma in situ (DCIS) is defined as a proliferation of epithelial in situ cells with cytological features of malignancy within parenchymal structures

of the breast and is distinguished from invasive carcinoma by the absence of stromal invasion across the basement membrane. DCIS varies in cell type, growth pattern and extent of disease and may thus represent a group or spectrum of related in situ neoplastic processes. Classification has traditionally been according to growth pattern but has been carried out with little enthusiasm given a perceived lack of clinical relevance. More recently, evidence has emerged that lesions composed of cells of high nuclear grade are more aggressive.13,14 There is currently no generally accepted method of classifying DCIS but distinction between common histological subtypes is of value for correlating pathological and radiological appearances, improving diagnostic consistency, assessing the likelihood of invasion and determining the probability of recurrence after local excision. Despite the name, most DCIS is generally considered to arise from the terminal duct lobular units. The main points of distinction from lobular carcinoma in situ are summarized in Table 4. For measurement of size see p. 19. The nuclear grading system adopted below is derived from that employed by Hollandetal.15.

High Nuclear Grade DCIS This is composed of cells with pleomorphic, irregularly-spaced and usually large nuclei exhibiting marked variation in size, irregular nuclear contours, coarse chromatin and prominent nucleoli. Mitoses are frequently present and abnormal forms may be seen. High nuclear grade DCIS may exhibit several different growth patterns. It is often solid with central, comedo-type necrosis which frequently contains deposits of amorphous calcification. This is the easiest pattern to recognize. Sometimes a solid proliferation of malignant cells fills the duct without necrosis but this is relatively rare and is usually confined to nipple ducts in cases presenting with Paget's disease. High nuclear grade DCIS may also exhibit micropapillary and cribriform patterns frequently associated with central, comedo-like necrosis. Unlike low nuclear grade DCIS, there is rarely any polarization of cells covering the micropapillae or lining the intercellular spaces.

Low Nuclear Grade DCIS This is composed of monomorphic, evenly-spaced cells with roughly spherical, centrally-placed nuclei and inconspicuous nucleoli. The nuclei are usually, but not invariably, small. Mitoses are few and there is rarely individual cell necrosis. The cells are generally arranged in micropapillary and cribriform patterns which are frequently present within the same lesion, although the latter is more common and tends to predominate. There is usually polarization of cells covering the micropapillae or lining the intercellular lumina. Less frequently, low nuclear grade DCIS has a solid growth pattern. When terminal duct lobular units are involved, the process can be very difficult to distinguish from lobular carcinoma in situ. Features in favour of DCIS are

II - C - 15


greater cellular cohesion and lack of intracytoplasmic lumina. Occasionally, however, there may be a combination of both processes.

Intermediate Nuclear Grade DCIS Some cases of DCIS cannot be assigned easily to the high or low nuclear grade categories. The nuclei show mild to moderate pleomorphism which is less than that seen in high grade DCIS but they lack the monotony of the small cell type. The nucleus:cytoplasm ratio is often high and one or two nucleoli may be identified. The growth pattern may be solid, cribriform or micropapillary and the cells usually exhibit some degree of polarization covering papillary processes or lining intercellular lumina although this is not as marked as in low nuclear grade DCIS.

Mixed Types A proportion of cases of DCIS exhibit features of more than one histological subtype. One of the advantages of classifying DCIS according to nuclear grade is that, although variations of growth pattern are frequent, there is usually a dominant cell type and the lesion is fairly easily classified into one of the above main groups. Rarely, cells of different nuclear grade may be seen within a single lesion. This should be recorded but the case should be classified according to the highest nuclear grade observed.

Other histological types The main features of encysted papillary carcinoma are listed in Table 1 (see p. 9 ). Ductal carcinoma in situ of signet ring cell, pure apocrine cell, cystic hypersecretory and neuroendocrine types have been described and may be classified separately. For further details of these rare variants, the reader is referred to recent standard textbooks of breast pathology.

Lobular carcinoma The histological features of lobular carcinoma in situ are compared with in situ those of atypical lobular hyperplasia in Table 3 and with ductal carcinoma

in situ in Table 4. To maximize consistency of diagnosis, it is recommended that the term lobular carcinoma in situ be used when the characteristic uniform cells comprise the entire population of the lobular units, that there are no residual lumina and that there is expansion and/or distortion of at least one half the acini in the lobule. Otherwise the lesion should be classified as atypical lobular hyperplasia.

I I - C - 16


TABLE 4. DISTINCTION OF DUCTAL FROM LOBULAR CARCINOMA IN SITU


Cells

Intracytoplasmic lumina

Growth pattern

Cell cohesion

Degree of distension of involved structures

Pagetoid spread into interlobular ducts

Necrosis

Mitoses

Abnormal mitoses

Calcification

Ductal carcinoma in situ

Variable, depending on nuclear grade (see p. 15)

Rare

Very variable, e.g. solid, comedo, papillary, cribriform

Usually good

Moderate to great

Absent

Common with high nuclear grade, uncommon with low nuclear grade

Common with high nuclear grade, uncommon with low nuclear grade

Common with high nuclear grade, rare with low nuclear grade

Common

Lobular carcinoma in situ

Small, rounded with granular or hyperchromatic nuclei, inconspicuous nucleoli and high nucleo-cytoplasmic ratio

Common

Diffuse monotonous with complete luminal obliteration

Usually poor

Slight to moderate

Often present

Absent

Infrequent

Rare

Rare

NB: All the features of a lesion should be taken into account when making a diagnosis. No criterion is reliable alom

Paget's disease In this condition, there are adenocarcinoma cells within the epidermis of the nipple. Cases where there is direct epidermal invasion by tumour infiltrating the skin should be excluded. Paget's disease should be recorded regardless of whether or not an underlying in situ or invasive carcinoma is identified. The underlying carcinoma should be recorded separately. Diagnosing Microinvasion A microinvasive carcinoma is defined for the purposes of the reporting form as a tumour in which the dominant lesion is DCIS but in which there are one or more clearly separate foci of infiltration of non-specialized interlobular or interductal fibrous or adipose tissue, none measuring more than 1 mm (about 2 hpf - see later) in maximal diameter. This definition is very restrictive and tumours fulfilling the criteria are consequently very rare. If there is sufficient doubt about the presence of invasion, the case should be classified as DCIS. Where the evidence is equivocal, tick the 'Microinvasion - Possible' box on the reporting form. Possible microinvasion includes separate islands of appropriately abnormal epithelium which are embedded in periductal fibrosis or inflammation, where the true boundary of the specialized periductal or lobular stroma is not clear. The term 'possible' microinvasion completely excludes merely ultrastructural evidence of basement membrane breach, histochemical or immunohistochemically identified basement membrane discontinuities and lesions in which there is demonstrable continuity in a 5pm section with the parent DCIS. Microinvasion is largely restricted to high nuclear grade types of DCIS, mainly of comedo type. Cases of apparently pure comedo DCIS should thus be extensively sampled

II - C - 17


'Ductal' - no specific type (Ductal-NST)

Infiltrating lobular carcinoma

Tubular carcinoma (including cribriform carcinoma)

Medullary carcinoma

to exclude invasion. Microinvasive carcinomas should likewise be extensively sampled in order to exclude the possibility of larger invasive foci. Where such foci are found, the lesion should be classified as an invasive carcinoma and the approximate number and size range of the invasive foci stated under 'Comments/Additional Information'. Small invasive carcinomas without an in situ component are classified as invasive. Classifying Invasive Carcinoma Typing invasive carcinomas has established prognostic value.16,17 Some caution should be exercised in typing carcinomas in inadequately fixed specimens or if they have been removed from patients who have been treated primarily by chemotherapy or radiotherapy. The more common types are described below. This group contains infiltrating carcinomas which cannot be entered into any type other category on the form, or classified as any of the less common variants of infiltrating breast carcinoma. Consequently, invasive ductal carcinomas exhibit great variation in appearance and are the most common carcinomas, accounting for up to 75% in most series. Infiltrating lobular carcinoma is composed of small regular cells identical to those seen in the in situ form. In its classical form, the cells are dissociated from each other or form single files or targetoid patterns around uninvolved ducts. Several variants have been identified in addition to this classical form but in each case the cell type is the same: a) the alveolar variant exhibits small aggregates of 20 or more cells;18

the solid variant consists of sheets of cells with little stroma;19

the tubulo-lobular type exhibits microtubular formation as part of the classical pattern.20

Tumours that show mixtures of typical tubular and classical lobular carcinoma should be classified as mixed (see below), the pleomorphic variant is uncommon and exhibits the growth pattern of classical lobular carcinoma throughout but the cytological appearances are more pleomorphic. Mixtures of above.

At least 90% of the tumour should exhibit one or more of the above patterns to be classified as infiltrating lobular. Tubular carcinomas are composed of round, ovoid, or angulated single layered tubules in a cellular fibrous or fibro-elastotic stroma. The neoplastic cells are small, uniform and may show cytoplasmic apical snouting. At least 90% of the tumour should exhibit the classical growth pattern to be classified as tubular. If the co-existent carcinoma is solely of the invasive cribriform type, however, then the tumour should be typed as tubular if the tubular pattern forms over 50% of the lesion.

Invasive cribriform carcinoma is composed of masses of small regular cells similar to those seen in tubular carcinoma. The invasive islands, however, exhibit a cribriform rather than a tubular appearance. Apical snouting is often present. More than 90% of the lesion should exhibit the cribriform appearance except in cases where the only co-existent pattern is tubular carcinoma when over 50% must be of the cribriform appearance in order to be so classified. If a diagnosis of cribriform carcinoma is preferred, then tick the 'tubular' box and make the appropriate comment under 'Comments/ Additional Information'. These rare tumours are composed of syncytial interconnecting masses of

b) c)

d)

e)

II - C - 18


Mucinous carcinoma

Mixed tumours

Other primary carcinoma

Other malignant tumour

Not assessable

large pleomorphic cells with vesicular nuclei and prominent nucleoli; they are of histological grade 3. The stroma may be sparse but always contains large numbers of lymphoid cells. The border of the tumour is well-defined. The whole tumour must exhibit these features to be typed as medullary. Surrounding in situ elements are very uncommon. The term atypical medullary carcinoma may be specified under 'other primary carcinoma' for lesions which do not fulfil all the criteria for medullary carcinoma. The atypical medullary group has been defined by both Fisher et al.21 and Ridolfi et al.22 These tumours show less lymphoid infiltration, less circumscription or areas of dense fibrosis while still having the other features of a medullary carcinoma. A well circumscribed tumour is also classified as atypical medullary if up to 25% is composed of 'ductal' type and the rest comprises classical medullary carcinoma. If in doubt, classify as 'Ductal-NST'. This type is also known as mucoid, gelatinous or colloid carcinoma. There are islands of uniform small cells in lakes of extracellular mucin. An in situ component is uncommon. At least 90% of the tumour must exhibit the mucinous appearance to be so classified. Tubular or cribriform mixed carcinomas have a usually central tubular or cribriform zone, which amounts to 75-90% of the area, with a ductal-NST or infiltrating lobular component usually at the periphery accounting for the remainder.23 Such tumours have a good prognosis but less so than the pure types. The mixed NST and mucinous carcinomas include any mixtures of mucinous with ductal NST where the former accounts for 10-90%. In mixed NST and lobular carcinomas distinct and separate ductal NST and lobular elements must be present; the former occupies between 10% and 90% of the tumour area. These tumours are regarded as biphasic and are distinct from mixed and pleomorphic lobular carcinomas (see above). Mixtures of NST and specific types not listed on the form should be classified as 'other primary carcinoma'. Other primary breast carcinomas should be entered under this heading and will include variants such as atypical medullary, spindle cell, infiltrating papillary, argyrophil, secretory, apocrine, etc. Please include non-epithelial tumours and secondary carcinomas in this category. For purposes of convenience, all high grade phyllodes tumours should be recorded here. This category should be ticked only if an invasive carcinoma cannot be assigned to any of the previous groups for technical reasons, e.g. the specimen is too small or poorly preserved.

Recording Prognostic Data

Maximum diameter All lesions should be measured in the fresh or fixed state and on the histological preparation. If the two measurements are discrepant then that obtained from histological examination should be recorded where tumours are small enough to be visualized in cross-section. This may give a small underestimation of size due to shrinkage of the tissue in processing. It is considered, however, that the slight but consistent underestimation in the size of all tumours is preferable to the larger and less predictable errors that may result from measuring poorly delineated tumours macroscopically. Clearly, sufficient blocks should be taken from the periphery of larger

II-c


tumours to allow accurate estimates of their size to be made from combined histological and macroscopic examination. The largest dimension should be recorded to the nearest millimetre. For non-invasive carcinomas, the maximum diameter should be entered in the 'Non-Invasive' section only where the tumour is of ductal type; lobular carcinoma in situ is not measured. For invasive carcinomas, the invasive component only needs to be recorded unless accompanying ductal carcinoma in situ extends more than 1mm beyond the periphery of the infiltrative component, when the size of the infiltrative component and the overall size should be stated in the appropriate spaces of this section. This is to allow the identification of invasive carcinomas, where the in situ component forms a significant proportion of the lesion and may be important in determining the risk of recurrence after local excision. The largest dimension, to the nearest millimetre, is recorded in each case. The diagrams below illustrate whole and invasive tumour measurements in a variety of circumstances. Foci of lymphatic and blood vascular invasion are not included in the whole tumour measurement.

D

a a e

Invasive Tumours I = Invasive Tumour Measurement

= Ductal Carcinoma in Situ W = Whole Tumour Measurement

In E the satellite focus of invasive tumour is not included in the measurement

In F the best estimate of the total size of the invasive components is given

II - C - 20


Lymph nodes

Excision

Grade

If a carcinoma (either infiltrative or ductal in situ) is insufficiently delineated to measure reliably, make an appropriate comment in the 'Comments/Additional Information' section and give an approximate estimate of the maximum dimension of the area over which the changes extend. It may be necessary to use combined histological, macroscopic and radiological information to make a reliable estimate. All lymph nodes should be examined histologically. The use of immunohistology is most appropriate in cases where there is doubt about the presence of small metastases. The clinical relevance of metastases detected solely by this means remains controversial. Please record data from axillary nodes separately from nodes from other sites. The presence of extracapsular spread can be noted under 'Comments/Additional Information'. For infiltrative tumours, the distance from the nearest resection margin should be recorded and checked from the histological sections. Other margins can be reported if required. This normally refers to the infiltrative component but, if associated ductal carcinoma in situ extends nearer to the margin than the infiltrative component, then enter its distance from the margin and state in the 'Comments' section that this measurement refers to the in situ component. The information should be related to orientation markers if used. For pure ductal carcinoma in situ, the distance from the nearest excision margin should be recorded if the lesion is sufficiently delineated. If not, make a comment under 'Comments/Additional Information'. The presence of nonneoplastic breast parenchyma between the DCIS and the margin is usually associated with adequate excision. The specimen radiograph is also a useful adjunct in assessing surgical clearance. In cases where the adequacy of excision is uncertain, please tick the relevant box and state the reason for uncertainty under 'Comments/Additional Information'. See earlier for guidance on macroscopic examination. Grading can provide powerful prognostic information. It requires some commitment and strict adherence to a recommended protocol. The following protocol is based on that described by Elston & Ellis.24 The method involves the assessment of three components of tumour morphology: tubule formation, nuclear pleomorphism and frequency of mitoses. Each is scored from 1-3. Adding the scores gives the overall histological grade as shown below.

Tubule formation 1 ) majority of tumour (greater than 75%) 2) moderate amount (10-75%) 3) little or none (less than 10%)

Nuclear pleomorphism 1) nuclei small, with little increase in size in comparison with normal

breast epithelial cells, regular outlines, uniform nuclear chromatin, little variation in size.

2) cells larger than normal with open vesicular nuclei, visible nucleoli and moderate variability in both size and shape.

3) vesicular nuclei, often with prominent nucleoli, exhibiting marked variation in size and shape, occasionally with very large and bizarre forms.

II - C - 21


edition (JUNE 1996)

Mitoses

The size of high power fields is very variable and hence it is necessary to

standardize the mitotic count using the graph below. In order to determine

the mitotic count for an individual microscope, the following procedure should

be adopted:

Mitotic count

28

26

24

22

20

18

16

14

12

10

8

6

4

2

0

Graph of mitotic counts by field diameter

i

ι

ïCQI θ 3

|

ì

Seo

Ι ι

ι i ! i

ιτβ-2

!

ι

S^oreh

ι · ! t

Ι '-

i I ' I i 1

! i i i ; ; ; ι i i 1 i i : ! ¡ —

0.44 0.46 0.48 0.50 0.52 0.54 0.56 0.58 0.60 0.62

Field diameter

1. measure the field diameter of the microscope with a graticule.

2. plot this value on the vertical axis of the graph.

3. draw a vertical line at this value.

4. read off the value a on the horizontal axis where the line intersects

the lower bold line.

5. read of the value b on the horizontal axis where the line intersects

the upper bold line.

6. the count is then

Score Count

3 >b

2 between a+1 and b

1 Oto a

For example, for a field diameter of 0.48, a=6, b=12 from graph - therefore

Score 3 = >12 mitoses/1 Ohpf

Score 2 = 7-12 mitoses/1 Ohpf

Score 1 = 0-6 mitoses/1 Ohpf

This needs to be done only once for each microscope.

n - c - 22


Disease extent

Overall grade The scores for tubule formation, nuclear pleomorphism and mitoses are then added together and assigned to grades as below: Grade 1 = score 3-5 Grade 2 = score 6-7 Grade 3 = score 8-9 It is recommended that grading is not restricted to invasive carcinoma NST but is undertaken on all histological subtypes. There are two major reasons for this recommendation: 1) there are occasionally problems in deciding whether to classify a tumour as NST or some other type 2) there may be significant variation within certain subtypes, e.g. invasive lobular carcinoma. Tick 'Not assessable' if for any reason the grade cannot be determined, e.g. specimen poorly preserved or too small. It must be clearly stated if a grading system other than that described above is used. The term 'localized' is used to describe a single focus of tumour with defined borderlines of any size. It should also be used where the exent of the tumour cannot accurately be defined although all of it appears to be part of a single lesion.

Vascular invasion

Comments/ Additional information

The term 'multiple' is used to describe multiple foci of in situ or infiltrating carcinoma which are widely separated (at least 40mm) and present in quadrants or segments other than that of the main tumour. 'Multiple' is preferred to 'multifocal' or 'multicentric' as there is currently a lack of agreement on how these terms should be used. Tick 'Not assessable' if the extent of the disease cannot be determined or if it is not clear whether the tumour is localized or multiple. The presence of unequivocal tumour in vascular spaces should be recorded. If there is doubt about diagnosing vascular invasion, please tick the 'not seen' box. The difficulty in identifying small blood vessels as blood or lymphatic precludes accurate recording of their type and specification of lymphatic or venous invasion is not required. Ideally, a clear rim of endothelium should be identified around the tumour before vascular invasion is recorded. The use of immunostaining for endothelial markers may be helpful in confirming vascular invasion in difficult cases but is not recommended on a routine basis. Morphological features which may be helpful when diagnosing vascular invasion are: 1) clumps of tumour in spaces outside the main tumour mass are more

likely to indicate vascular invasion. 2) nests of tumour separated from the stroma by shrinkage artefact

usually conform better to the shape of the space in which they lie. 3) the proximity of larger veins and arteries in the diagnosis of

lymphatic invasion. 4) the presence within the space of erythrocytes and/or thrombus. Any relevant additional information may be entered here as free text. Please also state if any further special investigations have been undertaken, e.g. steroid hormone receptor determination, oncogene analysis, etc.

I I - C - 2 3


Histological If normal, tick the normal box and do not complete the rest of the form. diagnosis 'Normal' includes minimal alterations such as fibrosis and microscopic

dilatation of acini or ducts, lobular involution and enlargement and blunt duct adenosis. If malignant and benign changes are found, tick only the malignant box. Tick the benign box when the breast is neither normal nor exhibits malignancy.

References

1. Andersen J, Poulsen HS. Immunohistochemical oestrogen receptor determination in paraffin-embedded tissue: prediction of response to hormonal treatment in advanced breast cancer. Cancer 1989;64:1901-1908.

2. Snead DRJ, Bell JA, Dixon AR, Nicholson RI, Elston CW, Blarney RW, Ellis IO. Methodology of immunohistological detection of oestrogen receptor in human breast carcinoma in formalin-fixed, paraffin-embedded tissue: a comparison with frozen section methodology. Histopathology 1993;23:233-238.

3. Anderson TJ. Breast cancer screening: principles and practicalities for histopathologists. Recent Advances in Histopathology No. 14, 43-61, Churchill Livingstone 1989.

4. Armstrong JS, Davies JD. Laboratory handling of impalpable breast lesions: A review. J. Clin. Pathol. 1991;44:89-93.

5. Department of Health Medical Devices Directorate. Evaluation of specimen radiography cabinets: reports and guidance notes. Blue book (MDD/91/13) London: Department of Health, 1991, 1-33 and 1-13.

6. Schnitt SJ, Wang HH. Histologic sampling of grossly benign breast biopsies: how much is enough? Am J Surg Pathol 1989;13:505-512.

