IARC Handbooks of Cancer Prevention

Volume 7

Breast Cancer Screening

IARC Handbooks of Cancer Prevention Programme Head: Harri Vainio

Volume 7: Breast Cancer Screening

Editors:

Harri Vainio, M.D., Ph.D. Franca Bianchini, Ph.D

Technical editor: Elisabeth Heseltine, M.Sc.

Bibliographic assistance: Agnes Meneghel Brigitte Kajo

Photographic assistance: Georges Mollon/Pascale Rousson

Layout: Josephine Thévenoux

Printed by: LIPS, Lyon, France

Publisher: lARCPress International Agency for Research on Cancer 150 cours Albert Thomas, 69372 Lyon, France Tel. +33 4 72 73 84 85 Fax. +334727383 19

WORLD HEALTH ORGANIZATION

INTERNATIONAL AGENCY FOR RESEARCH ON CANCER

IARC Handbooks of Cancer Prevention

Volume 7

Breast Cancer Screening

IARCPress

Lyon, 2002

Published by the International Agency for Research on Cancer, 150 cours Albert Thomas, F-69372 Lyon cedex 08, France

© International Agency for Research on Cancer, 2002

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IARC Library Cataloguing in Publication Data

Breast Cancer Screening! IARC Working Group on the Evaluation of Cancer-Preventive Strategies (2002 : Lyon, France)

(IARC handbooks of cancer prevention ; 7)

1. Breast Neoplasms - prevention & control 2. Mass Screening I, IARC Working Group on the Evaluation of Cancer-Preventive Strategies II. Series

ISBN 92 832 30078 (NLM Classification: Wi) ISSN 1027-5622

Printed in France

International Agency For Research On Cancer The International Agency for Research on Cancer (IARC) was established in 1965 by the World Health

Assembly, as an independently financed organization within the framework of the World Health Organization. The headquarters of the Agency are in Lyon, France.

The Agency conducts a programme of research concentrating particularly on the epidemiology of cancer and the study of potential carcinogens in the human environment. Its field studies are supplemented by biological and chemical research carried out in the Agency's laboratories in Lyon and, through collaborative research agree-ments, in national research institutions in many countries. The Agency also conducts a programme for the edu-cation and training of personnel for cancer research.

The publications of the Agency contribute to the dissemination of authoritative information on different aspects of cancer research. Information about IARC publications, and how to order them, is available via the Internet at: http://www.iarc.fr/

This publication represents the views and

opinions of an IARC Working Group on the Evaluation of Cancer-Preventive

Strategies which met in Lyon, France, 5-12 March 2002

Participants and members of the secretariat: First row from left: T. Kuroishi, M. Blettner, F. Bianchini, M. Hakama, P. Dean, B. Armstrong, P. Pisani,

S. Robles, J. Thévenoux. Middle row: E. Suonio, K. Straif, C. Partensky, S. Taplin, E. Heseltine, C. Baines, J. Hall, I. Andersson, G. Welsch, D. Thomas, N. Segnan, A. B. Miller, A. Kricker, H. Sancho-Gamier,

S. Redman, L. NystrOm. Back row: H. Vainio, S. Narod, H. de Koning, A. Ullrich, J. Tyczynski, E. Weiderpass-Vainio, N. Day, L. Irwig. (Participants missing from photo: V. Beral, I. Ellis and R. Blanks)

Note to the Reader

Anyone who is aware of published data that may influence any consideration in these Handbooks is encouraged to make the information available to the Unit of Chemoprevention, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France

Although all efforts are made to prepare the Handbooks as accurately as possible, mistakes may occur. Readers are requested to communicate any errors to the Unit of Chemoprevention, so that corrections can be reported in future volumes.

Acknowledgements

We would like to acknowledge generous support from the Foundation for Promotion of Cancer Research, Japan (2nd Term Comprehensive 10-Year Strategy for Cancer Control), and from the German Federal Ministry for Health.