7. Gad A. Pathology in breast cancer screening: A 15-year experience from a Swedish programme. In: Breast Cancer Screening in Europe. A. Gad & M. Rosselli del Turco (eds), Springer-Verlag 1993,87-101.

8. Frappait L, Boudeulle M, Boumendil J et al. Structure and composition of microcalcifications in benign and malignant lesions of the breast. Human Pathol 1984;15:880-889.

9. Nielsen BB. Adenosis tumour of the breast - a clinicopathological investigation of 27 cases. Histopathology 1987;11:1259-1275.

10. Simpson JF, Page DL, Dupont WD. Apocrine adenosis: a mimic of mammary carcinoma. Surg Pathol 1990;3:289-299.

11. Page DL, Rogers LW. Combined histologic and cytologic criteria for the diagnosis of mammary atypical ductal hyperplasia. Human Pathol 1992, 23, 1095-1097.

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12. Böcker W, Bier B, Freytag G, Brömmelkamp B, Jarasch E-D, Edel G, Dockhorn-Dworniczak B, Schmid KW. An immunohistochemical study of the breast using antibodies to basal and luminal keratins, alpha-smooth muscle actin, vimentin, collagen IV and laminin. Part I: normal breast and benign proliferative lesions. Virchows Archiv A Pathol Anat 1992;421:315-322.

13. Lagios MD. Duct carcinoma in situ. Surg Clin N Am 1990, 70, 853-871.

14. Bellamy COC, McDonald C, Salter DM, Chetty U, Anderson TJ. Noninvasive ductal carcinoma of the breast: the relevance of histologic categorization. Human Pathol 1993;24:16-23.

15. Holland R, Peterse JL, Millis RR, Eusebi V, Faverly D, van de Vijver MJ, Zafrani B. Ductal carcinoma in situ: a proposal fora new classification. Semin Diagn Pathol 1994;11:167-180.

16. Page DL, Anderson TJ. Diagnostic Histopathology of the Breast, 1987, pp. 193-268. Churchill Livingstone, Edinburgh, London, Melbourne and New York.

17. Ellis IO, Galea M, Broughton N, Locker A, Blarney RW, Elston CW. Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long term follow-up. Histopathology 1992;20:479-489.

18. Martinez V, Azzopardi JG. Invasive lobular carcinoma of the breast: incidence and variants. Histopathology 1979;3:467-488.

19. Fechner RE. Histologic variants of infiltrating lobular carcinoma of the breast. Human Pathol 1975;6:373-378.

20. Fisher ER, Gregorio RM, Redmond C, Fisher B. Tubulolobular invasive breast cancer: a variant of lobular invasive cancer. Human Pathol 1977;8:679-683.

21. Fisher ER, Gregorio RM, Fisher B, Redmond C, Vellios F, Sommers SC and co-operating investigators. The pathology of invasive breast cancer: a syllabus derived from findings of the National Surgical Adjuvant Breast Project (Protocol No 4). Cancer 1975;36:1-84.

22. Ridolfi RL, Rosen PP, Port A, Kinne D, Mike V. Medullary carcinoma of the breast: a clinicopathologic study with 10-year follow-up. Cancer 1977;40:1365-1385.

23. Pari FF, Richardson LD. The histological and biological spectrum of tubular carcinoma of the breast. Human Pathol 1983;14:694-698.

24. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long term follow up. Histopathology 1991;19:403-410.

II - C - 25


Index for screening office pathology system

Term

A Abscess Adenocarcinoma (no special type) Adenoid cystic carcinoma Adenoma, apocrine Adenoma intraduct Adenoma of nipple Adenoma, pleomorphic Adenoma, tubular 'Adenomyoepithelioma'

Adenosis, NOS Adenosis, apocrine Adenosis, apocrine (atypical)

Adenosis, blunt duct Adenosis, microglandular Adenosis, sclerosing with atypia Adnexal tumours Alveolar variant of lobular carcinoma Aneurysm Angiosarcoma Apocrine adenoma Apocrine adenosis Apocrine carcinoma (in-situ) Apocrine carcinoma (invasive) Apocrine metaplasia (multilayered/papillary) Argyrophil carcinoma Arteritis Atypical blunt duct adenosis

Atypical ductal hyperplasia Atypical epitheliosis (ductal) Atypical lobular hyperplasia

Place to classify on form

Other benign pathology (specify) Invasive ductal n.s.t. Other primary carcinoma (specify) Other benign pathology (specify) Enteras papilloma Other benign pathology (specify) Other benign pathology (specify) Fibroadenoma Other primary carcinoma (specify)

OR Other benign pathology (specify) Histology normal Other benign pathology (specify) Other benign pathology (specify) Epithelial proliferation-atypia (ductal) Histology normal Other benign pathology (specify) Sclerosing adenosis Epithelial proliferation atypia ductal or lobular Other benign pathology (specify) Invasive lobular Other benign pathology (specify) Other malignant tumour (specify) Other benign pathology (specify) Other benign pathology (specify) Non-invasive malignant, ductal (specify) Other primary carcinoma (if pure) or ductal n.s.t. Fibrocystic change Epithelial proliferation present Other primary carcinoma (specify) Other benign pathology (specify) Fibrocystic change Epithelial proliferation-atypia (ductal) Epithelial proliferation-atypia (ductal) Epithelial proliferation-atypia Epithelial proliferation-atypia (lobular)

Β B-cell lymphoma Benign phyllodes tumour Blunt duct adenosis Blunt duct adenosis (atypical) Breast abscess

Other malignant tumour (specify) Other benign pathology (specify) Histology normal Epithelial proliferation-atypia (ductal) Other benign pathology (specify)

n - C - 26


Calcification (benign) Calcification (malignant) Carcinoma, apocrine (in-situ) Carcinoma, apocrine (invasive) Carcinoma, clear cell Carcinoma, colloid Carcinoma, comedo-in-situ Carcinoma, cribriform (in-situ) Carcinoma, cribriform (invasive) Carcinoma, ductal in-situ Carcinoma, lobular in-situ Carcinoma, lobular (invasive) Carcinoma, lobular variant Carcinoma, medullary Carcinoma, metastatic Carcinoma, mixed Carcinoma, mucinous Carcinoma, papillary Carcinoma, signet ring Carcinoma, spindle cell Carcinoma, squamous Carcinosarcoma Cellular fibroadenoma Clear cell carcinoma Clear cell hidradenoma Clear cell metaplasia Collagenous spherulosis Comedocarcinoma Comedocarcinoma invasive Complex sclerosing lesion Cribriform carcinoma (in-situ) Cribriform carcinoma (invasive) Cyclical menstrual changes Cyst, epidermoid Cyst, single Cyst, multiple Cystic disease Cystic mastopathia Cystic hypersecretory hyperplasia Cystic hypersecretory carcinoma

Calcification present, benign Calcification present, malignant Non-invasive malignant, ductal (specify type) Other primary carcinoma (if pure) or ductal n.s.t. Other primary carcinoma (specify) Invasive mucinous carcinoma Non-invasive malignant, ductal (specify type) Non-invasive malignant, ductal (specify type) Invasive tubular or cribriform Non-invasive malignant, ductal (specify sub-type) Non-invasive malignant, lobular Invasive lobular Invasive lobular Invasive medullary Other malignant tumour (specify) Other primary carcinoma (specify types) Invasive mucinous carcinoma Other primary carcinoma (specify) Other primary carcinoma (specify) Other primary carcinoma (specify) Other primary carcinoma (specify) Other primary carcinoma (specify) Fibroadenoma Other primary carcinoma (specify) Other benign pathology (specify) Other benign pathology (specify) Other benign pathology (specify) Non-invasive malignant, ductal Invasive ductal n.s.t. Complex sclerosing lesion/radial scar Non-invasive malignant, ductal (specify type) Invasive tubular or cribriform Histology normal Other benign pathology (specify) Solitary cyst Fibrocystic change Enter components Enter components Other benign pathology (specify) Non-invasive malignant, ductal

Ductal carcinoma in-situ Ductal carcinoma invasive Ductal hyperplasia (regular) Ductal hyperplasia (atypical) Duct ectasia Duct papilloma Dysplasia, mammary

Non-invasive malignant, ductal Invasive ductal n.s.t. Epithelial proliferation present without atypia Epithelial proliferation, atypical (ductal) Periductal mastitis/duct ectasia Papilloma, single Enter components

II - C - 27


Eccrine tumours Epidermoid cyst Epitheliosis (regular) Epitheliosis (atypical) Epitheliosis (infiltrating)

Other benign pathology (specify) Other benign pathology (specify) Epithelial proliferation present without atypia Epithelial proliferation, atypical (ductal) Complex sclerosing lesion/radial scar

Fat necrosis Fibroadenoma Fibroadenoma, giant Fibroadenoma, juvenile Fibrocystic disease Fibromatosis Fistula, mammillary Focal lactational change Foreign body reaction

Other benign pathology (specify) Fibroadenoma Fibroadenoma Fibroadenoma Enter components Other benign pathology (specify) Other benign pathology (specify) Histology normal Other benign pathology (specify)

Galactocoele Giant fibroadenoma Glycogen-rich carcinoma Grading of carcinomas Granulomatous mastitis

H Haematoma Haemangioma Hamartoma Hyaline epithelial inclusions Hyperplasia, ductal (regular) Hyperplasia, ductal (atypical) Hyperplasia, lobular (= adenosis) Hyperplasia, lobular (atypical)

I Infarct 'Inflammatory carcinoma' Invasive carcinoma Invasive comedocarcinoma Invasive cribriform carcinoma Involution

Other benign pathology (specify) Fibroadenoma Other primary carcinoma (specify) See page Other benign pathology (specify)

Other benign pathology (specify) Other benign pathology (specify) Other benign pathology (specify) Other benign pathology (specify) Epithelial proliferation present without atypia Epithelial proliferation-atypia (ductal) Histology normal Epithelial proliferation-atypia (lobular)

Other benign pathology (specify) Specify by type (usually ductal n.s.t.) Specify by type Invasive ductal n.s.t. Invasive tubular or cribriform Histology normal

Juvenile fibroadenoma Juvenile papillomatosis

Fibroadenoma Other benign pathology (specify)

n - c - 28


L Lactation Lactational change, focal Lipoma Lipid-rich carcinoma Lobular carcinoma in-situ Lobular carcinoma invasive Lobular hyperplasia (= adenosis) Lobular hyperplasia (atypical) Lymphoma

M Malignant phyllodes tumour Mammary duct ectasia Mammillary fistula Mastitis, acute Mastitis, granulomatous Mastitis, plasma cell Mastopathia, cystic Medullary carcinoma Menopausal changes Metaplasia, apocrine (single layer) Metaplasia, apocrine (multilayered/papillary) Metaplasia, clear cell Metaplasia, mucoid Metaplasia, squamous Metastatic lesion Microcysts Microglandular adenosis Microinvasive carcinoma Micropapillary change Mixed carcinoma Mondar's disease Mucinous carcinoma Mucoele-like lesion Mucoid metaplasia Multiple papilloma syndrome Multiple papilloma syndrome with atypia Myoepithelial hyperplasia

N Necrosis, fat Nipple adenoma Nipple - Paget's disease Normal breast

Histology normal Histology normal Other benign pathology (specify) Other primary carcinoma (specify) Non-invasive malignant, lobular Invasive lobular Histology normal Epithelial proliferation-atypia (lobular) Other malignant tumour (specify)

Other malignant tumour (specify) Periductal mastitis/duct ectasia Other benign pathology (specify) Other benign pathology (specify) Other benign pathology (specify) Periductal mastitis/duct ectasia Enter components Invasive medullary Histology normal Fibrocystic change Fibrocystic change Epithelial proliferation present Other benign pathology (specify) Other benign pathology (specify) Other benign pathology (specify) Other malignant tumour (specify) Histology normal Other benign pathology (specify) Code by in-situ component and specify microinvasion present Epithelial proliferation present Other primary carcinoma (specify types) Other benign pathology (specify) Invasive mucinous carcinoma Other benign pathology (specify) Other benign pathology (specify) Papilloma, multiple Papilloma, multiple Epithelial proliferation-atypia (ductal) Other benign pathology (specify)

Other benign pathology (specify) Other benign pathology (specify) Non-invasive malignant Paget's disease Histology normal

II - C - 29


Paget's disease of nipple Non-invasive malignant, Paget's disease Panniculitis Papillary carcinoma (in-situ) Papillary carcinoma (invasive) Papilloma, duct Papillomatosis Papillomatosis, juvenile Papillomatosis, sclerosing Phyllodes tumour (low grade) Phyllodes tumour (high grade) Pregnancy changes

R Radial scar Regular hyperplasia

Non-invasive malignant, Paget's disease Other benign pathology (specify) Non-invasive malignant, ductal (specify type) Other primary carcinoma (specify) Papilloma Epithelial proliferation (with or without atypia) Other benign pathology (specify) Specify under other benign pathology as adenoma of nipple Other benign pathology (specify) Other malignant tumour (specify) Histology normal

Complex sclerosing lesion/radial scar Epithelial proliferation present without atypia

Sarcoidosis Sarcoma Sclerosing adenosis Sclerosing adenosis with atypia Sclerosing subareolar proliferation Squamous carcinoma Squamous metaplasia Spindle cell carcinoma Scar, radial

Τ Trauma Tuberculosis Tubular adenoma Tubular carcinoma

W Wegener's granulomatosis

Other benign pathology (specify) Other malignant tumour (specify) Sclerosing adenosis Sclerosing adenosis Epithelial proliferation-atypia Specify under other benign pathology as adenoma of nipple Invasive malignant, other (specify) Other benign pathology (specify) Invasive malignant, other (specify) Complex sclerosing lesion/radial scar

Other benign pathology (specify) Other benign pathology (specify) Fibrodenoma Invasive malignant, tubular or cribriform

Other benign pathology (specify)

I I - C - 3 0


MEMBERSHIP OF WORKING GROUP Chairman: Prof. J.P. Sloane, University of Liverpool, United Kingdom.

Dr. I. Amendoeira, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.

Dr. N. Apostolikas, Hellenic Anticancer Institute, Athens, Greece.

Professor J.P. Bellocq, Hôpital de Hautepierre, Strasbourg, France.

Dr. S. Bianchi, Italian Breast Screening Programme and Istituto di Anatomia e Istologia Patologica, Firenze, Italy.

Professor W. Böcker, Gerhard-Domagk-Institut für Pathologie, Münster, Germany.

Professor G. Bussolati, Istituto di Anatomia e Istologia Patologica, Torino, Italy.

Dr. CE. Connolly, Associate Professor of Pathology, University Colige Hospital, Galway, Ireland.

Dr. C. De Miguel, Hospital Virgen del Camino, Pamplona, Spain.

Professor P. Dervan, The Eccles Breast Screening Project, Mater Hospital and University College, Dublin, Ireland.

Dr. R. Drijkoningen, Pathologische Ontleedkunde 1, Leuven, Belgium.

Dr. CW. Elston, City Hospital, Nottingham, United Kingdom.

Dr. D. Faverly, Projet Bruxellois de Dépistage du Cancer du Sein and CM.P. Laboratory, Bruxelles, Belgium.

Dr. A. Gad, Falun Hospital, Falun, Sweden.

Dr. R. Holland, National Expert and Training Centre for Breast Cancer Screening, Nijmegen, The Netherlands.

Dr. J. Jacquemier, Institut Paoli Calmette and Breast Histological Registry, Marseille, France.

Dr. M. Lacerda, Centro de Oncologia de Coimbra, Coimbra, Portugal.

Dr. A. Lindgren, University Hospital, Uppsala, Sweden.

Dr. J. Martinez-Peñuela, Hospital de Navarra, Pamplona, Spain.

Dr. J.L. Peterse, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Dr. F. Rank, Bispebjerg Hospital and Danish Cancer Society, Copenhagen, Denmark.

Dr. V. Tsakraklides, Hygeia Hospital, Athens, Greece.

Dr. C de Wolf, European Commission, Luxembourg.

Dr. B. Zafrani, Institut Curie, Paris, France.

II - C - 31

European Protocol for the

QUALITY CONTROL

of the Physical and Technical Aspects

of Mammography Screening

Appendix to

"European Guidelines for Quality Assurance in Mammography Screening"

JUNE 1996

EUROPEAN COMMISSION

• Europe Against Cancer Programme · Radiation Protection Actions

The European Protocol for the

Quality Control of the Physical and Technical Aspects

of Mammography Screening

EUROPEAN COMMISSION

• DG V F.2 Europe Against Cancer · • DG XI C.1 Radiation Protection Actions · • DG XII F.6 Radiation Protection Actions ·

Authors:

Martin A.O. Thijssen, Nijmegen NL Kenneth C. Young, Guildford UK

Sander van Woudenberg, Nijmegen NL

Revisors: KR. Bijkerk, Nijmegen, NL

A. Ferro de Carvalho, Lisbon, Ρ M. Fitzgerald, London, UK A. Flioni-Vyza, Athens, GR R. Van Loon, Brussels, BE

revision: JUNE 1996

In collaboration with the Study Group on Quality Control in Mammography:

D.R. Dance, London UK A. Ferro de Carvalho, Lisbon, A. Flioni Vyza, Athens, GR M. Gambaccinl, Ferrara, I W. Leltz, Stockholm, S C. Maccia, Cachan, F

B.M. Moores, Liverpool, UK H. Schibilla, Brussels, EC F.E. Stieve, Neuherberg, D D.H.A.P. Teunen, Luxembourg, EC M.A.O. Thijssen, Nijmegen, NL E. Vano, Madrid, E J. Zoetelief, Rijswijk, NL

This document is the first revision of chapter 4, "Technical Aspects" in the "European Guidelines for Quality Assurance in Mammography Screening", published in 1993 (EUR 14821, ISSN 1018-5593). Original authors: Johan M. Lindeijer, NL t . Remko Bijkerk, NL Martin A. O. Thijssen, NL

Contents

D- THE EUROPEAN PROTOCOL FOR THE QUALITY CONTROL OF THE PHYSICAL AND TECHNICAL ASPECTS OF MAMMOGRAPHY SCREENING

Executive summary

1. Introduction to the measurements

D-1

D-3

Description of the measurements 2.1 X-ray generation and control I

2.1.1 X-ray source I Focal spot size I Focal spot size: star pattern method I Focal spot size, slit camera method I Focal spot size, pinhole method I Source-to-image distance I Alignment of X-ray field/image receptor I Radiation leakage I Tube output I

2.1.2 Tube voltage I Reproducibility and accuracy I Half Value Layer I

2.1.3 AEC-system I Optical density control setting: central value and difference per step I Guard timer I Short term reproducibility II Long term reproducibility II Object thickness compensation II Tube voltage compensation II

2.1.4 Compression II Compression force II Compression plate alignment II

2.2 Bucky and image receptor II 2.2.1 Anti scatter grid II

Grid system factor II Grid imaging II -

2.2.2 Screen-film II -Inter cassette sensitivity and attenuation variation II -Screen-film contact II -

2.3 Film processing II -2.3.1 Base line performance processor II -

Temperature II -Processing time II -

2.3.2 Film and processor II -Sensitometry II -Daily performance II -Artifacts II -

2.3.3 Darkroom II -Light leakage II -Safelights II -Film hopper II -Cassettes II -

-D -D -D -D -D -D -D - D - 7 - D - 7 - D - 7 - D - 7 - D - 8 - D - 8 - D - 8 - D - 9 - D - 9 - D - 9 D-10 D-10 D-10 D-10 D-10 D -11 D - 11 D-12 D-12 D-12 D-12 D-12 D-12 D-12 D-14 D-14 D-14 D-14 D-14 D-14 D-15 D-15 D-15 D-15 D-16 D-16 D-16

I I - D

2.4 Viewing conditions II - D -17 2.4.1 Viewing box II - D -17

Luminance II - D -17 Homogeneity II - D -17

2.4.2 Ambient light II - D -18 Level II - D -18

2.5 System properties II - D -19 2.5.1 Dosimetry II - D -19

Entrance surface air kerma II - D -19 2.5.2 Image Quality II - D -19

Spatial resolution I I - D - 1 9 Image contrast II - D - 20 Threshold contrast visibility II - D - 20 Exposure time II - D - 20

3. Daily and weekly QC tests II - D - 21

4. Definition of terms II - D - 22

5. Tables II - D - 26

6. Bibliography II - D - 29

Appendix 1 : Calculation of film-parameters II - D - 33

Appendix 2: A method to correct for the film curve II - D - 34

Appendix 3: Typical values for other spectra and densities II - D - 35

Appendix 4: Sample Data Sheets II - D - 37

π - D


edition (JUNE 1996)

II - D- THE EUROPEAN PROTOCOL FOR THE QUALITY CONTROL OF THE

PHYSICAL AND TECHNICAL ASPECTS OF M A M M O G R A P H Y SCREENING

Executive summary

A prerequisite for a successful screening project is that the mammograms contain sufficient diagnostic

information to be able to detect breast cancer, using as low a radiation dose as is reasonably achievable

(ALARA). This quality demand holds for every single mammogram. Quality Control (QC) therefore must

ascertain that the equipment performs at a constant high quality level.

In the framework of "Europe Against Cancer" (EAC), a European approach for mammography screening

is chosen to achieve comparable high quality results for all centres participating in the mammography

screening programme. Within this programme, Quality Assurance (QA) takes into account the medical,

organizational and technical aspects. This section is specifically concerned with the quality control of

physical and technical aspects and the dosimetry.

The intention of this part of the guidelines is to indicate the basic test procedures, dose measurements

and their frequencies. The use of these tests and procedures is essential for ensuring high quality

mammography and comparison between centres. This Document is intended as a minimum standard for

implementation throughout the EC Member States and does not reduce more comprehensive and refined

requirements for QC that are specified in local or national QA Programmes. Therefore some screening

programmes may implement additional procedures.

Quality Control (QC)

Mammography screening should only be performed using modern dedicated X-ray equipment and

appropriate image receptors.

QC of the physical and technical aspects in mammography screening starts with specification and

purchase of the appropriate equipment, meeting accepted standards of performance. Before the system

is put into clinical use, it must undergo acceptance testing to ensure that the performance meets these

standards. This holds for the mammography X-ray equipment, image receptor, film processor and QC test

equipment. After acceptance, the performance of all equipment must be maintained above the minimum

level and at the highest level possible.

The QC of the physical and technical aspects must guarantee that the following objectives are met:

1. The radiologist is provided with images that have the best possible diagnostic information obtainable

when the appropriate radiographic technique is employed. The images should at least contain the

defined acceptable level of information, necessary to detect the smaller lesions (see CEC Document

EUR 16260).

2. The ¡mage quality is stable with respect to information content and optical density and consistent with

that obtained by other participating screening centres.

3. The breast dose is As Low As Reasonably Achievable (ALARA) for the diagnostic information required.

QC Measurements and Freguencies

To attain these objectives, QC measurements should be carried out. Each measurement should follow

a written QC protocol that is adapted to the specific requirements of local or national QA programmes. The

European Protocol for the Quality Control of the Physical and Technical Aspects of Mammography

Screening gives guidance on individual physical, technical and dose measurements, and their

frequencies, that should be performed as part of mammography screening programmes.

I I - D - ι


Several measurements can be performed by the local staff. The more elaborate measurements should be undertaken by medical physicists who are trained and experienced in diagnostic radiology and specifically trained in mammography QC. Comparability and consistency of the results from different centres is best achieved if data from all measurements, including those performed by local technicians or radiographers are collected and analyzed centrally.

Image quality and breast dose depend on the equipment used and the radiographic technique employed. QC should be carried out by monitoring the physical and technical parameters of the mammographie system and its components. The following components and system parameters should be monitored:

• X-ray generator and control system; • Bucky and image receptor; • Film processing; • System properties (including dose); • Viewing conditions

The probability of change and the impact of a change on image quality and on breast dose determine the frequencies at which the parameters should be measured. The protocol gives also the basic and desirable limiting values for some QC parameters. The basic values indicate the minimal performance limits. The desirable values indicate the limits that are achievable. New equipment must meet the desirable limits. Limiting values are only indicated when consensus on the measurement method and parameter values has been obtained. The necessary QC equipment for both the basic and desirable level of QC is listed also, together with the appropriate tolerances.

Methods of dosimetry are described in the "European Protocol on Dosimetry in Mammography" (EUR16263). It provides accepted indicators for breast dose, both by measurements on a group of women and by phantom measurements. The summary of this document is listed in annex.

The first (1992) version of this document (REF: EUR 14821) was produced by a Study Group, selected from the contractors of the CEC Radiation Protection Actions. This revised (1996) version is based on a critical review of recent QA and QC literature and includes the experience gained by users of the document and comments from manufacturers of equipment and film-screen systems (see literature and reference list, Chapter 6, bibliography). Communication on this protocol can be directed to the EUREF Coordinating Office, National Expert and Training Centre for Breast Cancer Screening, PO-box 9101, NL-6500 HB Nijmegen, The Netherlands, Tel: +31-(0)24-3617515.

II - D - 2


edition (JUNE 1996)

1 Introduction to the measurements

This protocol is intended to provide the basic techniques for the quality control (QC) of the physical and

technical aspects of mammography screening. It is based on other existing protocols (see chapter 6,

bibliography) and the experience of groups performing QC of mammography equipment. Since the

technique of mammographie imaging and the equipment used are constantly improving, the protocol

needs to be updated regularly.

Many measurements are performed using an exposure of a test object or phantom. All measurements are

performed under normal working conditions: no special adjustments of the equipment are necessary.

Two types of exposures need to be mentioned:

- The reference exposure is intended to provide the information of the system under defined

conditions, independent of the clinical settings.

- The routine exposure is intended to provide the information of the system under clinical conditions,

dependent on the settings that are clinically used.

For the production of the reference or routine exposure, a plexiglass phantom is exposed and the machine

settings are as follows (unless otherwise mentioned):

Reference exposure: Routine exposure:

tube voltage

compression device

plexiglass phantom

■ anti scatter grid

source-to-image distance

phototimer detector

automatic exposure control

• optical density control

28 kV

in contact with phantom

45 mm

present

matching with focused grid

in position closest to chest wall

on, central density step

central position

clinical setting

in contact with phantom

45 mm

present

matching with focused grid

clinical setting

on

clinical setting

The optical density (OD) of the processed image is measured at the reference point, which lies 60 mm

from the chest wall side and laterally centred. The reference optical density is 1.0 OD, base and fog

excluded. Therefore the aim of the measured OD value in the reference point is: 1.0 ± 0.1 + base + fog

(OD). The routine OD may be different.

All measurements should be performed with the same cassette to rule out differences between screens

and cassettes.

Limits of acceptable performance are given, but often a better result would be desirable. Both the

acceptable and desirable limits are given in chapter 5, table 1. Occasionally no limiting value is given, but

only a typical value as an indication.

The measurement frequencies indicated in the table are the minimum required. When problems occur,

additional measurements should be performed to determine the origin of the observed problem and

appropriate actions should be taken to solve the problem.

For guidance on the specific design and operating criteria of suitable test objects; see the Proceedings

of the CEC Workshop on Test Objects (see chapter 6, Bibliography). The definition of terms, like the

reference point and the reference density are given in chapter 4. The evaluation of the results of the QC

measurements can be simplified by using the completion forms provided in appendix 4.

Π - D - 3


Staff and equipment

Several measurements can be performed by the local staff. The more elaborate measurements should be undertaken by medical physicists who are trained and experienced in diagnostic radiology and specifically trained in mammography QC. Comparability and consistency of the results from different centres is best achieved if data from all measurements, including those performed by local technicians or radiographers are collected and analyzed centrally.

The staff conducting the daily/weekly QC-tests will need the following equipment" at the screening site:

- Sensitometer - Densitometer - Thermometer - PMMA plates** - Daily QC test object - Reference cassette

The medical physics staff conducting the other QC-tests will need the following additional equipment":

- Dosemeter - Stopwatch - kVp-meter - Film/screen contact test device - Exposure time meter - Tape measure - Light meter - Compression force test device - QC test objects - Rubber foam - Aluminium sheets - Lead sheet - Focal spot test device + stand - Aluminium stepwedge

The specifications of the listed equipment are given, where appropriate, in chapter 5, table 2. PMMA (polymethylmethacrylate) is commercially available under several brandnames, e.g. Lucite, plexiglass and perspex.

π - D - 4


2 Description of the measurements

2.1 X-ray generation and control

2.1.1 X-ray source

The measurements to determine the focal spot size, source-to-image distance, alignment of X-ray field and image receptor, radiation leakage and tube output, are described in this section.

Focal spot size

The measurement of the focal spot size is intended to determine its physical dimensions at installation or when resolution has markedly decreased. For routine quality control the evaluation of spatial resolution is considered adequate.

The focal spot dimensions can be obtained by using one of the following three methods. • star pattern method; a convenient method (routine testing); • slit camera; a complex, but accurate method for exact dimensions (acceptance testing) • pinhole camera; a complex, but accurate method to determine the shape (acceptance testing)

A magnified X-ray image of the test device is produced using a non-screen cassette. This can be achieved by placing a black film (OD ;> 3) between screen and film. Select the focal spot size required, 28 kV tube voltage and a focal spot charge (mAs) to obtain an optical density between 0.8 and 1.4 OD base and fog excluded (measured in the central area of the image). The device should be imaged at the reference point of the image plane, which is located at 60 mm from the chest wall side and laterally centred. Remove the compression device and use the test stand to support the test device. Select about the same focal spot charge (mAs) that is used to produce the standard image of 45 mm PMMA, which will result in a optical density of the starpattern image: 0.8<OD<1.4. According the IEC/NEMA norm, an 0.3 focal spot is limited to a width of 0.45 mm and a length of 0.65 mm. An 0.4 focal spot is limited to 0.60 and 0.85 mm respectively. No specific limiting value is given here: the measurement of imaging performance of the focal spot is incorporated in the limits for spatial resolution at high contrast, (see 2.5.2)

Focal spot size: star pattern method

The focal spot dimensions can be estimated from the 'blurring diameter' on the image (magnification 2.5 to 3 times) of the star pattern. The distance between the outermost blurred regions is measured in two directions: perpendicular and parallel to the tube axis. Position the cassette on top of the bucky (no grid). The focal spot is calculated by applying formula 2.1, which can also be found in the completion form.

r ΠΧθ v Dblur

1 = * (2.1) 180 (Ms(ar-1)

where θ is the angle of the radiopaque spokes, and Db!ur is the diameter of the blur.

I I - D - 5


edition (JUNE 1996)

The magnification factor (Mstar) is determined by measuring the diameter of the star pattern on the

acquired image (D,mage) and the diameter of the device itself (Dstar), directly on the star, and is

calculated by:

M s t a r=

D ¡ m a g e A t a r (22)

Limiting value None

Frequency At acceptance and when resolution has changed.

Equipment Star resolution pattern (spoke angle 1° orO. 5°) and appropriate test stand.

Focal spot size, slit camera method

To determine the focal spot dimensions (f) with a slit camera, a 10 pm slit is used. Produce two

magnified images (magnification 2.5 to 3 times) of the slit, perpendicular and parallel to the tube axis.

Remove the compression device and use the test stand to support the slit.

The dimensions of the focal spot are derived by examining and measuring the pair of images

through the magnifying glass. Make a correction for the magnification factor according to f=F/MS|it,

where F is the width of the slit image. The magnification factor (Μ5Ν,) is determined by measuring

the distance from the slit to the plane of the film (dsliWo.fiim) and the distance from the focal spot to the

plane of the slit (dfoca, spoMo.slit). Mslit is calculated by:

Msl i t dsi i t-to-f i lm'dfocal SDot-to-slit (2.3)

Note: Mslit = Mimage -1

Remark: The method requires a higher exposure than the star pattern and slit camera methods.

Limiting value None


Equipment Slit camera (10 μ m slit) with appropriate test stand and magnifying glass (5-1 Ox),

having a built-in graticule with 0.1 mm divisions.

Focal spot size, pinhole method

To determine the focal spot dimensions (f) with a pinhole, a 30 pm gold/platinum alloy pinhole is used.

Produce a magnified image (magnification 2.5 to 3 times) of the pinhole.

The dimensions of the focal spot are derived by examining the images through the magnifying glass

and correcting for the magnification factor according to f=F/Mpinh0|e, where F is the size of the imaged

focal spot. The magnification factor (Mpjnh0ie) is determined by measuring the distance from the pinhole

to the plane of the film (dpinhote.to.fi|m) and the distance from the focal spot to the plane of the pinhole (dfoca,

spot-to-pinhoie)- Mpinhole is ca lcu lated by:

'^'pinhole-^pinhole-to-film ' Sfocai spot-to-pinhole (2-4)

Remark: The method requires a higher exposure than the star pattern method.

Limiting value None.


Equipment Pinhole (diameter 30 pm) with appropriate test stand and magnifying glass (5-1 Ox),

having a built-in graticule with 0.1 mm divisions.

II - D - 6


Source-to-image distance

Measure the distance between the focal spot indication mark on the tube housing and the top surface of the bucky. Add distance between bucky surface and the top of the image receptor.

Limiting value The source-to-image distance should conform to the manufacturers' specification and typically is > 600 mm.

Frequency Only initially. Equipment Tape measure.

Alignment of X-ray field/image receptor

The alignment of the X-ray field and image receptor at the chest wall side can be measured with two loaded cassettes and two X-ray absorbers, e.g. coins. Place one cassette in the bucky tray and the other on top of the breast support table. Make sure the second cassette has a film loaded with the emulsion side away from the screen. It must extend beyond the chest wall side about 30 mm. Mark the chest wall side of the bucky by placing the absorbers on top of the cassette. Automatic exposure will result in sufficient optical densities. Reposition the films on a light box using the imaged absorbers as a reference. The misalignment between film and X-ray field can be measured. Note 1: The lateral edges of the X-ray field should at least expose the ¡mage receptor. A slight extension beyond any edge of the image receptor is acceptable. Note 2: If more than one field size or focal distance is used, the measurement should be repeated for each diaphragm or distance.

Limiting value Thorax-side: X-rays must cover the film by no more than 5 mm outside the film. Lateral sides: X-rays must cover the film to the edges

Frequency Yearly. Equipment X-ray absorbers -e.g. coins, tape measure.

Radiation leakage

The measurement of leakage radiation comprises two parts; firstly the location of leakage and secondly, the measurement of its intensity. Position a beam stopper [e.g. lead sheet) over the end of the diaphragm assembly such that no primary radiation is emitted. Enclose the tubehousing with loaded cassettes and expose to the maximum kilovoltage and a high mAs (several exposures). Process the films and pin-point any excessive leakage. Next, quantify the amount of radiation at the "hot-spots" at a distance of 50 mm of the tube with a suitable detector. Correct the readings to mGy/h (free in air) at the distance of 1 m from the focal spot at the maximum rating of the tube.

Limiting value Not more than 1 mGy in 1 hour at 1 m from the focus at the maximum rating of the tube averaged over an area not exceeding 100 cm2, and according to local regulations.

Frequency Initially and after intervention on the tube housing. Equipment Dose meter and appropriate detector.

Tube output

The specific tube output (pGy/mAs) and the output rate (mGy/s) should both be measured on an axis passing through the reference point, in the absence of scatter material and attenuation (e.g. due to the compression plate). An mAs similar to that required for the reference exposure should be used for the measurement. Correct for the distance from the focal spot to the detector and calculate the specific

I I - D - 7


edition (JUNE 1996)

output at 1 metre and the output rate at a distance equal to the focus-to-film distance (FFD).

Limiting values acceptable: >30 pGy/mAs; desirable: 40-75 pGy/mAs at 1 metre

acceptable: > 7.5 mGy/s; desirable: 10-30 mGy/s at a distance equal to the FFD

Frequency Every six months and when problems occur.

Equipment Dose-meter, exposure timer

Note: A high output is desirable for a number of reasons e.g. it results in shorter exposure times,

minimising the effects of patient movement and ensures adequate penetration of large/dense

breasts within the present back-up time. In addition any marked changes in output require

investigation.

2.1.2 Tube voltage

The radiation quality of the emitted X-ray spectrum is determined by tube voltage, anode material and

filtration. Tube voltage and Half Value Layer (i.e. beam quality assessment) can be assessed by the

measurements described below.

Reproducibility and accuracy

A tube voltage check over the whole used kV-range at 1 kV intervals should be performed. The

reproducibility is measured by repeated exposures at one fixed tube voltage that is normally used

clinically (e.g. 28 kV). A digital kVp-meter (specially designed for mammography) is presently the most

suitable for this purpose.

Note: consult the manufacturers' instruction manual for the correct positioning.

Limiting value Accuracy for 25-31 kV: < ± 1 kV, reproducibility <±0.5 kV.

Frequency Every six months.

Equipment Digital kVp-meter

Half Value Layer

The Half Value Layer (HVL) can be assessed by adding thin aluminium (Al) filters to the X-ray beam

and measuring the attenuation.

Position the exposure detector at the reference point (since the HVL is position dependent) on top of

the bucky. Place the compression device halfway between focal spot and detector. Select 28 kV tube

voltage and an adequate focal spot charge (mAs-setting), and expose the detector directly. The filters

can be positioned on the compression device and must intercept the whole radiation field. Use the

same mAs setting and expose the detector through each filter. For higher accuracy (about 2%) a

diaphragm, positioned on the compression paddle, limiting the exposure to the area of the detector may

be used (see the protocol on dosimetry).

The HVL is calculated by applying formula 2.5.

X^InC—1)-X2x|n(—1)

HVL - TçL_ h_ (2 5)

Γ1

The direct exposure reading is denoted as Y0; Y, and Y2 are the exposure readings with added

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aluminium thicknesses of X, and X2 respectively.

Note 1: The purity of the aluminium a 99.0% is required. The thicknesses of the aluminium sheets should be measured with an accuracy of 1%.

Note 2: For this measurement the output of the X-ray machine needs to be stable. Note 3: The HVL for other (clinical) energies and other target materials and filters may also be

measured for assessment of the mean glandular dose (see appendix 1 and the protocol on dosimetry).

Note 4: Alternatively a digital HVL-meter can be used, but correct these readings under extra filtration following to the manufacturers' manual.

Limiting value For 28 kV Mo/Mo the HVL must be over 0.30 mm Al equivalent. Typically readings are< 0.40 mm Al. For typical readings for other kV's, targets and filters, see appendix 3.

Frequency Yearly. Equipment Dosemeter, aluminium sheets 0.30 and 0.40 mm.

2.1.3 AEC-system

The performance of the Automatic Exposure Control (AEC) system can be described by the reproducibility and accuracy of the automatic optical density control under varying conditions, like different object thicknesses and tube voltages. An essential prerequisite for these measurements is a stable operating film-processor and the use of the reference cassette.

Optical density control setting: central value and difference per step

To compensate for the long term variations in mean density due to system variations the central optical density setting and the difference per step of the selector are assessed. To verify the adjustment of the optical density control, produce exposures with a 45 mm PMMA phantom with varying positions of the optical density control selector. A target value for the mean optical density should be established according to local preference. Once the target is agreed, any deviations must be monitored.

Limiting value The optical density (base and fog included) at the reference point should remain within ±0.15 OD to the target value. Target value is typical in the range: 1.3- 1.8 OD, base and fog included. The desirable quantity for the smallest optical density control step-size is 0.10 OD; <. 0.20 OD per step is acceptable. Adjustable range > 1.0 OD.

Frequency Stepsize: every six months Central density or mAs-value: daily

Equipment PMMA 45 mm thick block, densitometer

Guard timer

The AEC system should also be equipped with a guard timer which will terminate the exposure in case of malfunctioning of the AEC system. Measure the mAs at which the system terminates the exposure.

W a r n i n g : since an incorrect functioning of the guard timer could seriously damage the tube, this measurement should be performed under the responsibility of the manufacturer.

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Short term reproducibility

position the dosemeter in the x-ray beam but without covering the AEC-detector. The short term reproducibility of the AEC system is calculated by the deviation of the exposure meter reading often routine exposures (45 mm PMMA).

Limiting value The deviation of the mean value of exposures must be < ± 5%, desirable would be < ±2%.

Frequency Every six months. Equipment PMMA 45 mm thick block, dosemeter.

Note: For the assessment of the reproducibility, also compare the results from the short term reproducibility with those from the thickness and tube voltage compensation and the optical density control setting at 45 mm PMMA and 28 kV. Any problem will be indicated by a mismatch between those figures.

Long term reproducibility

The long term reproducibility can be assessed from the measurement of optical density and mAs resulting from the exposures of a PMMA-block or the QC phantom in the daily quality control. Causes of deviations can be found by comparison of the daily sensitometry data and mAs recordings (see 2.3.2)

Limiting value <±0.20 OD acceptable; < ± 0.15 OD desirable from the target OD. Frequency Daily Equipment PMMA 45 mm thick block or QC phantom, densitometer

Object thickness compensation

Compensation for object thickness is measured by exposures of PMMA plates in the thickness range 20 to 70 mm, using the clinical setting for the AEC.

Limiting value All optical density variations must be within the range ± 0.15 OD, with respect to the target optical density. Desirable: ±0.10 OD.

Frequency Weekly. Equipment PMMA: plates 10x180x240 mm3, densitometer.

Tube voltage compensation

Compensation for tube voltage is measured over the clinical range of kV, filters and target materials used.

Limiting value All optical density variations must be within the range ±0.15 OD, with respect to the target optical density. Desirable: ±0.10 OD.

Frequency Every six months. Equipment PMMA 45mm, densitometer.

2.1.4 Compression

The compression of the breast tissue should be firm but tolerable. There is no optimal value known for the force, but attention should be given to the applied compression and the accuracy of the indication.

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Compression force

The compression force can be adequately measured with a compression force test device or a bathroom scale (use compressible material e.g. a tennisball to protect the bucky and compression device). When compression force is indicated on the console, it should be verified whether the figure corresponds with the measured value.

Limiting value Maximum automatically applied force: 130 - 200 N. (~ 13-20 kg) Frequency Yearly. Equipment Compression force test device.