Contents

List of participants xi

Preface xiii

1. Breast cancer and screening

The world-wide burden of breast cancer ......1

Breast cancer biology, pathology and natural history as related to screening ............. 4 Barriers to understanding of early cancers ...... 5 Benign breast disease ..................... 5 Carcinoma in situ ......................... 6 Invasive carcinoma ........................ 9 Can a patient be 'cured' of breast cancer '2 16 Diagnosis and treatment ................... 16

Screening for breast cancer: Conceptual considerations .........................17 General definitions .......................18 Positive predictive value, specificity and the issue of over-diagnosis ....................20 Cancers detected at screening, interval cancers and distribution of lead time and sojourn time . . . 20 Period screening: Length bias and the unbiased set ...................................20 A more complex view of cancer .............21

Evaluation of screening for breast cancer . . . 22

2. Screening techniques

Screening mammography ................ 25 X-ray equipment ......................... 25 Radiation dose .......................... 28 Quality control .......................... 28 Sensitivity and specificity .................. 28 Host factors that affect sensitivity ............ 32 One versus two views ..................... 33 Double reading .......................... 34

Other and emerging imaging techniques ......34 Digital mammography ....................... 34 Ultrasonography ........................... 36 Magnetic resonance imaging ................. 36 Positron emission tomography ................ 37 Scintimammography ........................ 38 Electrical impedance imaging ................. 38 Other techniques .......................... 38

Clinical breast examination ................. 39 Technique ................................ 39 Training ................................ 41 Maintenance of standards .................... 42 Costs and potential harms ................... 43 Other issues .............................. 43

Breast self-examination .................... 43 Technique ................................ 43 Training ................................ 44 Maintenance of standards .................... 45 Mechanisms for improving breast self-examination . 45 Costs and potential harms ................... 46 Other issues .............................. 46

3. Use of breast cancer screening

Delivery and uptake of screening ............47 Europe ................................48 Americas ................................54 Oceania and Asia ..........................64

Behavioural factors and the longer-term success of screening .............................72 Information and understanding ................72 Psychological consequences of participation in screening ................................74 Encouraging participation in screening ..........74

vii

Table of contents

4. Efficacy of screening

Methodological and analytical issues in assessing efficacy .......................87 Issues in evaluating the efficacy of screening . 87 Use of randomized controlled trials in evaluation of screening ...............................88 Use of cohort (observational) and case—control studies in evaluating screening ...............91

Efficacy of screening by conventional mammography ............................91 Randomized trials .........................91 Cohort and nested case—control studies ........101 Quasi-experimental study ...................102

Efficacy of screening by clinical breast examination .............................102

Efficacy of screening by breast self- examination ............................. 107 Randomized trials ......................... 107 Cohort studies ............................ 108 Case—control studies ....................... 110 Studies of survival ......................... 110 Studies of extent of disease at diagnosis ........ 111

Efficacy of screening women at high risk .....113 Radiation sensitivity .......................115 Tumour factors ...........................115 Family history ............................115 BRCA1 and BRCA2 ....................... 116 Magnetic resonance imaging .................117

5. Effectiveness of screening

Has screening been implemented in accordance with the results of screening trials" ......... 119 Methods of invitation ....................... 119 Screening processes ....................... 119 Age range ............................... 120 Screening interval ........................ 120 Mammography ........................... 120 Clinical breast examination .................. 121 Breast self examination ..................... 121

Indicators for monitoring and evaluating the effectiveness of screening programmes ......121 Origins of indicators of effectiveness of screening . 122 Performance indicators .....................123 Mortality from and screening for breast cancer in different countries .........................129 Alternative measures of effect on mortality ......132 Balance between false-positive and false-negative results ................................133 Conclusion ..............................134

Hazards (risks) of screening ...............135 Occurrence and consequences of false-positive results in mammography ....................135 Overdiagnosis ............................ 144 Reservoir of potentially detectable breast cancer . . 147 Ductal carcinoma in situ ....................148 Early mortality from breast cancer .............150 Risk for breast cancer induced by radiation ......150

6. Cost—effectiveness of population-based breast cancer screening

Cost-effectiveness analysis: What and why? . . 157 Published analyses .......................157 Application of strict rules ....................158

Elements of cost—effectiveness .............158 Effectiveness .............................158 Unfavourable effects .......................159 Costs ................................161 Discounting effects and costs ................162

Modelling for policy decisions ..............163 Policy decisions on age categories to be screened 164 Policy decisions on screening interval ..........164 Policy decisions on high-risk groups ...........165 Policy decisions on recall or referral ...........165

Participation ............................165

Cost—effectiveness in practice ..............165 Quality of life .............................166 Cost ................................168 Cost—effectiveness ........................168

Limitations of cost—effectiveness analysis .. . . 168

Practical limitations ........................168 Gaps in knowledge ........................169 New developments ........................169

7. Summary

Breast cancer and screening ...............171

World-wide burden ........................171 Biology, pathology and natural history ..........171 Conceptual considerations ..................171