Compression plate alignment

The alignment of the compression device at maximum force can be visualized and measured when a piece of foam-rubber is compressed. Measure the distance between bucky surface and compression device on each corner. Ideally, those four distances should be equal. Misalignment normal to the chest wall side is less disturbing than in the parallel direction. The upright edge of the device must be imaged outside the receptor area and optimally within the chestwall side of the bucky.

Limiting value Minimal misalignment is allowed, < 15 mm is acceptable for asymmetrical load and in the direction towards the nipple, < 5 mm for symmetrical load.

Frequency Annually. Equipment Foam rubber, tape measure.

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2.2 Bucky and image receptor

2.2.1 Anti scatter grid

The anti scatter grid is composed of alternating strips of lead and cotton fibre interspace material mainly and is designed to absorb scattered photons. The grid system is composed of a cassette holder, breast support table and a mechanism for moving the grid, to prevent grid lines on the image.

Grid system factor

The grid system factor can be measured with a dosemeter. Produce two images, one with and one without the grid system. Use manual exposure control to obtain images of about unit optical density. The first ¡mage is made with the cassette in the bucky tray (with grid system) and PMMA on top of the bucky, and the second with the cassette on top of the bucky (without grid system) and PMMA on top of the cassette. The grid system factor is calculated by dividing the exposures, corrected for the inverse square law and optical density differences.

Limiting value Grid system factor s 3. Frequency Initially and when dose or exposure time increases suddenly. Equipment Dosemeter, PMMA 45 mm thick block and densitometer.

Grid imaging

To assess the homogeneity of the grid in case of suspected damage or looking for the origin of artefacts, the grid may be imaged by automatic exposure of the bucky at the lowest position of the AEC-selector, without any added PMMA. This in general gives a good image of the gridlines.

2.2.2 Screen-film

The current image receptor in screen-film mammography consists of a cassette with one intensifying screen in close contact with a single emulsion film. The performance of a stock of cassettes is described by the inter cassette sensitivity variation and screen-film contact.

Inter cassette sensitivity and attenuation variation and optical density range

The relative sensitivity of the screens can be assessed with the reference exposure (chapter 1). Select an AEC setting (should be the normal position) to produce an ¡mage having about the clinically used mean optical density on the processed film. Repeat for each cassette using films from the same box or batch. Make sure the cassettes are identified properly. Measure the exposure (in terms of mGy or mAs) and the corresponding optical densities on each film at the reference point.

Limiting value The exposure, in terms of mGy (or mAs), must be within ±5% for all cassettes. The maximum difference in optical density between all cassettes:¿0.20 OD is acceptable, ¿0.15 OD is desirable.

Frequency Initially (including manual exposures), yearly, and after introducing new screens. Equipment PMMA 45 mm or phantom, dosemeter, densitometer.

Screen-film contact

Clean the inside of the cassette and the screen. Wait for at least 5 minutes to allow air between the screen and film to escape. Place the mammography contact test device (mesh: about 40 wires/inch,

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1.5 wires/mm) on top of the cassette and expose to produce a film optical density of about 2 OD at the reference point. Regions of poor contact will be blurred and appear as dark spots in the image. Reject cassettes only when they repeatedly show the same spots.

Limiting value No significant areas of poor contact are allowed in the diagnostically relevant part of the film.

Frequency Initially, yearly and after introducing new screens. Equipment Mammography screen-film contact test device and densitometer.

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2.3 Film processing

2.3.1 Base line performance processor

The performance of the processor greatly affects image quality. The best way to measure its performance is by sensitometry. Measurements like temperature and processing time are performed to establish a base-line performance. No limiting values are given, since temperature and processing time are set to adapt to the requirements of the sensitometry.

Temperature

To establish a base-line performance of the automatic processor, the temperature of developer and fixer are measured. Take care that the temperature is measured at a fixed point, as recommended by the manufacturers. The measured values can be used as background information when malfunction is suspected.

Limiting value None. Frequency Initially and when problems occur. Equipment Thermometer (digital or alcohol, no mercury allowed)

Processing time

The total processing time can be measured with a stopwatch. Insert the film into the processor and start the timer when the signal is given by the processor. When the processed film is available, stop the timer. When malfunction of the processor is suspected, measure this processing time exactly the same way again and check to see if there is any difference.

Limiting value None. Frequency Initially and when problems occur. Equipment Stopwatch.

2.3.2 Film and processor

The films used in mammography should be specially designed for that purpose and should comply with the given figures under "Limiting value". Light sensitometry is a suitable method to measure the performance. Disturbing processor artifacts should be absent on the processed image.

Sensitometry

Use a sensitometer to expose a film with light and insert the exposed side into the processor first. Before measuring the optical densities of the step-wedge, a visual comparison can be made with a reference strip to rule out a procedure fault, like exposure with a different colour of light or exposure of the base instead of the emulsion side. From the characteristic curve (the graph of measured optical density against the exposure by light) the values of base and fog, maximum density, speed and mean gradient can be derived. These parameters characterize the processing performance. A detailed description of these ANSI-parameters can be found in appendix 1, calculation of film parameters.

Limiting value The required values for these parameters are: base and fog: <. 0.20 OD contrast: MGrad: 2.8-3.2

Frequency Daily.

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Equipment Sensitometer, densitometer.

Note: There is no clear evidence for the optimal value of MGrad; the range is based on theory and current experience. A higher value of MGrad might lead to under- and over exposure of parts of the image and therefore reduce the information content. Only in stable conditions with very low variability of the parameters could it further improve image quality.

Daily performance

The daily performance of the processor is assessed by sensitometry. After the processor has been used for about one hour each morning, perform the sensitometry as described above. The variability of the parameters can be calculated over a period of time e.g. one month (see calculation of film parameters in appendix 1).

Limiting value Variability for all parameters acceptable: < ±10%, desirable < ±5%. Frequency Daily and more often when problems occur. Equipment Sensitometer, densitometer.

Note: A more practical approach to the assessment of variations can be found in the use of the following table, where the limiting percentages are expressed as a range of limiting values (Max value - Min value):

base+fog: max. density: speed: mean gradient:

acceptable: <0.03 <0.30 <0.05 <0.20

desirable <0.02 <0.20 <0.03 <0.10

Artifacts

The ¡mage of the PMMA block obtained daily, should be inspected. This should show a homogeneous density, without scratches, shades or other marks indicating artifacts.

Limiting value No artifacts. Frequency Daily. Equipment PMMA block 45 mm or plates 40-60 mm, viewing box

2.3.3 Darkroom

Light tightness of the darkroom should be verified. It is reported, that about half of darkrooms are found to be unacceptable. Cassettes and film hopper should also be light tight. Extra fogging by the safelights must be within given limits.

Light leakage

Remain in the darkroom for a minimum of five minutes with all the lights, including the safelights, turned off. Ensure that adjacent rooms are fully illuminated. Inspect all those areas likely to be a source of light leakage. To measure the extra fog as a result of any light leakage or other light sources, a pre-exposed film of about 1.2 OD is needed. This film can be obtained by a reference exposure of a uniform PMMA block. Always measure the optical density differences in a line perpendicular to the tube axis to avoid influence of the heel effect.

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Open the cassette with pre-exposed film and position the film (emulsion up) on the (appropriate part of the) workbench. Cover half the film and expose for four minutes. Position the cover also perpendicular to the heel effect, to avoid the influence of this inhomogeneity in the measurements. Measure the optical density difference of the background (Dbg) and the fogged area (Dfogged). The extra fog (AD) equals:

AD = D fogged - Db g (2.6)

Limiting value Extra fog: ADs 0.02 OD in 4 minutes. Frequency Initially, every six months and when light leakage is suspected. Equipment Film cover, densitometer.

Safelights

Perform a visual check that all safelights are in good working order (filters not cracked). To measure the extra fog as a result of the safelights, repeat the procedure for light leakage but with the safelights on. Make sure that the safelights were on for more than 5 minutes to avoid start-up effects.

Limiting value Extra fog: ADs 0.10 OD in 4 minutes. Frequency Initially, every six months and every time the darkroom environment has changed. Equipment Film cover, densitometer.

Film hopper

Fogged edges on unexposed (clear) films may indicate that the film hopper is no longer light tight. Place one fresh sheet of film in the hopper. Leave it there for several hours with full white light illumination in the darkroom. Inspect the processed film for light leakage of the hopper.

Limiting value No extra fogging. Frequency This test should be performed initially and when light leakage is suspected.

Cassettes

Dark edges on radiographs indicate a need to perform light leak tests on individual cassettes. Reload the suspect cassette with a fresh sheet of film and place it in front of a viewing box for several hours. Making sure that each side of the cassette is exposed to bright light by turning it over. Inspect the processed film for dark edges due to light leakage of the cassette.

Limiting value No extra fogging. Frequency This test should be performed initially and when light leakage is suspected.

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2.4 Viewing conditions

Since good viewing conditions are important for the correct interpretation of the diagnostic images, they must be optimised. Although the need for relatively bright light boxes is generally appreciated, the level of ambient lighting is also very important and should be kept low. In addition the film should be masked to minimise stray light.

As regards light levels the procedures for photometric measurements and the values required for optimum mammographie viewing are not well established. However there is general agreement on the parameters that are important. The two main measurements in photometry are luminance and illuminance. The luminance of viewing boxes is the amount of light emitted from a surface measured in candela/m2. Illuminance is the amount of light falling on a surface and is measured in lux (lumen/m2). The illuminance that is of concern here is the light falling on the viewing box, i.e. the ambient light level. (An alternative approach is to measure the light falling on the film readers eye by pointing the light detector at the viewing box from a suitable distance with the viewing box off.) Whether one is measuring luminance or illuminance one requires a detector and a photometric filter. This combination is designed to provide a spectral sensitivity similar to the human eye. The collection geometry and calibration of the instrument is different for luminance and illuminance. To measure luminance a lens or fibre-optic probe is used, whereas a cosine diffuser is fitted when measuring illuminance. Where the only instrument available is an illuminance meter calibrated in lux it is common practice to measure luminance by placing the light detector in contact facing the surface of the viewing box and converting from lux to cd/m2 by dividing by n. This approach makes assumptions about the collection geometry, therefore a correctly calibrated luminance detector is preferred.

There is no clear consensus on what luminance is required for viewing boxes. It is generally thought that viewing boxes for mammography need to be higher than for general radiography. In a review of 20 viewing boxes used in mammographie screening in the UK, luminance averaged 4500 cd/m2 and ranged from 2300 to 6700 cd/m2. In the USA the ACR have recommended a minimum of 3500 cd/m2 for mammography. However some experts have suggested that the viewing box luminance need not be very high provided the ambient light is sufficiently low and that the level of ambient light is the most critical factor. The limiting values suggested here seem a reasonable compromise until clearer evidence is available.

2.4.1. Viewing box

Luminance

Measure the luminance close to the centre of the illuminated area using a luminance meter calibrated in cd/m2. An upper limit is included to minimise glare where films are imperfectly masked.

Limiting value Luminance should be in the range 2000-6000 cd/m2. Frequency Yearly. Equipment Luminance meter.

Homogeneity

The homogeneity of a single viewing box is measured by multiple readings of luminance over the surface of the illuminator, compared with the mean value of readings in the middle of the viewing area. Readings very near the edges (e.g. within 5 cm) of the viewing box should be avoided. Gross mismatch between viewing boxes or between viewing conditions used by the radiologist and those used by the radiographer should be avoided. If a colour mismatch exists, check to see that all lamps are of the

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same brand, type and age. To avoid inhomogeneities as a result of dust, clean the light boxes regularly inside and out.

Limiting value The uniformity of luminance across a single light box is typically within ± 30%. The intensity of different light boxes at one department is suggested to be within 15% (measured in the middle of the viewing area).

Frequency Yearly.

Equipment Luminance meter.

2.4.2. Ambient light

Level When measuring the ambient light level (illuminance), the viewing box should be switched off. Place the detector against the viewing area and rotate away from the surface to obtain a maximal reading. This value is denoted as the ambient light level.

Limiting value Ambient light level < 50 lux. Frequency Yearly. Equipment Illuminance meter

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2.5 System properties

The quality of any X-ray image is defined by its ability to transfer the information, necessary to make the right diagnosis, from the tissues examined to the radiologist. This information is proffered by X-ray quanta that are not absorbed by the tissues and reach the detector. The differences in absorption by the different tissues make them discernable. The better the differences are defined, the better the information can be visualised, be it by blackening of the processed film or intensities on a monitor of a digital system. A better separation of the imaged tissues can be achieved by a larger difference between the OD's representing those tissues, and/or by a better definition of the differences in absorption.

The first improvement is achieved by manipulating the X-ray spectrum, either by the choice of a lower kV or of appropriate target and filter materials. It increases the difference in mean value of the OD's of the imaged tissues at the film and by that, the contrast between the tissues. The second improvement is achieved by increasing the system dose. Without affecting the mean values it improves the definition of those values by lowering the standard deviation of their distributions and by that, giving less noise in the imaged tissues.

Both ways to improve image quality are at the cost of a higher patient dose either by more absorption due to the lower energies or by more irradiation to compensate for a less sensitive imaging system. The success of a screening programme is dependent on the proper information transfer and therefore on the image quality of the mammogram. Decreasing the dose per image for reasons of radiation protection is only justified when the information content of the image remains sufficient to achieve the aim.

2.5.1 Dosimetry

The measurement of exposure and the calculation of the mean glandular dose in mammography are described in detail in the European Protocol on Dosimetry in Mammography.(see chapter 6, Bibliography) Only the measurement of entrance surface air kerma is described here for convenience.

Entrance surface air kerma

This measurement is performed under reference conditions either with AEC or manual exposure. Produce two exposures of a PMMA block with an optical density under and over 1.0 OD respectively. The corresponding entrance surface dose should be measured as close to the reference point as possible. The value for the entrance surface air kerma at 1.0 OD (base and fog excluded) can be interpolated linearly from these data.

Limiting value ¿10 mGy for 40 mm PMMA, ±12 mGy for 45 mm PMMA, ¿20 mGy for 50 mm PMMA. (Limiting values for other OD's: see appendix 3)

Frequency Yearly. Equipment Dose meter, PMMA block 150x240 mm2, densitometer.

2.5.2 Image Quality

Although the information content of an image may best be defined in terms of just visible contrasts and details, characterised by its contrast-detail curve, the basic conditions for good performance and the constancy of a system can be assessed by some physical measurements.

Spatial resolution

One of the parameters which determine image quality is the system spatial resolution. It can be adequately measured by imaging two resolution lead bar patterns, up to 20 line pairs/mm each. They are placed either between PMMA plates to measure the resolution in the tissue, or on top of

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PMMA plates with a total thickness of 45 mm, to measure worst-case resolution. Image the patterns at the reference point both parallel and perpendicular to the tube axis, and measure these resolutions. Note: The resolution measured at different heights between 25 and 50 mm from the tabletop does not differ much, since geometric blur is largely compensated by magnification for small focal spot sizes. The distance from the chest wall edge is critical, but the position parallel to the thorax side is not critical within ± 5 cm from the reference point. Resolution is generally worse parallel to the tube axis due to the asymmetrical shape of the focal spot.

Limiting value > 12 Ip/mm acceptable, > 15 Ip/mm desirable at the reference point Frequency Weekly. Equipment PMMA plates 150x240 mm, resolution pattern(s) up to 20 Ip/mm, densitometer.

Image contrast

Since image contrast is affected by various parameters (like tube voltage, film contrast etc.) this measurement is an effective method to detect a range of system faults. Make a reference exposure of an aluminium stepwedge and measure the optical density of each step in the stepwedge. Draw a graph of the readings at each step against the stepnumber. The graph gives an impression of the contrast. Since this graph includes the processing conditions, the film curve has to be excluded to find the radiation contrast, see Appendix 2. Remark: The value for image contrast is dependent on the whole imaging chain, therefore no absolute limits are given.

Limiting value 10% to baseline is suggested. Frequency Weekly. Equipment PMMA or aluminium stepwedge, densitometer.

Threshold contrast visibility

This measurement should give an indication of the lowest detectable contrast of "large" objects (diameter > 5 mm). Therefore a selection of low contrast objects have to be embedded in a PMMA phantom to mimic clinical exposures. There should be at least two visible and two non-visible objects. Note, that the result is dependent on the mean OD of the image. Produce a routine exposure and let two or three observers examine the low contrast objects. The number of visible objects is recorded.

Limiting value <1.3% contrast for a 6 mm detail is suggested. Frequency Weekly. Equipment Test object with low contrast details plus PMMA plates, to a thickness of 45 mm,

densitometer.

Exposure time

Long exposure times can give rise to motion unsharpness. Exposure time may be measured by some designs of kVp- and output meters. Otherwise a dedicated exposure timer has to be used. The time for a routine exposure is measured.

Limiting value Acceptable: < 2 sec; desirable: <1.5 sec. Frequency Yearly and when problems occur. Equipment Exposure time meter, PMMA 45x150x240 mm.

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3 Daily and weekly QC tests.

There is a number of items that should be checked daily or weekly. For this purpose, a dedicated QC-phantom or set of test objects must be available. The procedure must facilitate the measurement of some essential physical quantities, and it should be designed to evaluate:

- AEC reproducibility - tube output stability - reference optical density - spatial resolution - ¡mage contrast - threshold contrast visibility - homogeneity, artifacts - sensitometry (speed, contrast, gross fog)

Note: The reproducibility of the AEC system should be tested daily, using a 40 - 50 mm PMMA block phantom. Its constancy of response to thin and to thick compressed breasts should be tested weekly using PMMA plates covering the range 20 - 70 mm thick.

Practical considerations: Ideally the sensitometric stepwedge should be on the same film as the image of the test object, to be able to correct optimally for the processing conditions. To improve the accuracy of the daily measurement, the phantom should be designed in such a way that it can be positioned reproducibly on the bucky. The shape of the phantom does not have to be breast-like. To be able to perform a good homogeneity check, the phantom should at least cover the normally imaged area (150x240 mm) on the image receptor (180x240 mm). For testing the AEC reproducibility, the PMMA phantom may comprise several layers of PMMA, 10-or 20-mm thick. It is important that the correct thicknesses are known, since commercially available plates are neither identical nor correct in thickness.

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4 Definition of terms

Note that the definitions given here may not be universally applicable but do express the meaning of the terms as used in this document.

Accuracy represents unbiased and precise results. It is the closeness of an observed value of a quantity to the true value. Its value is: the percentage of difference between measured value (m) and true value (t) according: (m/t -1) χ 100%

Air kerma: The quotient of dEtrby dm, measured in Gray, where dEtr is the sum of initial kinetic energies of all the charged ionising particles liberated by uncharged ionising particles in a mass of air dm (adapted fromlCRU 1980)

Automatic exposure control (AEC) system: A mode of operation of an X-ray machine by which the tube loading is automatically controlled and terminated when a pre-set radiation exposure to the image receptor is reached. Also the tube potential (kV) may or may not be automatically controlled.

Average glandular dose: Reference term (ICRP 1987) for radiation dose estimation from X-ray mammography i.e. the average absorbed dose in the glandular tissue (excluding skin) in a uniformly compressed breast of, e.g., 50% adipose, 50% glandular tissue composition. The reference breast thickness and composition should be specified.

Baseline value: The value that is used for comparison when no absolute limiting value is present.

Breast compression: The application of pressure to the breast during mammography so as to immobilize the breast and to present a lower and more uniform breast thickness to the X-ray beam.

Compression paddle: An approximately rectangular plate, positioned parallel to and above the breast table of a mammography X-ray machine, which is used to compress the breast.

Deviation (± %): The percentage of difference between measured value (m) and prescribed value (p) according: (m/p -1) χ 100% .

Dmin, Dmax: see appendix 1: "Calculation of film-parameters"

Entrance surface air kerma (ESAK): The air kerma measured free-in-air (without backscatter) at a point in a plane corresponding to the entrance surface of a specified object e.g., a patient's breast or a standard phantom.

Entrance surface dose (ESD): The absorbed dose in air, including the contribution from backscatter, measured at a point on the entrance surface of a specified object e.g., a patient's breast or a standard phantom.

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Grid: A device which is positioned close to the entrance surface of an image receptor to reduce the quantity of scattered radiation reaching the receptor.

Half-value layer (HVL): The thickness of aluminium absorber which attenuates the air kerma of a collimated X-ray beam by half

Heel effect: The non-uniform distribution of air kerma rate in an X-ray beam in a direction parallel to the cathode-anode axis.

Inverse sguare law: The physical law which states that the X-ray beam intensity reduces in inverse proportion to the square of the distance from the point of measurement to the X-ray tube focus.

Image Quality: Information content of the image in terms of just visible contrasts and details.

Laterally centred: Centred on a line perpendicular to the kathode-anode axis, not necessarily in the middle of the image.

Limiting value: A value of a parameter which, if exceeded, indicates that corrective action is required, although the equipment may continue to be used clinically. Limiting values for dose or air kerma are derived differently from reference values, i.e., reference ESD is based on third quartile values derived during surveys whereas limiting values of other parameters are derived from standard good practice.

Mammography: The X-ray examination of the female breast. This may be undertaken for health screening of a population (mammography screening) or to investigate symptoms of breast disease (symptomatic diagnosis).

MGrad: see appendix 1: "Calculation of film-parameters"

Net optical density: Optical density excluding base and fog.

Optical density (OD): The logarithm of the ratio of the intensity of perpendicularly incident light (lo) on a film to the light intensity (I) transmitted by the film: OD=log(lo/l). Optical density differences are always measured in a line perpendicular to the tube axis to avoid influences by the heel-effect.

Patient: Any woman attending a facility for mammography whether for screening or for symptomatic diagnosis.

Patient dose: A generic term for a variety of radiation dose quantities applied to a (group of) patient(s).

Phantom: Test object, often a series of PMMA-plates or a PMMA-block with various embedded measuring devices.

PMMA: The synthetic material polymethylmethacrylate. Trade names include Lucite, Perspex and Plexiglass.

Precision: The variation (usually relative standard deviation) in observed values.

Quality Assurance as defined by the WHO (1982): "All those planned and systematic actions necessary to provide adequate confidence that a structure, system or component will perform satisfactorily in service (ISO 6215-1980). Satisfactory performance in service implies the optimum quality of the entire diagnostic process-i.e., the consistent production of adequate diagnostic information with minimum exposure of both patients and personnel."

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Quality Control as defined by the WHO (1982): "The set of operations (programming, coordinating, carrying out) intended to maintain orto improve [. . . ] (ISO 3534-1977). As applied to a diagnostic procedure, it covers monitoring, evaluation, and maintenance at optimum levels of all characteristics of performance that can be defined, measured, and controlled."

Radiation detector: An instrument indicating the presence and amount of radiation.

Radiation dose: A generic term for a variety of radiation quantities.

Radiation dosemeter: A radiation detector, connected to a measuring and display unit, which has a geometry, size, energy response and sensitivity suitable for measurements of the radiation generated by an X-ray machine.

Radiation output: The air kerma measured free-in-air (without backscatter) per unit of tube loading at a specified distance from the X-ray tube focus and at stated radiographic exposure factors.

Radiation guality: A measure of the penetrating power of an X-ray beam, usually characterised by a statement of the tube potential and the half-value layer (HVL).

Range: The absolute or relative difference of minimum and maximum values of measured quantities.

Reference cassette: The identified cassette that is used for the QC tests.

Reference exposure: The exposure of the phantom to provide an image at the reference optical density.

Reference optical density: The optical density of 1.0 OD, base and fog excluded, measured in the reference point.

Reference phantom: A phantom similar to the standard phantom, but of a specifically stated thickness.

Reference point: A measurement position in the plane occupied by the entrance surface of a 45 mm thick phantom, 60 mm perpendicular to the chest wall edge of the table and centred laterally.

Reference value (for dose): The value of a quantity obtained for patients which may be used as a guide to the acceptability of a result. In the 1996 version of the "European Guidelines on Quality Criteria for Diagnostic Radiographic Images" it is stated that the reference value can be taken as a ceiling from which progress should be pursued to lower dose values in line with the ALARA principle. This objective ¡salso in line with the recommendations of ICRP Publication 60 (1991) that consideration be given to the use of "dose constraints and reference or investigation levels" for application in some common diagnostic procedures.

Reproducibility indicates the reliability of a measuring method or tested equipment. The results under identical conditions should be constant.

Resolution (at high or low contrast) describes the smallest detectable detail at high or low contrast to a given background.

Routine exposure: The exposure of the phantom under the conditions that would normally be used to produce a mammogram. It is used to determine image quality and dose under clinical conditions.

Speed: see appendix 1: "Calculation of film-parameters"

II - D - 24


edition (JUNE 1996)

Standard breast: A model used for calculations of glandular dose consisting of a 40 mm thick central region

comprising a 50% : 50% mixture by weight of adipose tissue and glandular tissue surrounded by a 5

mm thick superficial layer of adipose tissue. The standard breast is semicircular with a radius ¿80 mm

and has a total thickness of 50 mm. (see: Standard phantom)

Standard phantom: A PMMA phantom to represent approximately the average breast (although not an exact

tissue-substitute) so that the X-ray machine operates correctly under automatic exposure control and

the dosemeter readings may be converted into dose to glandular tissue. The thickness is 45 ± 0.5 mm

and the remaining dimensions are either rectangular a 150 mm χ 100 mm or semi-circular with a radius

of Ì 100 mm.

Target OD: The optical density (OD) at the reference point of a routine exposure, choosen by the local staff

as the optimal value, typically in the range 1.3-1.8 OD, base and fog included.

Test object: see phantom

Threshold contrast: The contrast that produces a just visible difference between two optical densities.

Tube-current exposure-time product (mAs): The product of the X-ray tube current (milliampere, mA) and

the radiographic exposure time (second, s)

Tube loading: The tube-current exposure-time product (mAs) that applies during a particular exposure.

Tube potential: The potential difference (kilovolt, kV) applied across the anode and cathode of the X-ray tube

during a radiographic exposure.

Typical value: The value of a parameter that is found in most facilities in comparable measurements. The

statement of such a value is an indication of what to expect, without any limits attached to that.

X-ray spectrum: The distribution of photon energies in an X-ray beam.

II - D - 25

TABLE 1. Radiographic technique parameters frequency of Quality Control, measured and limiting values.

to ON


X-ray source - focal spot size - source-to-image distance - alignment of x- ray field/image receptor - radiation leakage * output * output rate

tube voltage - reproducibility - accuracy (26 - 30 kV) -HVL

AEC * central opt. dens control setting (1) - opt. dens, control step * short term reproducibility * long term reproducibility - object thickness compensation - tube voltage compensation

compression - compression force - compression plate alignment, asymm. - compression plate alignment, symm.


anti scatter grid * grid system factor

screen-film * inter cassette sensitivity variation (mAs) * inter cassette sensitivity variation (OD range) - screen-film contact

freq.

i i

12 i 6 6

6 6 12

6 6 6 6 w 6

12 12 12

i

12 12 12

typical

0.3 ¿600

40-75 10-30

0.3-0.4

1.3-1.8 0.15

130-200

-

acceptable

IEC/NEMA

<5 < 1 >30 >7.5

<±0.5 <± 1.0 >0.3

<±0.15 <0.20

< ± 5 % <±0.20 <±0.15 <±0.15

< 15 <5

<3

< ±5% <0.20

desirable

<5

>40 > 10

<±0.5 <±1.0

system dep.

< ± 0.15 <0.10

< ± 2 % < ± 0.15 <±0.10 <±0.10

< 15 <5

<3

< ±5% <0.15

unit

mm mm

mGy/hr pGy/mAs

mGy/s

kV kV

mm Al

OD OD

mGy OD OD OD

N mm mm

mGy OD

i = initially; d = daily; w = weekly; 6 = every 6 months; 12 = every 12 months * standard measurement conditions (1) total optical density is indicated, base and fog are included. => This table is continued on next page.

TABLE 1, continued. Radiographic technique parameters frequency and limiting values.

2.3 film processing

processor - temperature - processing time

film - sensitometry: base and fog speed contrast

- daily performance - artifacts

darkroom - light leakage (extra fog in 4 minutes) - safelights (extra fog in 4 minutes) - film hopper - cassettes

2.4 viewing conditions

viewing box - brightness - homogeneity - difference

environment - ambient light level

2.5 system properties

reference dose * entrance surface dose; 45 mm phantom image quality * spatial resolution, reference point

* image contrast variation * threshold contrast visibility * exposure time

freq

i i

d d d d d

12 12 i i

12 12 12 12

12 w w w 12

typical

34-36 90

> 0.15

-

-

acceptable

< 0.20(1)

>2.6 < 10%

< +0.02 (2) <+0.10 (2)

2000 - 6000 < ± 30 %

<50

<12 > 12

< 10%

<2

desirable

< 0.20(1)

2.8-3.2 < 5 %

<+0.02 (2) <+0.10 (2)

2000 - 6000 < ± 30 % <± 15%

<50

< 10 > 15

< 10%

< 1.5

unit

°C s

OD

OD OD

cd/m2

cd/m2

cd/m2

lux

mGy Ip/mm

s

I O

i = initially; d = daily; w = weekly; 6 = every 6 months; 12 = every 12 months * standard measurement conditions (1) for standard blue based films only

(2) at net optical density 1.00 OD => End of table 1.

(O co

QC eguipment

sensitometer densitometer dosemeter thermometer kVp-meter for mammographie use exposure time meter light meter phantoms, PMMA compression force test device

aluminum filters (purity 2 99,5%) focal spot test device stopwatch film/screen contact test tool tape measure rubber foam for compression plate alignment (lead sheet)

accuracy

_ ±2% at 1.0 OD

±5% ±0.3 ±2% ±5%

± 10% ±2%

± 10%

reproducibility

±2% ± 1 % ± 1 % ±0.1 ± 1 % ± 1 % ±5%

-±5%

unit

OD OD

mGy °C kV s

klux mm N


6. Bibliography

CEC-Reports

1 Technical an Physical Parameters for Quality Assurance in Medical Diagnostic Radiology; Tolerances, Limiting Values and Appropriate Measuring Methods 1989: British Institute of Radiology; BIR-Report 18, CEC-Report EUR 11620.

2 Optimization of Image Quality and Patient Exposure in Diagnostic Radiology 1989: British Institute of Radiology; BIR-Report 20, CEC-Report EUR 11842.

3 Dosimetry in Diagnostic Radiology Proceedings of a Seminar held in Luxembourg, March 19-21, 1991. 1992: Rad. Prot. Dosimetry vol 43, nr 1-4, CEC-Report EUR 14180.

4 Test Phantoms and Optimization in Diagnostic Radiology and Nuclear Medicine Proceedings of a Discussion Workshop held in Wuertzburg (FRG), June 15-17, 1992 1993: Rad. Prot. Dosimetry vol 49, nr 1-3; CEC-Report EUR 14767.

5 Quality Control and Radiation Protection of the Patient in Diagnostic Radiology and Nuclear Medicine 1995: Rad. Prot. Dosimetry vol 57, nr 1-4, CEC-Report EUR 15257.

6 European Guidelines on Quality Criteria for Diagnostic Radiographic Images 1996: CEC-Report EUR 16260, in press.

Protocols

1 The European Protocol for the Quality Control of the Technical Aspects of Mammography Screening. 1993: CEC-Report EUR 14821

2 European Protocol on Dosimetry in Mammography. 1996: CEC-Report EUR 16263 in press.

3 Protocol acceptance inspection of screening units for breast cancer screening, version 1993. National Expert and Training Centre for Breast Cancer Screening, University Hospital Nijmegen (NL) 1996 (translated in English).

4 LNETI/DPSR: Protocol of quality control in mammography (in English) 1991.

5 ISS: Controllo di Qualità in Mammografia: aspetti technici e clinici. Instituto superiore de sanità (in Italian), 1995: ISTASAN 95/12

6 IPSM: Commissioning and Routine testing of Mammographie X-Ray Systems - second edition The Institute of Physical Sciences in Medicine, York 1994: Report no. 59/2.

I I - D - 2 9


7 American College of Radiology (ACR), Committee on Quality Assurance in Mammography: Mammography quality control. 1994, revised edition

8 American Association of Physicists in Medicine (AAPM): Equipment requirements and quality control for mammography 1990: report No. 29

Publications

1 Chakraborty D.P.: Quantitative versus subjective evaluation of mammography accreditation phantom images. 1995: Med. Phys. 22(2):133-143

2 Wagner A.J.: Quantitative mammography contrast threshold test tool. 1995: Med. Phys. 22(2): 127-132

3 Widmer J.H.: Identifying and correcting processing artifacts. Technical and scientific monograph Health Sciences Division Eastman Kodak Company, Rochester, New York

4 Caldwell C.B.: Evaluation of mammographie image quality: pilot study comparing five methods. 1992: AJR 159:295-301

5 Wu X.: Spectral dependence of glandular tissue dose in screen-film mammography. 1991: Radiology 179:143-148

6 Hendrick R.E.: Standardization of image quality and radiation dose in mammography. 1990: Radiology 174(3):648-654

7 Baines C.J.: Canadian national breast screening study: assessment of technical quality by external review. 1990: AJR 155:743-747

8 Jacobson D.R.: Simple devices for the determination of mammography dose or radiographic exposure. 1994: Z.Med. Phys. 4:91-93

9 Conway B.J.: National survey of mammographie facilities in 1985, 1988 and 1992. 1994: Radiology 191:323-330

10 Farria D.M.: Mammography quality assurance from A to Z. 1994: Radiographics 14: 371-385

11 Sickles E.A.: Latent image fading in screen-film mammography: lack of clinical relevance for batch-processed films. 1995: Radiology 194:389-392

12 Sullivan D.C. : Measurement of force applied during mammography. 1991: Radiology 181:355-357

I I - D - 3 0


13 Russell D.G. : Pressures in a simulated breast subjected to compression forces comparable to those of mammography. 1995: Radiology 194:383-387

14 Faulkner K. : Technical note: perspex blocks for estimation of dose to a standard breast - effect of variation in block thickness. 1995: Br. J. Radiol. 68:194-196

15 Faulkner K.: An investigation into variations in the estimation of mean glandular dose in mammography. 1995: Radiât. Prot. Dosimet. 57:405-407

16 Young K.C. : Mammographie film density and detection of small breast cancers. 1994: Clin. Radiol. 49:461-465

17 Tang S.: Slit camera focal spot measurement errors in mammography. 1995: Med. Phys. 22:1803-1814

18 Hartmann E.: Quality control of radiographic illuminators and associated viewing equipment. Retrieval and viewing conditions. 1989: BIR report 18:135-137

19 Haus A.G.: Technologic improvements in screen-film mammography. 1990: Radiology 174(3):628-637

20 L.K. Wagner, B.R. Archer, F. Cerra; On the measurement of half-value layer in film-screen mammography. 1990: Med. Phys. (17):989-997.

21 J.D. Everson, J.E. Gray: Focal-Spot Measurement: Comparison of Slit, Pinhole, and Star Resolution Pattern Techniques. 1987: Radiology (165):261-264.

22 J. Law: The measurement and routine checking of mammography X-ray tube kV. 1991: Phys.Med.Biol. (36): 1133-1139.

23 J. Law: Measurements of focal spot size in mammography X-ray tubes. 1993: Brit. J. Of Radiology (66):44-50

24 M. Thijssen et al: A definition of image quality: the image quality figure. 1989: Brit. Inst. Radiology, BIR-report 20: 29-34

25 R. L. Tanner: Simple test pattern for mammographie screen-film contact measurement. 1991: Radiology (178):883-884.

Other reports

1 International Electrotechnical Commission (IEC), Geneva, Switzerland: Characteristics of focal spots in diagnostic X-ray tube assemblies for medical use 1982: IEC-Publication 336.

I I - D - 3 1


2 Quality assurance in mammography - quality control of performance and constancy 1990: Series of Nordic Reports on radiation Safety No. 1, Denmark, Finland, Iceland, Norway and Sweden.

3 Société française des physiciens d'hôpital, Nancy: Contrôle de qualité et mesure de dose en mammographie - aspects théoriques et pratiques (in French) 1991.

4 Department Health & Social Security, Supplies Technology Division (DHSS): Guidance notes for health authorities on mammographie equipment requirements for breast cancer screening 1987: STD:87:34

5 Department of Radiodiagnostic Radiology, University of Lund, Sweden: Quality Assurance in Mammography 1989.

6 Sicherung der Bildqualität in röntgendiagnostischen Betrieben - Filmverarbeitung (in German) 1985: DIN 6868 teil 2: Beuth Verlag GmbH, Berlin.

7 American Association of Physicists in Medicine (AAPM): Basic quality control in diagnostic radiology 1978: report No. 4

8 ECRI: Special issue: Mammography Units; 1989: Health Devices:Vol.18:No.1:Plymouth Meeting (PA)

9 ECRI: Double issue: Mammography Units; 1990: Health Devices:Vol.19:No.5-6:Plymouth Meeting (PA)

10 Siemens Medical Systems Inc., New Yersey: Mammography QA - Doc.# 54780/up 1990

11 ANSI: Determination of ISO speed and average gradient. American National Standards Institute (ANSI). 1983: Nr. PH2.50.

12 Sicherung der Bildqualität in röntgendiagnostischen Betrieben - Konstantzprüfung für die Mammographie (in German) 1989: DIN-1:6868 teil 7:Beuth Verlag GmbH, Berlin.

13 Sicherung der Bildqualität in röntgendiagnostischen Betrieben - Abnahmeprüfung an Mammographie-Einrichtungen (in German) 1989: DIN-2:6868 teil 52: Beuth Verlag GmbH, Berlin.

14 ICRP Publication 52, including the Statement from the Como Meeting of the ICRP. 1987: Annals of the ICRP 17 (4), i-v, Pergamon Press, Oxford, UK.

15 ICRP Publication 60, 1990 Recommendations of the ICRP. (Adopted by the Commission in November 1990); 1991: Annals of the ICRP 21 (1-3), Pergamon Press, Oxford, UK.

I I - D - 3 2


Appendix 1: Calculation of film-parameters

The film curve can be characterized by a few parameters. Most important items are contrast, sensitivity and base and fog. There are different methods to calculate the film parameters. Existing normalizations differ so much that the following method is suggested, derived from the Dutch protocol (1991), which is based on the ANSI (1983) norm.

Dmin Base and fog; the optical density of a non exposed film after developing. The minimum optical density can be visualized by fixation only of an unexposed film. The extra fog is a result of developing the (unexposed) emulsion.

MGrad Mean Gradient; the property which expresses the filmcontrast in the diagnostic range. MGrad is calculated as the slope of the line through the points D^Dmin+0.25 OD and D2=Dmin+2.00 OD. Since the film curve is constructed from a limited number of points, D: and D2 must be interpolated. Linear interpolation of the construction points of the film curve will result in sufficient accuracy.

Speed Sensitivity; the property of the film emulsion directly related to the dose. The Speed is calculated as the x-axis cut-off at optical density 1.00+Dmin, also called 'Speedpoint'. The higher the figure Speed, the more dose is needed to obtain the right optical density. Since the film curve is constructed from a limited number of points, the Speed must be interpolated. Linear interpolation will result in sufficient accuracy.

Two other methods are available for the determination of film contrast, both less precise and less reproducible but easier.

Contrast Index 1: The difference in density found between the step nearest to the speedpoint (density 1.0 OD, base and fog excluded) and the one with a 0.6 loglt (factor 4) higher light exposure (normally 4 density steps) (ACR).

Contrast Index 2: The difference in density steps found between the step nearest to the speedpoint and the step nearest to a density at 2.0 OD, base and fog excluded (IPSM, see bibliography).

D-:


Appendix 2: A method to discriminate between processing and exposure variations by correction for the film-curve

The optical density of a film is the result of X-ray exposure and processing. The film is mainly exposed by light emitted by the intensifying screen. The light-emission of the screen is proportional with the incident X-ray exposure. Primary X-rays only contribute up to 5% of the total exposure. The developing process determines the optical density of the exposed area. When an optical density in any given film is measured, the corresponding exposure is unknown. However, the film curve (measured with light-sensitometry) describes the relation between light-exposure and optical density. Any measured optical density can be converted into a relative log(light-exposure) or log(l') by interpolation of the film curve. This figure log(l') is a relative value and strongly depends on the sensitometer used. But still it is a useful value, closely related with the radiation dose applied and is therefore suitable to calculate the mass attenuation coefficient of an arbitrary step wedge.

When the optical density of several images, taken under identical conditions, are measured, there will be a range of optical densities. This can either be the result of a change in exposure or a change in developing conditions. By calculating the relative figure log(l') we are able to distinguish between processor faults and tube malfunctions.

Approximation of X-ray contrast

To assess the X-ray contrast, correct the OD-readings of an Al-stepwedge for the processing conditions by converting the optical densities into a fictional "exposure", log(l'), according the film curve. Now, a graph of the stepwedge number against "exposure" will result in an almost straight line. The slope of this line is a measure for the X-ray contrast.

II - D - 34


Appendix 3: Typical values for other spectra and densities

Other spectra

The techniques used to produce a mammographie image are constantly optimized. New anode materials, in combination with filters of different composition and thicknesses, may be explored to improve image quality orto reduce patient dose. Some of these new techniques are used in mammography screening. The typical values of the HVL of some of these combinations are listed below (IEC ).