Screening techniques ..................... 171

Screening mammography ................... 171

Other and emerging imaging techniques ........ 172

Clinical breast examination .................. 172

Breast self-examination .................... 172

Use of breast cancer screening .............172

Delivery and uptake of screening .............172 Behavioural considerations in screening participation .............................173

Efficacy of screening .....................173 Methodological and analytical issues in assessing efficacy .................................173 Conventional screening mammography ........173 Clinical breast examination ..................174 Breast self-examination ....................174 Women at high-risk ........................174

Effectiveness of population-based screening . . 175

Implementation of population-based screening in accordance with results of screening trials ......175 Indicators of the effectiveness of population-based screening programmes .....................175 Hazards of screening ......................176

Breast cancer and screening

Overall evaluation .......................179 Effect of screening with mammography on mortality from breast cancer ........................ 179

Influence of inter-screening interval on effect of screening by mammography ................ 179

Effect of breast screening by clinical breast examination on mortality from breast cancer . . . . 180

Effect of breast screening by breast self- examination on mortality from breast cancer . . . . 180

Effectiveness in practice of breast cancer screening with mammography ............... 180

Adverse effects of breast screening Cost—effectiveness of a programme of screening with mammography ....................... 181

Implications for public health ................ 181

9. Recommendations

Research recommendations ............... 183

Improving conventional mammography ........ 183

Implementing mammographic screening

programmes ............................ 183

Accuracy of mammographic screening ......... 183

Clinical breast examination ................. 183

Breast self-examination .................... 184

Consequences of diagnosis of breast cancer . . . . 184

Biology of breast tumours in relation to screening 184

New techniques .......................... 185

Women at high risk ....................... 185

Public health recommendations ............186

Information systems .......................186 Implementation of mammographic screening programmes ............................186

References ...............................187

Glossary .................................219

Cost-effectiveness of population-based screening ..............................176 Working Procedures .......................223

8. Evaluation

Evaluation of the efficacy of breast cancer screening ..............................179

Sources of figures .........................229

List of participants

I. Andersson Department of Diagnostic Radiology Malmö University Hospital Malmö Sweden

B. Armstrong (Chairman) Edward Ford Building A27 University of Sydney Sydney NSW 2006 Australia

C. Baines Department of Public Health Sciences University of Toronto Toronto Ontario M5S 1A8 Canada

V. Beral Imperial Cancer Research Fund Cancer Epidemiology Unit University of Oxford Gibson Building Radcliffe Infirmary Oxford 0X2 6HE United Kingdom

R. Blanks Institute of Cancer Research Royal Cancer Hospital Cancer Screening Evaluation Unit Sutton Surrey 5M2 5NG United Kingdom

M. Blettner Department of Epidemiology and Medical Statistics School of Public Health 33501 Bielefeld Germany

N. Day Strangeways Research Laboratory University of Cambridge Cambridge CB1 8RN United Kingdom

R Dean Department of Diagnostic Radiology University of Turku 20521 Turku Finland

N.J. de Koning Department of Public Health Erasmus University Rotterdam 3000 DR Rotterdam Netherlands

I. Ellis Faculty of Medicine and Health Sciences Division of Histopathology Nottingham City Hospital NHS Trust Nottingham NG5 1 PB United Kingdom

S. Fletcher* Harvard Medical School Harvard Pilgrim Health Care Boston Massachusetts 02115 USA

M. Hakama (Vice-Chairman) University of Tampere School of Public Health 33014 Tampere Finland

L. Irwig Screening and Test Evaluation Program (STEP) Department of Public Health and Community Medicine University of Sydney Sydney NSW 2006 Australia

A. Kricker NHMRC National Breast Cancer Centre Kings Cross Sydney NSW Australia

T. Kuroishi Division of Epidemiology & Prevention Aichi Cancer Center Research Institute 464-8681 Nagoya Japan

A.B. Miller Division of Clinical Epidemiology German Cancer Research Center 69120 Heidelberg Germany

*Unable to attend

IARC Handbooks of Cancer Prevention, Volume 7: Breast Cancer Screening

Observer

A. Ullrich WHO Geneva Switzerland

S. Narod H. Sancho-Gamier The Centre for Research in Women's EPIDAURE Health Centre Val d'Aurelle Toronto M5G 1N8 Parc Euromédicine Canada 34298 Montpellier

France C. Nichols* Office of Science Planning and Assessment National Cancer Institute Bethesda Maryland 20892 USA