Anode and filter materials

Mo + 30 pm Mo

Mo + 25 pm Rh

W + 60pm Mo

W + 50 pm Rh

W + 40pm Pd

Rh + 25 pm Rh

HVL at 25 kVp m m Al

0.28

0.36

0.35

0.48

0.44

0.34

HVL at 28 kVp m m Al

0.32

0.40

0.37

0.51

0.48

0.39

Other densities

The mean optical density of a mammogram affects the dose imparted in the tissue. Applying a different mean OD in the mammogram changes the exposure and the glandular dose. An indication of the changes expected in respect to the reference exposure (28 kV) are listed below as adaptation of the limiting value for the Entrance Surface Air Kerma (ESAK) and standard Average Glandular Dose (sAGD). The film is expected to fulfill the limiting value by having a MGrad of 3.0 (see the European Protocol on Dosimetry in Mammography, 1996).

net film density (OD)

ESAK (mGy)

standard AGD (mGy)

0.8

9.8

1.6

1.0

12.0

2.0

1.2

14.2

2.4

1.4

16.5

2.8

1.6

18.7

3.1

1.8

20.9

3.5

- D - 3 5


Appendix 4: Sample data sheets for QC reporting

QC report based on

The European Protocol for the Quality Control

of the Physical and Technical Aspects of Mammography Screening

Version: June 1996

Date:

Contact:

Institute:

Address:

Telephone:

Conducted by:

I I - D - 3 7

European Guidel ines for QUALITY A S S U R A N C E in Mammography Screening 2nd

edit ion (JUNE 1996)


2.1.1 X-ray source

Focal spot size

Class (large) focal spot: (IEC)

star pattern method

diameter star pattern

spoke angle θ

diameter magnified star image

diameter first MTF zero ± AC axis

diameter first MTF zero / / AC axis

Dstar:

Θ:

^mag

Dblur J-

Dblur / /

. mm o

mm

mm

mm

M D

mag star

D f=H^Äx D blur

star 180 (Mst -1)

slit camera method

width slit _

distance slit-to-film

distance focus-to-slit

width slit image j . AC axis

width slit image / / AC axis

Mslit -

_ p m

dslit -

focus

film

- slit

; f

Ûslit-to-film·

^focus-to-slit-

Fx:

F/l:

F

Mslit

_ mm

mm

mm J.

mm//

pinhole method

diameter pinhole

distance pinhole-to-film

distance focus-to-pinhole

diameter pinhole χ AC axis

diameter pinhole / / AC axis

« Λ pinhole - film

pinhole ' .

focus - pinhole

Focal spot size f± = mm

ill = mm

C^pinhole-to-film-

C^focus-to-pinhole·

F_L:

Fll:

■ ƒ F

""pinhole

pm mm mm

mm χ mm//

Accepte

I I - D - 3 8


Source-to-image distance Nominal value : Measured value :

Focus indication to bucky Bucky to cassette :

Total focus-film distance :

mm mm

mm

mm

Alignment of X-ray field / image receptor Deviation at chest wall side film:

inside/outside image receptor: left middle: right :

mm, in /out mm, in / out mm, in /out

Accepted: yes / no

Deviation at the short edges of film: beam reaches at the left hand side onto the film edge: yes/no beam reaches at the right hand side onto the film edge: yes/no

Accepted: yes/ no

Radiation leakage Description of position of 'hot spots' 1 2 3

detector surface area : mm2

measured: distance from tube: 50 mm and surface area: mm2

nr: 1. 2. 3.

calculated for 1000 mm, 100 cm2:

mGy/hr mGy/hr mGy/hr

Accepted: yes/ no

Tube output focus detector distance: surface air kerma: focal spot charge:

specific tube output at 1 m output rate at FFD

mm mGy mAs

pGy/mAs mGy/s

Accepted: yes / no

D-39


2.1.2 Tube voltage

Reproducibility and accuracy

Preset mAs: Clinically most relevant kV:

Accuracy

Setting 25 26

Measured

Deviation

mAs kV

27 28 29 30 31 kV

kV

kV

Accepted: yes / no

Reproducibility at the clinically most relevant value

Measured value: 1. 5.

Reproducibility (max deviation from the mean ):

kV

kV

Accepted: yes / no Half Value Layer

Measured tube voltage:

Preset mAs value:

Filtration:

Exposure:

Average exposure:

kV

mAs

1.

2.

3.

0.0

Yo

0.30

Yi

0.40

Y2

mm/1

mGy

mGy

mGy

mGy

2V 2Y 0.3 χ ln(—2-) - 0.4 * ln(—1)

HVL Yn

ln(—)

y. mmAI

HVL: Variation exposure at 0 mm Al

mm Al %

Accepted: yes / no

II - D - 40


2.1.3 AEC-system

Optical density control setting: central value and difference per step

Target density value: OD

Density Density incr. Settin g

-3

-2

-1

0

1

9

3

Exposure

mGy

mAs

mAs OD OD

Accepted: yes / no

Density range: OD Accepted: yes / no

Optical density control setting for D = 1.0 -1.2 OD Optical density control setting for target density:

Guard timer Exposure terminates by exposure limit Alarm or error code : Exposure : Delivered mAs value :

yes/no yes/no

mGy mAs

II - D - 41


Short term reproducibility

Optical density control setting:

Exp. # Exposure mAs

1

2

3

4

5

6

7

8

9

10

Variation in mAs: % (= 100 χ (max-min)/mean ) Accepted: yes / no

Long term reproducibility

Object thickness compensation


Thickness Exposure mAs Density

[cm] [mGy] [mAs] [OD]

2.0

3.0

4.0

5.0

6.0

7.0

Variation in optical density: OD Accepted: yes / no

II - D - 42


Tube voltage compensation


Tube volt. Exposure mAs

[kV] [mGy] [mAs]

25

26

27

28

29

30

31

Variation in optical density: OD

Density

[OD]

Accepted: yes / no

2.1.4 Compression

Compression force

Force-indication: Measured compression force: Compression force after 1 min.

N N N

Compression plate alignment

attachment compression plate : in order / out of order

Symmetric load Thickness indication cm

Height of compression plate above the bucky at full compression:

left right Front : Rear :

Difference(f/r)

difference(l/r) cm cm

cm Accepted: yes / no

I I - D - 4 3


Asymmetric load left-right Height of compression plate above the bucky at full compression:

left right Front : Rear :

Difference(f/r)

difference(l/r) cm cm


Asymmetric load front-rear Height of compression plate above the bucky at full compression:

left Front : Rear :

Difference(f/r)

right difference(l/r) cm cm



2.2.1. Anti scatter grid

Grid system factor Bucky exposure

[mGy] Present: Absent: Bucky factor:

deliv.mAs [mAs]

density [OD]

Accepted: yes / no

Grid imaging

Additional grid images made:

# added PMMA description of artefacts

1.

3.

yes/no

yes/no

yes/no

Accepted: yes / no

II - D - 44


2.2.2. Screen-film

Inter cassette sensitivity and attenuation variation and optical density range

AEC setting: _

(Manual mAs: )

Cassette id exposure [mGy]

1 2 3

5 6 7 8 9 10 11 12

Average values: Variation:

deliv.mAs [mAs]

mAs %

density [OD]

density (manual) [OD]

OD OD

Reference cassette :

Screen-film contact Cassette id: Description of artefacts:

2.3 Film processing

2.3.1. Base line performance of the processor

Temperature Point of measurement in bath:

Developer Fixer reference/nominal: thermometer. reference local: console:

Process time Time from processor signal to film available:

OD

OD

Accepted: yes / no

Accepted: yes/ no

- D - 4 5


2.3.2. Film and processor

Sensitometry

Daily performance

Artifacts

2.3.3. Darkroom

Light leakage Fog (after 4 min.) of a pre-exposed film on the workbench: point: 1 2 3 4 5 D(point) D(background): Deviation: Average deviation: OD

OD OD OD

Positions of light sources and leaks in the darkroom:

Safelights

Type of lighting:

Height :

Setting:

Filter condition :

Fog (after 4 min.) of a

point:

D(point)

D(background):

Deviation:

Average deviation:

, direct/indirect

ca. metre above workbench

insufficient/good/not checked

pre-exposed film on the workbench:

1 2 3 4 5

OD

OD

OD

OD

Film hopper Fogging due to lightleakage in film hopper is absent: yes/no

Cassettes The following cassettes show lightleakage: Cassette id: leaking position

Accepted: yes / no

Accepted: yes / no

Accepted: yes/ no

Accepted: yes / no

I I - D - 4 6


2.4 Viewing conditions

2.4.1. Viewing box

Viewing box luminance Reading from the luminance metre (detector at the centre of the image plane) : Cd/m2

Homogeneity Cover the view box pane with mammography films, measure the luminance (remove films first) at all centre positions of these films.

Position Top Bottom

1

Homogeneity: % ( = 100% .(Lmax - Lmin) / L0

Accepted: yes / no

2.4.2. Ambient light level

Reading from the illuminance metre (detector at the image plane, box is off) : Lux Accepted: yes / no

2.5 System properties

2.5.1 Dosimetry

Entrance surface air kerma

exposure [mGy]

deliv.mAs [mAs]

density [OD]

Exposure for D = 1.00 OD+b+s mGy Accepted: yes / no

I I - D - 4 7


2.5.2 Image Quality

Spatial resolution

Position of the centre of the pattern: Hight above the bucky surface: Distance from thorax side of the bucky: Distance from AC axis:

Resolution

image 1

image 2

image 3

image 4

R± AC-axis

_ mm _mm _ mm

R iAC-axis

Accepted: yes / no

Image contrast

image mAs #1 #2

1

2

3

4

5

#3 #4 #5 #6 #7 #8 #9 #10

Graph(s) attached

Threshold contrast visibility

Observer

1

2

3

# objects identified

Accepted: yes / no

Exposure time AEC setting for a routine image: mAs number obtained: exposure time:

mAs s

Accepted: yes / no

I I - D - 4 8


III

ANNEXES


ANNEX 1:

RECOMMENDATIONS OF THE COMMITTEE OF CANCER EXPERTS ON BREAST CANCER SCREENING 6 APRIL 1992

The Committee recommends that the following criteria be respected by any project intending to implement a breast screening programme:

1. Before initiating large-scale campaigns, pilot schemes (town, district) should be undertaken to obtain the necessary experience, with a view to implementation of national screening programmes before the year 2000 taking into account the costs, the benefits and the effects

2. The ideal frequency for mammography should be two to three years.

3. Action in this area should cover a long period, and long-term follow-up over ten years should be ensured.

Support by the national and/or local health authorities should be assured not only in the screening part, but also in the further investigations which are needed for definite diagnosis, and for the treatment, whenever is necessary, which will inevitably be increased in the pilot area during the lifetime of the experiment. Hence the Committee recommends accepting only those projects which will be officially supported by the national and/or regional health authorities.

4. With respect to selection of age groups, the Committee recommends that the age limit should be the one specified in the tenth rule of the European Code, i.e. 50 years of age, since up to now scientific evidence of the public benefits of screening is limited to women aged 50 to 69 years of age.

At present there is no statistical evidence that population screening under the age of 50 will reduce mortality from breast cancer. Mammographie screening under the age of 50 should be discouraged until the results of ongoing controlled trials become available.

5. Special attention should be paid to the organization of the call and recall system and follow-up of women with suspicious radiological lesions. Quality control measurements should be included in the protocol and be implemented.

6. Adequate staff training (radiologists, technicians as well as physicist) is mandatory.

7. With regard to assessment, the regions to be selected should ideally be towns or districts where a cancer register exists. Where this is not the case, the Committee recommends that the pilot project be selected only if there is a commitment to create simultaneously a breast cancer incidence register.

8. Two view mammography is recommended in the first year of a programme while radiological experience is still being gained. Some experts are of the opinion that two view mammography should be performed on all women attending their first (prevalent) round screen in order to maximise the detection of small cancers and minimise the number of women recalled for further investigation.

m


9. The Committee stresses that double reading should be the general rule. Furthermore, the schemes should include a continuous statistical monitoring of the quality (sensitivity and specificity) to limit the number of errors, whether positive or negative.

10. An acceptable figure for malignant : benign biopsy ratio is 1 : 1. It is understood that it may be difficult to achieve this in the first year of a programme. In subsequent years it should be possible to substantially improve on this figure with the use of cytology.

11. Education and information of the public is necessary not only before, but also during the experience.

12. The criteria of the reduction in mortality should also be complemented by criteria relating to effects on the quality of life (stage of diagnosis, conservative treatment instead of mastectomy, numbers of patients recalled and patients treated for preclinical disease, beneficial and detrimental psychosocial effects and dosimetry) when assessing the results of screening campaigns. Special continuous studies on this aspect should be encouraged.

13. The benefits of a screening programme will be optimized by the formation of good teamwork between the staff at expert centres and those in other units involved. The professional team should include a radiologist, surgeon, cyto/histopathologist and oncologist.

14. Either opportunistic screening or organized screening taking place outside the confines of a national programme should be subject to the same standards of quality control as the national programme.

15. It is agreed that cost-efficiency is an integral part of quality assurance. Adequate documentation of any screening programme and its results is essential in evaluating the programme and demonstrating its safety and benefit to the population being screened. The same methodology in documenting such data is recommended for accurate comparison.

m-2


ANNEX 2:

EUREF PROTOCOL

This protocol and its recommendations with relation to the EUREF programme is time limited to the current Action Plan of Europe Against Cancer.

Confidentiality with regard to findings and reports by EUREF and its associate personnel will be respected between the boards of EUREF, the EAC Subcommittee on Cancer Screening and the European Commission.

Status

The Europe against Cancer Subcommittee on Cancer Screening is committed to ensuring that the pilot breast screening projects funded by it achieve sufficient quality and expertise to function as Quality Assurance Reference Centres in their own country. To this end, EUREF is charged with the responsibility of responding to and coordinating a quality assurance training requirement in a given programme. The nature of this response would be to facilitate contacts and training activities between the pilot study concerned and the source of expertise seen most suitable by the EAC Subcommittee on Cancer Screening. EUREF should further monitor the progress of the programme in question to the point where a satisfactory outcome has been achieved.

In such a way EUREF fulfils its intended function as a European Network of Reference Centres for Breast Cancer Screening.

Guidelines for European Training/Reference Centres have already been introduced and agreed by the Subcommittee on Cancer Screening. Such guidelines should be used as a basis upon which to promote or strengthen programmes in their own countries or within the European Network.

Eventually it is hoped that the pilot projects will reach the sufficient standard to act as reference centres for each of the member states, having suitable political backing from the relevant Departments of Health. The support from EUREF for these projects will vary and diminish in time according to their requirements before they become fully established. There may also be some additional activity between EUREF and external purchasers of the specialist knowledge incorporated into the EUREF network but this must be assessed on the basis of future needs and approval by the board of EUREF and the Subcommittee on Cancer Screening.

In summary EUREF have a major responsibility for quality system support to the pilot breast screening projects. These programmes and EUREF are funded by Europe Against Cancer. EUREF is responsible to the EAC Subcommittee on Cancer Screening for carrying out its duties and the primary authority remains with the Subcommittee on Cancer Screening. The activities of the EUREF Programme will be supervised and recommended by the Advisory Board which can be regarded as an associate sub-group of the Subcommittee on Cancer Screening. This Advisory Board will be composed of relevant members of the Subcommittee on Cancer Screening, representatives of the Pilot network and also representatives of the coordinating centre at Nijmegen.

The EUREF programme is physically based in Nijmegen with some professional specialist input from the staff at the Nijmegen training centre. The activities and experts it coordinates will be more widely based throughout Europe. Individual experts and centres providing training will be approved by the Advisory Board.

m-3


Site visits will be performed by members of the EAC Subcommittee on Cancer Screening. These visits will take the form of fact finding missions and status evaluation. They will assess the current state of Quality Assurance within a programme and will make specific recommendations as to structural and organisational needs as well as training requirements. These visits will maintain liaison between the pilot programmes and the Subcommittee on Cancer Screening. Training visits are defined as those visits to a pilot programme made by personnel recommended by the Scientific Committee to provide training in the individual disciplines required.

Visits by pilot programme personnel to recognised training centres or individuals may take two forms. Firstly, a visit to a recognised individual or screening programme in order to gain a general and broad based experience of structure, organisation and methodology within a screening programme. Secondly, a specific secondment to a recognised training centre by individual scientific personnel connected with the pilot programme.

Purposes

1. To act as an advisory body and provide support to the EAC pilot projects by coordinating the necessary training of relevant personnel by recognised reference and training centres or individual experts.

2. To provide the pilot projects with information on necessary technical and professional quality assurance programmes and to support them in implementing these.

3. Support should be given to a wider allocation of training centres.

4. To provide support in epidemiological evaluation of the pilot projects.

5. A pilot screening programme may be considered suitable for accreditation following the recommendation of EUREF and its visiting teams. The form and manner of accreditation should be decided by the member state concerned.

6. Visits by representatives from the Subcommittee on Cancer Screening to the pilot projects will be maintained, at least once every 2 years, to oversee activities, training needs and act as a liaison with the local teams. Written reports on programme status specifying required actions will be provided to the programme concerned and the European Commission.

7. EUREF should encourage coordinated research within the screening programmes.

I l l - 4


ANNEX 3:

Population screening Act ( The Netherlands).

ACT of 29 October 1992 containing rules relating to population screening (Population Screening Act)

We, Beatrix, by the grace of God, Queen of the Netherlands, Princess of Orange-Nassau, etc.

Whereas, we have considered that it is desirable for the purpose of protecting the population to institute a system of authorisation for population screening programmes which may endanger the health of the persons to be examined, and that separate provisions concerning chest radiography to screen for tuberculosis, as laid down in the Tuberculosis Screening Act (Bulletin of Act, Orders and Decrees[Staatsblad] 1951, 288), are no longer required;

On the advice of the Council of State and in consultation with the Dutch Parliament, have approved and decreed the following:

CHAPTER I

Definitions

Article 1 In this Act and in the provisions issued under it, the following definitions shall apply: a) Our Minister: the Minister for Welfare, Health and Cultural Affairs; b) the Health Council: the Health Council referred to in Article 21 of the Health Act (Bulletin of Act, Orders and

Decrees 1956,51); c) population screening: medical examination of persons performed for the purpose of implementing an offer

made to the whole population or a section thereof and aimed at detecting specific diseases or risk indicators for the benefit, or in part for the benefit, of the persons examined.

CHAPTER II

Population screening for which an authorisation is required

Article 2 1. Population screening involving the use of ionising radiation, population screening for cancer and population

screening for serious diseases or disorders which cannot be treated or prevented shall be subject to the safeguards referred to in Article 3.

2. If, on account of the nature of the screening method to be used or on account of the disease or risk indicator to be detected, Our Minister considers that provisions to protect public health are required immediately, he may designate the screening programmes that are to be subject to the safeguards referred to in Article 3.

3. A bill regulating the matters covered by a decree issued under 2 shall be introduced in the Lower House of the Dutch Parliament within 12 months of the entry into force of such a decree. If the bill is withdrawn or rejected by one of the Houses of the Dutch Parliament, the decree shall be immediately revoked.

Article 3 1. It is forbidden to carry out screening programmes as referred to in Article 2(1) or designated under Article 2(2)

without the authorisation of Our Minister.

Ill-5


2. Rules designed to protect the persons to be examined against the risks associated with the screening programmes referred to in Article 2(1) or with the screening programmes designated under Article 2(2) may be laid down in regulations. Such rules may differ according to the various types of screening programme involved.

3. In the case of the screening programmes referred to in Article 2(1 ) and screening programmes designated under Article 2(2) that are partly carried out for medical research purposes, a regulation may be issued laying down rules concerning the manner in which permission is to be given and in which the individuals involved are to be informed about the purpose, nature and consequences of the screening programme and about protection of privacy for the persons to be examined.

4. An authorisation may be granted subject to restrictions or with requirements attached, solely in sofar as is necessary having regard to the nature of the screening programme for which authorisation is granted, the purpose in either case being to protect the persons to be examined against the risks or to ensure adequate benefit from the screening programme in question.

5. In the case of a designation as referred to in Article 2(2), Our Minister may impose rules as referred to in Article 3(2) and (3); these rules, if not revoked earlier, shall lapse 12 months after they enter into force.

Article 4 1. An application for authorisation as referred to in Article 3(1) shall contain a detailed description of: a) the methods of examination to be used; b) the diseases or risk indicators to be detected; c) the population category to be examined; d) the organisation of the screening programme; e) the quality assurance measures to be taken in respect of the screening programme.

2. Rules concerning other information to be submitted with an application may be laid down in regulations. Such rules may differ according to the various types of screening programme involved.

Article 5 Repealed.

Article 6 Our Minister shall consult the Health Council before taking a decision on an application.

Article 7 1. An application shall be rejected if: a) the screening programme is scientifically unsound; b) the screening programme does not conform to statutory provisions governing medical practice; c) the anticipated benefits of the screening programme are outweighed by the attendant risks to the health of the

persons examined.

2. In the case of the screening programmes referred to in Article 3(3), an authorisation may be rejected if such an examination is not required for public health purposes.

3. In the case of population screening for serious diseases or disorders that cannot be treated or prevented, an authorisation shall be issued only in special circumstances.

Article 8 1. The inspectors referred to in Article 10 shall be informed of the decision on the application in sofar as they

exercise authority in the locality concerned.

Ill-6


2. The decision shall also be announced in the Netherlands Government Gazette (Staatscourant).

Article 9 1. An authorisation may be withdrawn only if: a) the information submitted in order to obtain the said authorisation proves to be incorrect or inadequate to the

extent that a different decision on the application would have been taken if the true circumstances had been fully known when the application was assessed;

b) a restriction subject to which the authorisation has been granted is contravened; c) a requirement attached to the authorisation is not complied with; d) a different decision on the application would have been taken if subsequent scientific knowledge concerning

the screening programme for which authorisation has been granted had been known when the application was assessed;

e) a medical research study is added to the screening programme after authorisation has been granted and a different decision on the application would have been taken if this had been known when the application was assessed.

2. In cases where an authorisation may be withdrawn, restrictions or requirements may be added to it or the restrictions or requirements attached to it may be amended instead.

3. Our Minister shall consult the Health Council before giving effect to paragraphs 1 or 2.

CHAPTER III

Further provisions

Article 10 The public health inspectors designated for the purpose by Our Minister and the officials of the Public Health Supervisory Service acting on their instructions shall be responsible for monitoring compliance with the provisions of this Act and those issued pursuant to it.

Article 11 1. The persons referred to in Article 10 shall be authorised to request information and to demand access to

documents and take copies thereof in sofar as such actions can reasonably be deemed necessary for the performance of their duties.

2. All persons shall be obliged to lend the persons referred to in Article 10 any assistance that may reasonably be deemed necessary for the performance of their duties.

Article 12 Repealed.

Article 13 1. Persons contravening a) the provisions of Article 3(1), b) provisions issued pursuant to Article 3(2), (3) or (5), c) a requirement attached to an authorisation pursuant to Article 3(4), d) the provisions of Article 11(2), shall be liable to a class four fine.

2. The punishable actions referred to in (1) constitute offences.

Article 14

I I I - 7


1. Persons who on the date on which this Act or a decree issued under Article 2(2) enters into force are already carrying out a screening programme for which an authorisation is required under Article 3(1) shall not be required to comply with Article 3(1) and the provisions issued under Article 3(2), (3) or (5) for 13 weeks following the above date, provided that an application for the necessary authorisation has been submitted within that period, or for four weeks after the order containing the decision on that application enters into force.

2. If in his judgment immediate steps have to be taken in the interests of public health, Our Minister may stipulate that the time limits set out in paragraph 1 shall not apply to the persons referred to in the said paragraph who are already carrying out a screening programme.

Article 15 Within five years of the entry into force of this Act, Our Minister shall submit a report on its implementation to both Houses of the Dutch Parliament.

Article 16 The Tuberculosis Screening Act (Bulletin of Act, Orders and Decrees 1951, 288) is repealed.

Article 17 This Act shall enter into force on a date to be determined by Royal Decree.

Article 18 This Act may be cited as the Population Screening Act.

We order and command that this Act shall be published in the Bulletin of Act, Orders and Decrees (Staatsblad), and that all ministerial departments, authorities, bodies and officials whom it may concern shall diligently implement it.

Done at The Hague, 29 October 1992

Beatrix

The State Secretary for Welfare, Health and Cultural Affairs H.J. Simons

Published on 1 December 1992

The Minister for Justice E.M.H. Hirsch Ballin

III


DECREE of 1 August 1995 laying down regulations pursuant to Articles 3(3) and 4(2) of the Population Screening Act (Population Screening Decree)

We, Beatrix, by the grace of God, Queen of the Netherlands, Princess of Orange Nassau, etc.

On the recommendation issued by the Minister for Health, Welfare and Sport on 11 April 1995 (PAO/GZ-952378); Taking account of Articles 3(3) and 4(2) of the Population Screening Act; Having obtained the opinion of the Health Council (opinion of 7 September 1994); Having consulted the Council of State (opinion of 27 June 1995, No W13.95.0195); Having seen the more detailed report of the Minister for Health, Welfare and Sport, dated 14 July 1995 (NoPAO/GZ/95-6771);

Have approved and decreed the following:

Article 1 In this Decree "the Act" means "the Population Screening Act".

Article 2 1. The examination of a person as part of a screening programme as referred to in Article 3(3) of the Act may

only be carried out: a) where the person to be examined has come of age and subsection c) does not apply: with the written consent

of the person concerned; b) where the person to be examined is a minor who is at least 12 years old and subsection c) does not apply: with

the written consent of the person concerned together with the written consent of the parents who are effectively responsible for him or of his guardian;

c) where the person to be examined is at least 12 years old and is unable to exercise reasonable judgment in the matter: with the written consent of the parents who are effectively responsible for him or of his guardian, or if he is of age, of his legal representative, spouse or other partner;

d) where the person to be examined has not yet reached the age of 12: with the written consent of the parents who are effectively responsible for him or of his guardian.

2. If the person referred to in paragraph 1(c) and (d) apparently objects to a procedure being performed on him, it shall be deemed that the consent referred to in paragraph 1(c) has not been given.

3. Persons who have given their consent may withdraw it at any time without indicating the reasons. Such a withdrawal shall not entail the payment of any compensation.

Article 3 1. Before any consent is requested, the persons in charge of the screening programme shall ensure that the person

whose consent is required is informed in writing of the following: a) the purpose, type and duration of the examination; b) the risks of the screening programme to the health of the person undergoing the examination; c) the risks to the person who is to be examined arising from discontinuating the screening programme, d) the inconvenience or other adverse effects associated with undergoing the examination.

2. The information referred to in 1 shall be provided in such a way that it may reasonably be assumed that the person concerned has understood its contents. The latter shall be given sufficient time to enable him, on the basis of this information, to reach a carefully considered decision concerning the consent that has been requested.

Ill-9


3. If the person to be examined is not yet 12 years old or is unable to exercise reasonable judgment in the matter, the person carrying out the examination shall ensure that the individual concerned is given information in a manner appropriate to his ability to understand.

Article 4 Without prejudice to the provisions of Article 4(1) of the Act, applications for an authorisation as referred to in Article 3(1) of the Act shall include: a) the dates on which the screening programme will commence and end; b) a detailed description of the purpose of the programme; c) a detailed description of the potentially detrimental effects of the screening programme; d) a description of the type and layout of the areas or rooms where the screening is to take place.

Article 5 1. Where application is made for an authorisation concerning a screening programme in which X-ray equipment

is used and where the use of such equipment requires an authorisation under the Nuclear Energy Act, a copy of the latter authorisation or of the application for such an authorisation shall be submitted.

2. Where application is made for an authorisation concerning a screening programme for a serious disease or disorder which cannot be treated or prevented, the said application shall contain a description of the special circumstances justifying the programme in question.

Article 6 This Decree shall enter into force on a date to be determined by Royal Decree.

Article 7 This Decree may be cited as the Population Screening Decree.

We order and command that this Decree together with the relevant explanatory memorandum shall be published in the Bulletin of Act, Orders and Decrees (Staatsblad).

The Hague, 1 August 1995

Beatrix

The Minister for Public Health, Welfare and Sport E. Borst-Eilers

Published on 5 September 1995

The Minister for Justice W. Sorgdrager

III- 10


ANNEX 4:

COUNCIL OF EUROPE , COMMITTEE OF MINISTERS RECOMMENDATION No. R (94)11

ON SCREENING AS A TOOL OF PREVENTIVE MEDICINE

I I I - 1 1

COUNCIL OF EUROPE COMMITTEE OF MINISTERS

RECOMMENDATION No. R (94) 11

OF THE COMMITTEE OF MINISTERS TO MEMBER STATES

ON SCREENING AS A TOOL OF PREVENTIVE MEDICINE

(Adopted by the Committee of Ministers on 10 October 1994

at the 518th meeting of the Ministers' Deputies)

The Committee of Ministers,

Considering that the aim of the Council of Europe is to achieve a greater unity between its members and that this aim may be pursued, inter alia, by the adoption of common action in the public health field;

Noting that chronic diseases are the major causes of death and a high social and economic burden in developed countries;

Considering that screening for the early detection of some of these diseases could, in principle, provide a method for their control;

Considering that, as yet, there is no absolute proof of the value of screening and early treatment in most diseases;

Considering that few, if any, diseases can at the present time be regarded as fulfilling all the desirable criteria for screening, and that the recommended evaluative procedures are not often carried out in full;

Recognising that the implementation of widespread screening programmes raises major ethical, legal, social, medical, organisational and economic problems which require initial and ongoing evaluation;

Taking into account the provisions of the Europe an Convention on Human Rights and of the European Social Charter;

Bearing in mind the Convention for the protection of individuals with regard to automatic processing of personal data of 28 January 1981, as well as the provisions of Recommendation No. R (81) 1 on regulations for automated medical banks and Recommendation No. R (83) 10 on the protection of personal data used for purposes of scientific research and statistics,

Recommends to governments of member states that they take account in their national health planning regulations and legislation of the conclusions and recommendations set out in the appendix to this recommendation.

I l l -12

Appendix to Recommendation No. R (94) 11

/. Introduction

1.1. For the purposes of this recommendation, screening means applying a test to a defined group of persons in order to identify an early stage, a preliminary stage, a risk factor or a combination of risk factors of a disease. In any case it is a question of detecting phenomena, which can be identified prior to the outbreak of the disease.

1.2. The object of screening as a service is to identify a certain disease or risk factor for a disease before the affected person spontaneously seeks treatment, in order to cure the disease or prevent or delay its progression or onset by (early) intervention.

1.3. The value of existing forms of screening for infectious diseases is fully acknowledged but these established methods are not considered in detail in this recommendation. Emphasis is made on screening for chronic degenerative non-communicable disorders.

1.4. Screening is only one method of controlling disease. It should be viewed in the whole context of reducing the burden of ill health to the individual and the community by, for example, socio-economic, environmental measures, health education and improvement of existing health care and disease prevention systems.

1.5. Environmental factors are recognised as important contributors to disease, but inherited factors may also play an important role. With the advent of new genetic knowledge, an increasing number of genetic diseases and genetic risk factors for disease will be identified and offer the possibility for new screening procedures. As the procedures for genetic screening are not fully established nor fully evaluated, they have not been included in this recommendation.

1.6. The present position is that the implementation of screening in European countries is fragmentary, with few national screening programmes for the total population but many screening schemes restricted to population groups.

1.7. Because there are differences in health needs and health services, as well as in ethical values and in legal norms and rules between countries, the decision to implement a particular screening programme should be taken in cooperation with the medical profession by each country. Nevertheless there are common general principles and problems which are equally relevant to all systems.

1.8. Screening is a tool which is potentially capable of improving the health of the population but it also has adverse effects. Constant care should be taken to ensure that in any screening programme the advantages prevail over the disadvantages.

1.9. The general benefits of screening are often described. It is, however, also important to be aware of the adverse effects which can be:

- stigmatisation and/or discrimination of (non) participants; - social pressure to participate in the screening and undergo the intended treatment/intervention; - psychological distress where there is no cure for the disease or where the treatment and/or intervention is morally

unacceptable to the individual concerned; - exposure to physical and psychological risks with limited health gains; - creation of expectations which probably cannot be fulfilled; - individuals who are positively screened might experience difficulties such as access to insurance, employment, etc.;

- severe side effects of invasive clinical diagnosis of false positives; - delay in diagnosing false negatives ; - unfavourable cost-benefit relationship of a screening programme.

1.10. The various problems which are encountered in the introduction and provision of screening interrelated. Nevertheless, a distinction may be made between those concerned with:

i. ethical and legal issues; ii. selection of diseases (medically) suitable for screening; iii. economic aspects and evaluation of screening ; ¡v. quality assurance; v. organisation of a screening programme ; vi. scientific research.

Ill- 13

2. Ethical and legal values

2.1. Effectiveness is a necessary prerequisite for the screening to be ethical. It should none the less be kept in mind that screening can be effective and still unethical.

2.2. Advantages and disadvantages of screening for the target population and the individual must be well balanced, taking into account social and economic costs, equity as well as individual rights and freedoms.

2.3. Failure to make known information on the positive and negative aspects of the screening is unethical and infringes the autonomy of the individual.

2.4. The decision to participate in a screening programme should, be taken freely. The diagnoses and treatments which may follow the screening should also require a free and separate consent. No pressure should be used to lead somebody to undergo any of these procedures.

2.5. The right to privacy requires that the results of the tests as a general rule are not communicated to those who do not wish to be informed, are collected, stored, and handled confidentially, and adequately protected. It is preferable not to screen individuals who do not wish to be informed of the results of the screening.

2.6. Neonatal screening can only be justified if the intervention is of direct health benefit to the child. Otherwise screening should be postponed until the child can decide for itself.

2.7. No personal data derived from the screening should be communicated to third parties unless the data subject has given consent to it or in accordance with national law.

2.8. When a screening programme is provided as a service and conducted also for research purposes, the decision to make available personal medical data stemming from the screening programme for research purposes should be taken freely, without undue pressure.

The decision not to take part in the research should not in any way prevent the individual from participating in the screening programme.

3. Criteria for selecting diseases suitable for screening

3.1. The disease should be an obvious burden for the individual and/or the community in terms of death, suffering, economic or social costs.

3.2. The natural course of the disease should be well-known and the disease should go through an initial latent stage or be determined by risk factors, which can be detected by appropriate tests. An appropriate test is highly sensitive and specific for the disease as well as being acceptable to the person screened.

3.3. Adequate treatment or other intervention possibilities are indispensable. Adequacy is determined both by proven medical effect and ethical and legal acceptability.

3.4. Screening followed by diagnosis and intervention in an early stage of the disease should provide a better prognosis than intervention after spontaneously sought treatment.

4. Economic aspects

4.1. The increasing financial burden of health care makes it necessary to assess the economic aspects of screening. However these aspects should not be the overriding consideration. In all screening programmes human consideration regarding the value and quality of life, life expectancy as well as respect for individual rights are of prime importance.

4.2. Economic assessments are necessary to enable rational decisions to be made on the priority to be given to alternative ways of using health resources.

4.3. Measurement of the economic aspects of screening is not fully mastered. Early detection and treatment may be less expensive than late treatment. However, available studies relate only to present screening costs and further work is necessary to determine possible cost control in the long term.

4.4. Non systematic screening or spontaneous screening results in high marginal costs. Only systematic screening is able to provide means for controlling cost. Therefore, constant care should be taken to ensure that in any screening programme the allocated resources are used in an optimal way.

5. Quality assurance 5.1. Screening should aim at the highest possible standards of quality from the medical and organisational point of view.

5.2. Because of the expectations that screening creates as well as its adverse effects, screening should meet the highest quality assurance standards in all its aspects.

Il l- 14

5.3. An assessment of the scientific evidence of the effectiveness of screening in the control of a disease should be made by experimental studies before introducing a screening programme as a service. The practical arrangements for a mass screening, which are directly linked to the health structures and systems, should obtain the same effectiveness as that obtained in the randomised trial. 5.4. Having implemented a screening programme, it should be subjected to continuous independent evaluation. Evaluation will facilitate adaptation of the programme, correction of deficiencies noted and verification of achievement of objectives. The adverse effects of the screening programme should not be ignored in the evaluation which should be carried out by independent public health experts.

5.5. If quality assurance standards are not met in the long term it should be possible for the screening programme to be corrected, and, if this is not possible, stopped.

5.6. The programme must evaluate participation, and the percentage of people screened in the target population, the technical quality of testing and the quality of diagnosis and treatment provided as a follow-up for persons with a positive test result.

Severe side effects of false positives should be revealed and evaluated.

5.7. There is a need for more teaching of medical students in epidemiology and its application to measuring the effects of screening. Similarly post-graduate education in this field is also needed to enable practising doctors to understand the principles and evaluation of screening. .

5.8. Provision of screening programmes requires that training in techniques and interpretation of screening tests is included in undergraduate and post-graduate medical teaching programmes.

5.9. A screening programme requires resources in both staff and technical facilities for carrying out the screening tests. In many instances tests can be performed by non medical staff. Provision should be made for initial and further training of the medical and technical staff who will be involved in performing the screening tests and interpreting their results. Technical methods, including automated techniques, are useful in screening for some diseases. Quality of screening methods should be monitored.

6. Organisation

6.1. The organising body of a screening programme should be held responsible throughout the programme. The organisation of a screening programme should comply with what is described in national guidelines and protocols.

6.2. Within the organisational framework the target population should be defined (by age or otherwise) as well as the frequency of screening tests and the general and specific objectives and quality assurance guidelines.

6.3. It must be stressed that screening cannot succeed without co-operation between preventive and curative systems. Organisation must be tailored to the structures of the health system. If appropriate structures in the curative health care system arc lacking, screening should not be implemented until they are developed (pilot programmes, for example). There are various degrees to which screening services may be integrated with curative services or develop as a separate speciality. The advantages and disadvantages of these should be assessed separately in different health care systems.

6.4. Provisions should be made for the financing of the pro me, the cost of organising and evaluating the structure, the cost of testing, the cost of quality assessment and monitoring, and the cost of the follow-up care of those people who screen positively.

6.5. Process and outcome indicators should be constantly evaluated.

6.6. Systematic collection of data is required in screening programmes to serve the needs of the individual and of the health service. To that end, data should be collected on the target population, on persons screened (with dates and the results of the test carried out), and on the results of eventual diagnostic examinations. Access to a morbidity register considerably facilitates evaluation.

6.7. Adequate protection of all data collected by means of a screening programme should be guaranteed.

6.8. Participation of the public in screening programmes is determined by personal factors (for example attitudes, motivation and anxiety) and by situational factors (waiting time and efficient organisation, for example). These can be influenced for instance by health education and by good organisation of the screening procedure,

6.9. In order to ensure optimal participation by the target population, the best possible information should be widely provided and awareness-raising and education programmes should be organised for both the target population and the health professionals.

6.10. Invitations should be accompanied by written information on the purposes and effectiveness of the programme, on the test, on potential advantages and disadvantages, on the voluntary nature of participation and on how data will be protected. An address should be provided for those who require further information.

6.11. Participants should be informed on how, when and where their test results will be available or will be communicated to them.

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6.12. The positive results found at screening should always be confirmed by subsequent diagnostic tests before commencing a treatment/intervention, unless the screening test is a diagnostic test. It is absolutely essential that adequate diagnostic facilities are available to confirm or reject the screening finding as soon as possible. Similarly, treatment facilities must be available and easily accessible to the confirmed cases. The work load placed on the health services by screening can be very large, especially since most screening programmes also lead to incidental pathological findings unrelated to the disease at which the programme is aimed.

6.13. Combining screening for several diseases into a multiple screening procedure may seem to be convenient to the individual and economic to the programme, but such a "package deal" may negatively influence the extent to which most of the criteria for screening including age limit and frequency would be met.

7. Research

7.1. Research into new, more effective, screening tests must be encouraged and the long-term effects of the various methods of treatment and provision for positive subjects studied. Research must be further developed to answer the numerous social, ethical, legal, medical, organisational and economic questions as well as psychological problems raised by screening, on which evidence is incomplete.

7.2. Quality assurance concerning research programmes should be conducted into the effectiveness of the various screening tests, the practical arrangements for screening, the measures to increase participation, the means of improving test efficiency, follow-up to and provisions for those screened positive, an assessment process and all the economic aspects.

7.3. Information gathered during screening should be available for the purpose of scientific research, for the improvement of health services, and for the benefit of future screening, taking into account full respect of autonomy and confidentiality and the protection of personal privacy.

8. General remarks

8.1. It is particularly important that political decision-makers and target groups should be kept informed of the current state of knowledge about the value of screening for particular diseases. Improved communication should be encouraged.

8.2. Governments should promote the research and evaluation necessary for assessing the value of both new and existing programmes. This form of research necessarily means large-scale research which, in some instances, may be designed as international collaborative studies. Scientific evaluation is the only way in which the positive and negative effects of screening can be assessed in order that a rational decision can be taken on whether a screening programme should be implemented and what resources should be allocated.

Quality assurance (as defined by World Health Organization) .

" All those planned and systematic actions necessary to provide adequate confidence that a structure, system or component will perform satisfactorily in service (ISO 6215- 1980). Satisfactory performance in service implies the optimum quality of the entire diagnostic process i.e., the consistent production of adequate diagnostic information with minimum exposure of both patients and personnel."

Quality control (as defined by World Health Organization) :

"The set of operations (programming, co-ordinating, carrying out) intended to maintain or to improve [...] (ISO 3534-1977). As applied to a diagnostic procedure, it covers monitoring, evaluation and maintenance at optimum levels of all characteristics of performance that can be defined, measured, and controlled."

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ANNEX 5:

EUROPEAN PROTOCOL ON DOSIMETRY IN MAMMOGRAPHY (EXECUTIVE SUMMARY OF EUR 16263)

EUROPEAN PROTOCOL ON DOSIMETRY IN MAMMOGRAPHY

J. Zoetelief, M. Fitzgerald2, W. Leitz3, M. Säbel4

TNO Centre for Radiological Protection and Dosimetry P.O. Box 9034 6800 ES Arnhem The Netherlands

The Radiological Protection Centre St. George's Hospital Blackshaw Road London SW17 OQT United Kingdom

Statens Strålskyddinstitut 17116 Stockholm Sweden

Klinik für Frauenheilkunde der Universität Universitätsstrasse 21/23 D 91054 Erlangen Germany

Advisors

D.R. Dance, London, UK M. Gambaccini, Ferrara, I J.T.M. Jansen, Rijswijk, NL C. Maccia, Cachan, F B.M. Moores, Liverpool, UK H. Schibilla, Brussels, EC M.A.O. Thijssen, Nijmegen, NL

December 1995

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EXECUTIVE SUMMARY

Application of the general principles of radiation protection to medical diagnostic radiology implies that each procedure using X rays or radionuclides is justified and optimized. For diagnostic radiology, including mammography, optimization means that the radiation exposure of the patient should be kept as low as possible, but compatible with the image quality necessary for an adequate diagnosis. The purpose of the European Protocol on Dosimetry in Mammography is to provide dosimetric methods which can serve to increase the awareness of the dose variations due to differences in technique and/or equipment and facilitate the comparability of dose values reported according to national protocols. For countries where national guidance and protocols are not yet available the present protocol provides consistent methods of dose measurement and assessment. The present protocol is also intended to supplement the European Protocol for the Quality Control of the Technical Aspects of Mammography Screening.