L. Nyström Department of Public Health and Clinical Medicine Unit of Epidemiology Umei University 901-85 Umeâ Sweden

S. Redman NHMRC National Breast Cancer Centre Kings Cross NSW Australia

S. Robles Pan American Health Organization Regional Office of the World Health Organization HCP/HCN Washington DC 20037 USA

N. Segnan CPO Piemonte Cancer Prevention Centre Unit of Epidemiology 10123 Torino Italy

S. Taplin Group Health Cooperative Center for Health Studies Seattle Washington 98101-1448 USA

D.B. Thomas Fred Hutchinson Cancer Research Center Seattle Washington 98109-1024 USA

H.G. Welch Department of Medicine and Community and Family Medicine Dartmouth Medical School Hanover New Hampshire 03755 USA

Secretariat

F. Bianchini J. Cheney J. Hall E. Heseltine (Lajarthe, 24290 St Léon-sur-Vézère, France) C. Partensky D.M. Parkin P. Pisani A. Sasco K. Straif L. Stayner E. Suonio J. Tyczynski H. Vainio E. Weiderpass-Vainio

Technical assistance

B. Kajo J. Mitchell C. Mogenet J. Thévenoux

* Unable to attend

xu

Preface

Why a Handbook on breast cancer screening? The scientific process of acquiring infor-mation about the efficacy of breast cancer screening was initiated in 1963, when Sam Shapiro and coworkers intro-duced the Health Insurance Plan study (Shapiro etal., 1988a) in New York, USA, the first randomized controlled trial of the effect of mammography and clinical breast examination in reducing mortality from breast cancer. This study opened the era of randomized controlled trials for evaluation of screening techniques. Cancer screening techniques used before that, such as the Papanicolau (Pap) smear, never underwent proper evaluation in randomized trials before their introduction as a means for popula-tion screening.

Randomized controlled trials have been criticized many times as expensive and slow to provide results. The Breast Cancer Detection Demonstration Project (Baker, 1982) in the USA was initiated to provide data on the efficacy of breast cancer screening rapidly, and the first results appeared in 1979, 3 years before publication of the results of the Health Insurance Plan study. Three more studies - in MalmO, Sweden (Andersson et al., 1988), Edinburgh, Scotland (Roberts et al., 1990) and in two Swedish counties (Tabár et al., 1985) - were initiated 13-14 years after the beginning of the Health Insurance Plan study, and another three studies were initiated in 1980-82, in Canada (Miller et al., 1 992a,b) and in Stockholm (Frisell et al.,

1986) and Goteborg, Sweden (Bjurstam etal., 1997). Thus, a number of random-ized controlled trials, initiated in five different countries over a 20-year period, provide the basis for evidence in the field of mammographic screening.

Mammography was first officially introduced in a population-wide, organized screening programme in Iceland and in several districts in Sweden in 1987. The Netherlands and several regions of Canada followed in 1988, and Finland in 1989. In 1988, the American Cancer Society and the Preventive Services Task Force estab-lished policies in favour of screening for breast cancer in the USA (US Preventive Task Force, 1996). In contrast to the poli-cies in other countries, that in the USA emphasized a triple approach, involving breast self-examination, clinical breast examination and mammography. The Europe Against Cancer programme simultaneously initiated a series of pilot screening programmes in several countries in Europe (Commission of the European Communities, 1996) in order to develop expertise in planning and running high-quality population-based screening programmes before their incorporation into national policy. In the early 1990s, national screening programmes were initiated in Australia and the United Kingdom, and these were followed by organized programmes in several states of the USA, in Israel and, later, in France. Germany and

Switzerland were among the last western countries to join the international trend, with plans to introduce national screening at the beginning of the twenty-first century.

Experience in large-scale mammo-graphic screening by the mid-1 990s, and the availability of data on more recent follow-up from the trials, led to discussion about the value of mammographic screening for women under the age of 50. Even on the basis of the same scien-tific evidence, few countries have estab-lished the same breast cancer screening policy. The policies differ with respect to the target age group to be screened, the frequency of screening, the number of mammographic views to be taken and the screening modalities. In Japan, the policy was based on clinical breast examination until recently, when it was decided to add mammography.

In spite of the vast amount of information available from several randomized trials, some doubt has recently been cast on the value of breast cancer screening in reducing mortality from breast cancer (Gotzsche & Olsen, 2000; Olsen & Gotzsche, 2001). In this volume, the relevant published studies are thoroughly reassessed, together with the newest data, either recently published or in press, according to the procedures and guidelines followed in the Handbooks (see pp. 223)