The present protocol includes several dosimetric approaches reflecting the various reasons why dosimetry is necessary and the different methods given in national and European protocols and working documents:

1.Measurement on patients (Chapter 1, Appendix A1). This covers determination of Entrance surface air kerma (ESAK) for patients employing either thermoluminescent dosemeters (TLDs), issued and read out by a central laboratory, or calibration of tube output with an appropriate dosemeter. 2.Measurements with a standard phantom (Chapter 2, Appendix A2). ESAK is determined for a standard phantom using TLDs from a central laboratory or through the calibration of tube output with an appropriate dosemeter. 3.Determination of average glandular dose (Chapter 3, Appendix A3). Average glandular dose (AGD) is calculated from ESAK using conversion factors as a function of measured half-value layer (HVL). This can be achieved using either the standard phantom or a representative selection of patients.

Although differences between entrance surface dose (ESD) and ESAK are for mammography, in the order of about 10 per cent at maximum, determination of the ESAK is preferred since almost all national protocols include the determination of ESAK. Chapters 1, 2 and 3 on the various methods of dose assessment should be of interest to doctors, radiologists, radiographers and screening managers. For situations where dose measurements cannot be provided locally, the readers are referred to Sections 1.1 and 2.1 for the determination of ESAK for patients and the standard phantom, respectively. When dosimetry is locally accessible, either through special training of staff and/or availability of a physicist, Sections 1.2 and 2.2 are relevant for determination of ESAK for patients or the standard phantom, respectively. The determination of AGD (Chapter 3) enables a more direct assessment of the potential radiation risk. Each type of measurement has its own "stand alone" protocol. The most appropriate method for a specific user can be derived from the flow diagram presented in the section on "Guidance on use of the document". The appendices corresponding to the measurement methods are intended to provide additional information on the dosimetric approaches. Appendix A4 provides a summary of dosimetric methods recommended in national protocols and tables to convert results according to national protocols into values according to the European Protocol. Appendices A5 and A6 are mainly intended for those interested in additional scientific information. The present protocol is directly linked to the European Working Document on Quality Criteria for Diagnostic Radiographic Images and related Trials (Section 1.1), the European Guidelines for Quality Assurance in Mammography Screening including the European Protocol for the Quality Control of the Technical Aspects of Mammography Screening (Section 2.2) and existing national protocols (Appendix A4). For those performing mammography, the present protocol is intended to increase the awareness concerning general radiation protection principles, needs for quality control of dosimetric aspects of mammography and optimization of day-to-day practice.

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FOREWORD

Mammography as a radiological technique for breast cancer detection is receiving particular attention by several programmes and initiatives of the Commission of the European Communities. Special efforts for its optimization are supported by the programmes "Europe against Cancer" and "Regulatory Aspects and Research Actions in Radiation Protection", as well as by "VALUE" which is the specific programme for the dissemination and utilization of scientific and technological research results.

Various actions were taken in the 1990-1994 period: •strategies for optimizing of the functioning of mammography screening centres were developed, giving rise to the definition of reference centres for guidance in quality assurance and quality control; •the concept of quality criteria was set up, dealing with image criteria, image details, parameters of good radiographic techniques, and criteria for radiation dose to the patient, including reference dose values; •trials were carried out in nearly all European countries on the practical application of the quality criteria; •workshops were organized for the discussion of more standardized quality control tools and methods, for specifying the requirements oftest phantoms for mammography and for assessing the perspectives of digitization in mammography.

For the effective implementation of the conclusions of these actions, the "European Guidelines for Quality Assurance in Mammography Screening" were published, including a European Protocol for the Quality Control of the Technical Aspects of Mammography Screening.

During the elaboration of these European Guidelines it became evident that dose measurement is a crucial part and requires special definitions and guidance for a standardized approach. Thus the present protocol specifies some of the most practicable methods and levels of possible accuracy of dose measurements in mammography. It should allow for comparability and evaluation of dose data that will be acquired from now on, whilst increasing at the same time the awareness of the need for periodical quality control and radiation protection measures.

Mrs. S. Blanco Dr. H. Eriskat Dr. C. Gitzinger Dr. J. Sinnaeve Europe against Cancer Radiation Protection VALUE Radiation Protection Research DGV1 DGXI1 DGXIII1 DG XII1

1 Directorates-General involved: DG V: Employment, Industrial Relations and Social Affairs DG XI: Environment, Nuclear Safety and Civil Protection DG XII: Science, Research and Development DG XIII: Telecommunications, Information Market and Exploitation of Research

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INTRODUCTION

The general radiation protection principle of the International Commission on Radiological Protection (ICRP) postulates that all exposures "should be kept as low as reasonably achievable". In the case of medical radiology this implies that each procedure is justified and optimized (ICRP 1977, ICRP 1991). The 1977 recommendations of the ICRP formed the basis of the radiation protection policy of the Commission of the European Communities (CEC) as formulated, e.g., in the Council Directive 84/466/Euratom of 3 September 1984 laying down basic measures for the radiation protection of persons undergoing medical examination or treatment" (CEC 1984). For diagnostic radiology, optimization means that the radiation dose to the patients should be kept as low as possible, but still providing images compatible with the clinical requirements. The CEC Directive states explicitly in Article 3 that "all (radiological) installations in use must be kept under strict surveillance with regard to radiological protection and the quality control of appliances".

According to these principles, an assessment of the dose to the breast constitutes an important part of quality control for mammography, including symptomatic women and those involved in screening programmes. The method of dose evaluation must be carefully defined in order to allow comparisons of radiation exposure and the assessment of carcinogenic risk.

Since the introduction of the molybdenum anode X-ray tube equipped with a molybdenum K-edge filter in 1969 there has been a growing interest in the evaluation and comparison of absorbed doses in mammography. Early dosimetric investigations concerned mainly the determination of entrance surface dose (including backscatter) for (mostly small) samples of patients as well as for breast phantoms. Measurements on patients yielded information about the variation of radiation exposure and its dependence on breast thickness and tissue composition. The use of phantoms facilitated the comparison of different mammographie techniques and studies on the influence of technical aspects on absorbed dose.

At the beginning there was some uncertainty concerning the thickness and chemical composition of a phantom which should represent the average breast, i.e. produce a value of entrance surface dose which was approximately the same as the mean value of an unselected larger sample of patients. Especially in relation to quality control, polymethylmethacrylate (PMMA) phantoms with a thickness ranging from 40 to 50 mm were proposed. As a compromise, in this protocol a 45 mm thick PMMA phantom ("the standard phantom") is assumed to represent approximately the average breast (Chapter 2) with regard to attenuation and scatter properties of the incident ionizing radiation.

When it became evident that mammographie screening could be an effective tool to reduce breast cancer mortality, there was increasing interest in the assessment of radiation risk. It was obvious that entrance surface dose could be used as an indicator of radiation exposure in certain simple comparison cases, but that this quantity was a poor indicator of carcinogenic risk. Presently, it is largely accepted that the average dose to the glandular tissue, most usefully characterizes the risk of carcinogenesis. This dosimetric quantity is recommended e.g. by the International Commission on Radiological Protection (ICRP 1987), the British Institute of Physical Sciences in Medicine (IPSM 1989, IPSM 1994), the Netherlands Commission on Radiation Dosimetry (NCS 1993) and the United States National Council on Radiation Protection and Measurements (NCRP 1986). It is also adopted in this protocol.

Average glandular dose cannot be measured directly, but is generally calculated under certain assumptions (concerning mainly the tissue composition of the breast) from dose quantities determined at the position of the entrance surface of the breast (Chapter 3). In this context entrance surface air kerma (ESAK) free-in-air (i.e. without backscatter) has become the most frequently used quantity. To avoid confusion,

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efforts are made in this protocol to differentiate between ESAK (without backscatter) and entrance surface dose (ESD, including backscatter), both quantities using air as the reference material.

The preceding more historical remarks already demonstrate the need of a harmonizing European protocol on dosimetry in mammography. The following reasons emphasize this necessity:

•A project for the establishment of quality criteria for diagnostic radiographic images was initiated by the CEC in 1987. The main objective of this project was to contribute to a standardization of quality criteria and to the production of comparable radiographs throughout Europe. After an initial trial (Maccia et al 1989) for six common examinations, including mammography, a working document on "Quality Criteria for Diagnostic Radiographic Images" (CEC 1990) was issued and circulated among professional radiology associations. In order to validate and demonstrate the usefulness of this document a second trial was carried out in 1991. A first evaluation of this trial (Maccia et al 1993) shows excessively high doses in a number of cases, thus demonstrating that serious problems exist. When local expertise or resources are lacking, the accessability of dosimetry provided by a central laboratory will be of help to detect unnecessarily high doses and indicate follow-up actions.

•The "European Guidelines for Quality Assurance in Mammography Screening" (CEC 1993) contain as an appendix a "European Protocol for the Quality Control of the Technical Aspects of Mammography Screening". The protocol however does not include detailed information on the determination of the dose to the breast. The "European Protocol on Dosimetry in Mammography" will supplement the quality control protocol and contribute an answer to some of the points raised.

•Mainly in relation to mammographie screening different national protocols exist, which deal in varying extent with the evaluation of absorbed dose as a part of quality assurance; examples are the protocols of Germany (DGMP 1986), France (GIM 1993), the United Kingdom (IPSM 1989, IPSM 1994), the Netherlands (NCS 1993), the Nordic countries (NRPA 1991), Spain (SEFM/SEPR 1993) and Italy (ISS 1995). For these countries a European Protocol can serve to facilitate the comparability of the reported dose values. For other countries the present protocol provides consistent methods of dosimetry.

•Concerning the assessment of doses in diagnostic radiology, the "1990 Recommendations of the ICRP" state that "periodic measurements should be made to check the performance of equipment and to encourage the optimization of protection" (ICRP 1991, para. 272), and that "consideration should be given to the use of dose constraints, or investigation levels, selected by the appropriate professional or regulatory agency" (ICRP 1991, para. S34). The present protocol can help to comply with these recommendations and to establish reference or limiting dose values as a criterion for good mammographie practice.

The present protocol includes several dosimetric approaches reflecting the various reasons why dosimetry is necessary and the different methods given in national and European protocols and working documents: 1. Measurements on patients 2. Measurements with the standard phantom 3. Determination of average glandular dose

To allow facilities where expertise and local resources are lacking, the possibility to obtain an impression of the radiation exposure associated with their mammographie technique, most appropriate methods using dosemeters provided by a central laboratory are presented. Dosemeters from a central laboratory can be applied for a sample of patients (Section 1.1 ) or a phantom (Section 2.1). The dosimetric approach in the case of mammography screening will be the measurement of ESAK with the standard phantom, which is described in Section 2.2. When dosimetric equipment and expertise is not accessible in-house, ESAK for

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the standard phantom can be obtained through dosemeters provided by a central laboratory (Section 2.1). For screening it is desirable to determine the average glandular dose (Chapter 3).

Each type of measurement is presented in a separate section and is self contained. The most appropriate method for a specific user can be derived from the flow diagram presented in the section on "Guidance on use of the document". The three approaches of dose determination are described in Chapters 1 to 3 of this protocol; these chapters should be of interest to doctors, radiologists, radiographers and screening managers. Additional information to these dosimetric methods is given in the Appendices A1 to A4; which are mainly intended for those interested in the scientific background to the chapters (primarily physicists) and to highlight available scientific information and existing problems. Appendices A5 and A6 provide more general background information on technical parameters influencing absorbed dose and on the carcinogenic risk of mammography. The protocol also includes a definition of terms and references to the scientific literature.

Since the techniques of mammographie imaging and the methods of dose evaluation are subject to further improvement, the protocol has to be updated regularly. Those facilities performing mammography, especially in screening programmes, that have not yet established routine dose assessment procedures are strongly encouraged to follow this protocol.

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ANNEX 6:

In December 1994 the European Commission funded a European consensus Conference on the role of General Practitioners in cancer screening in order to clarify some of the issues involved and to seek the opinion of General Practitioners on their role in cancer screening. The following are the conclusions of this conference.

EUROPEAN CONSENSUS ON THE ROLE OF GENERAL PRACTITIONERS IN WOMEN'S CANCER SCREENING

FLORENCE, 2nd - 3rd DECEMBER 1994

At the Second European Conference on the role of GP's in women's cancer screening in Florence, 2nd -3rd December 1994, the following comments were made summarising the recommendations made at The Hague (Satellite Conference of WONCA Congress - June 1993).

Primary Health Care should always be involved from the beginning when organizing Secondary Preventive programmes, which should themselves (where possible) be developed in the context of national preventive programmes, including Primary Prevention.

The general practitioner, as a front-line doctor has a special role in counselling patients on all individual preventive and health issues. Screening for specific diseases should therefore always be considered in the context of comprehensive family medicine (which involves previous knowledge of the patient including physical, psychological and social aspects).

The key role of the GP includes facilitating aspects of patient care. His involvement in setting up screening programmes is however influenced by the different health care systems in various countries which fall broadly into the two groups shown below.

1. General Practitioners function as the point of access to the system (including access to specialist care), and registration of patient at primary care level is required. There are some differences in detail between these systems in different countries including the distribution of tasks for the GP.

2. In this type of system direct access to specialists without referral is possible and there is no formal need for registration with a general practitioner. This will be referred to in this document as "open" system.

An essential element for the organisation of screening programmes is the centralisation of Individual medical data to allow adequate coordination of care and to favour provision of information and counselling whenever needed by the women. Steps should therefore be taken to ensure that all patients' medical data are summarised and stored at primary physician level, so appropriate individual comprehensive personal counselling can be obtained from the general practitioner.

SETTING UP OF SCREENING PROGRAMMES

Screening programmes should be set up in all European countries in accordance with the guidelines of the

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Europe Against Cancer programmes, taking into account all local circumstances. Sufficient financial sources for the setting up (planning phase) as well as the accomplishment of the programme must be available prior to the start in order to ensure that all those in the target group can take part, including the socially deprived; In principle screening should be free of charge. Programmes should involve a Steering Committee truly representative of local General Practitioners and all other professionals involved in the screening process. Within this committee a consensus should first be reached concerning all issues of screening, in accordance with national and international guidelines. If national consensus exists, it should be thoroughly discussed and made applicable to local situations.

This consensus should, In particular relate to following points:

- Target population - Frequency and access - Programme and organisation - Task definition and task distribution (programme, GP's, specialist care, health administration) - Practice organisation and support - Assessment and therapeutic protocols - Follow up - Training and CME of GP and other personnel - Public education - Monitoring and feedback to GP - Quality assurance

In accordance with accepted ethical principles, adequate treatment facilities must be available before implementation of screening programmes

The role of GP can be promoted by: - Involvement of GP representatives in consensus development - Development of both general and practice guidelines - Setting realistic targets at programme and practice level - Setting up networks involving GP - Specific educational programmes (CME) relating to all aspects of screening - Provision of educational material (practice and public) - Clear statements to the public by the profession and health authorities that the GP has a central role In screening in all systems of health care where GP's should Ideally be involved before the screening and always after mammography - Economic incentives (adequate remuneration for technical act and administration) -Always involving GP representatives in the design of the screening programmes from the beginning

AIMS AND TASKS

A number of specific alms, requirements and tasks were identified. The responsibility for these tasks is different according to the healthcare system. An indicative table was set up for Cervical and Breast Screening. (See annexe 1)

As Breast Cancer Screening differs from Cervical Cancer Screening in detection of cancer instead of precancerous lesions, the following differences should be kept In mind: 1. The GP is not performing the screening test. 2. The GP's orientation is towards ensuring participation and providing counselling rather than

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carrying out technical procedures.

It should be noted that nothing In this document Implies that, In particular in open systems, Individual patients should not be referred for mammography or colposcopy.

GENERAL RECOMMENDATIONS FOR CERVICAL AND BREAST CANCER SCREENING

Organised programmes for Breast and Cervical Cancer Screening should be set up in accordance with the "Europe against Cancer" guidelines Such programmes must have a clearly defined systematic population approach (invitation, public health education).

Educational materials (leaflets) should be specifically designed for the programme and be sufficiently accessible potential to participants.

When possible, invitations and reminder letters should be sent and signed by the GP himself and lists of non-attenders should be flagged. Assessment and therapeutic protocols should be available and accepted by consensus between all professionals involved.

A fail safe mechanism to ensure adequate work-up is the responsibility of the programme. When a woman fails to attend, the GP should be Informed. The GP should cooperate with this system.

Task definition and description should help GPs to plan their activity. An acceptable task definition and task distribution should be part of any programme. Task distribution and task definition are essential in relation to practice staffing. Training of paramedical and other assistants of general practice in a practice based prevention approach, are beneficial.

Feed back about practice performance in relation to set principles is essential to permit improvement In the overall process. The Public should be informed about the role in screening defined for primary health care and learn how to use the services provided. Public health education and community involvement is useful in changing the professional attitude towards a more proactive and systematic preventive approach.

Organizational support of practices from programme level Is a definite need. Direct practice support should be further investigated. Where possible, systematic screening should be used but there are circumstances in which an opportunistic approach may be necessary. Opportunistic preventive testing In daily general practice needs further study. Studies should be organized on the best ways of reducing the psychological side effects of screening, including those associated with reporting abnormal findings. Practical training in a pro-active approach to patients seems feasible and Is recommended.

Practical support strategies within programmes should: - Actively use continuous medical education facilities - Involve GP teachers for peer groups - Organize co-ordination between specialists and GPs - Involve the media actively in discussing the role of GPs and creating a preventive environment of - Involve members of the Public in presenting the results of their own experience as a means of promoting

screening - Plan adequate financial sources

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- Stimulate practice automation

- Set realistic targets

Costs and benefits of different approaches should be evaluated to define priorities for local action.

PROPOSAL FOR FURTHER EUROPEAN ACTIONS

Due to the complexity, and the number of problems involved, and the time needed to come to a representative and real European consensus on General Practitioners involvement and support in Cervical and Breast Cancer Screening Programmes, the conference participants request the European Community to support further meetings of a group of delegates from cancer screening projects, general practitioners' associations and health general administrations. Their aim should be and to fine tune and officially adopt the different principles regarding collaboration between General Practice, Screening Programmes and Health Administrations. It is suggested that a small expert group be set up to provide updating and advice about GP involvement in cancer screening projects.

Constant updating of guidelines is required to take account fresh epidemiological and statistical data and other studies (e.g. quality of life Issues, patient satisfaction, counselling experiences) Research into the cost/effectiveness of using General Practitioners (where appropriate) rather than specialists, In screening programmes, is required.

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European Commission

European Guidelines for Quality Assurance in Mammography Screening

(2nd edition, June 1996)

Editors: Dr C. J. M. de Wolf and Dr N. M. Perry

Luxembourg: Office for Officiai Publications of the European Communities

1996 — 208 pp. — 21 χ 29.7 cm

ISBN 92-827-7454-6

Breast cancer is the commonest cause of cancer death among women. Of the women currently affected by breast cancer approximately 75% are aged 50 or over. The number of breast cancer deaths has doubled in absolute terms since 1960, the increase being almost wholly accounted for by the growth in the size of the population and the increasing age of the population.

Population screening for breast cancer is a major public health intervention and experience shows that suitable performance parameters can only be achieved through strict adherence to quality assurance guidelines. Since screening is targeted essentially at asymptomatic women, the narrow balance between benefits and undesirable effects is completely dependent on programme quality. Achievement of the objective, mortality reduction, is inevitably long term. There are, however, important early performance indicators which can predict outcome and which therefore must be accurately documented. High quality data are essential.

The first edition of the European Guidelines for Quality Assurance in Mammography Screening which was published in 1993 received considerable attention. The concept of quality assurance of a medical intervention in a public health context was recognised The Guidelines also gave a new impulse to the European Network of Breast Cancer Screening to strive for higher quality of the pilot projects and initiated international comparison and exchange of knowledge.

Revision of the guidelines has become necessary in the light of the experience gained from the operation of screening programmes in Europe. For this second edition, full guidelines for epidemiology and pathology are included.

The second edition of the European Guidelines for Quality Assurance in Mammography Screening summarizes the current state of knowledge on systematic breast cancer screening. The Guidelines are applicable to all units providing a breast screening service but should also be observed by any mammographie facility involved in the provision of symptomatic breast care.

* * • • _EUR_ • OFFICE FOR OFFICIAL PUBLICATIONS

* O P * OF THE EUROPEAN COMMUNITIES • = = s = = •

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ISBN ΊΕ-&Ε7-?ΗΒΗ-\η

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European Guidelines for Quality Assurance in Mammography Screening

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