Oral Contraceptives & Breast Cancer

Committee on the Relationship Between Oral Contraceptives and Breast Cancer

Institute of Medicine

Division of Health Promotion and Disease Prevention

NATIONAL ACADEMY PRESS
Washington, D.C.
1991



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page R1
Oral Contraceptives & Breast Cancer Oral Contraceptives & Breast Cancer Committee on the Relationship Between Oral Contraceptives and Breast Cancer Institute of Medicine Division of Health Promotion and Disease Prevention NATIONAL ACADEMY PRESS Washington, D.C. 1991

OCR for page R1
Oral Contraceptives & Breast Cancer NATIONAL ACADEMY PRESS 2101 Constitution Avenue, N.W. Washington, D.C. 20418 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee appointed by the members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in the examination of policy matters pertaining to the health of the public. In this, the Institute acts under both the Academy's 1863 congressional charter responsibility to be an adviser to the federal government and its own initiative in identifying issues of medical care, research, and education. Support for this study was provided by the National Institute of Child Health and Human Development, pursuant to Contract No. N01-HD-9-2925. Library of Congress Cataloging-in-Publication Data Institute of Medicine (U.S.). Committee on the Relationship Between Oral Contraceptives and Breast Cancer. Oral contraceptives and breast cancer / Committee on the Relationship Between Oral Contraceptives and Breast Cancer, Institute of Medicine, Division of Health Promotion and Disease Prevention. p. cm. Includes bibliographical references and index. ISBN 0-309-04493-6 1. Breast—Cancer—Epidemiology—Congresses. 2. Oral contraceptives—Side effects—Congresses. I. Title. [DNLM: 1. Breast Neoplasms—chemically induced. 2. Contraceptives, Oral—adverse effects. 3. Risk Factors. WP 870 I575o] RA645.C3I57 1991 616.99'449071—dc20 DNLM/DLC for Library of Congress 91-19679 CIP Copyright © 1991 by the National Academy of Sciences Printed in the United States of America The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The image adopted as a logotype by the Institute of Medicine is based on a relief carving from Ancient Greece, now held by the Staatlichemuseen in Berlin.

OCR for page R1
Oral Contraceptives & Breast Cancer Committee on the Relationship Between Oral Contraceptives and Breast Cancer * MAUREEN M. HENDERSON (Chair), Professor of Epidemiology and Medicine, University of Washington, and Head, Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle LANETA J. DORFLINGER, Research Division, Office of Population, U.S. Agency for International Development, Washington, D.C. JACK FISHMAN, President, IVAX Corporation, Miami, Florida * HENRY W. FOSTER, JR., Dean, Meharry Medical College, Nashville, Tennessee FRANK E. GUMP, Chief, Breast Service, Columbia-Presbyterian Medical Center, New York, New York * SAMUEL HELLMAN, Dean, Division of Biological Sciences and The Pritzker School of Medicine, University of Chicago, Chicago, Illinois * BARBARA S. HULKA, Kenan Professor and Chair, Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill DONALD R. MATTISON, Dean, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania SUSAN A. R. McKAY, Professor, University of Wyoming School of Nursing, Laramie, Wyoming *   Member, Institute of Medicine.

OCR for page R1
Oral Contraceptives & Breast Cancer * LINCOLN E. MOSES, Professor, Statistics Department, Stanford University, Palo Alto, California JUDY NORSIGIAN, Co-Director, Boston Women's Health Book Collective, Inc., Somerville, Massachusetts MALCOLM POTTS, President, Family Health International, Durham, North Carolina NEENA B. SCHWARTZ, William Deering Professor, Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois HELENE SMITH, Director, Geraldine Brush Cancer Research Institute, San Francisco, California * PAUL D. STOLLEY, Herbert C. Rorer Professor of Medical Sciences, School of Medicine, University of Pennsylvania, Philadelphia VIVIAN PINN-WIGGINS, Chairman, Department of Pathology, Howard University College of Medicine, Washington, D.C. Institute of Medicine Staff GARY B. ELLIS, Study Director and Director, Division of Health Promotion and Disease Prevention ANDREW M. POPE, Senior Staff Officer ROBYN Y. NISHIMI, Senior Staff Officer † LINDA A. DePUGH, Administrative Assistant CYNTHIA ABEL, Financial Associate *   Member, Institute of Medicine. †   Through April 1990.

OCR for page R1
Oral Contraceptives & Breast Cancer Preface The Committee on the Relationship Between Oral Contraceptives and Breast Cancer was assembled in the fall of 1989 by the Division of Health Promotion and Disease Prevention of the Institute of Medicine (IOM) to examine the etiology of breast cancer as it relates to the use of oral contraceptives. The sponsor, the National Institute of Child Health and Human Development, asked the IOM committee to hold a conference to identify and highlight relevant issues, review policy options, offer suggestions for future research, and make recommendations for practicing physicians. The questions addressed by the committee encompass clinical, personal, public health, and research matters. Are current oral contraceptive formulations safe? Will future pills be safer? What is the safest way to use them? Are they perfectly safe for some women but require judicious use by others? Do they increase breast cancer risk in women of all or only some ages? Could their widespread long-term use affect future nationwide breast cancer rates? Are there short-term markers of breast cancer that could be used to abbreviate epidemiological studies linking oral contraceptive use to subsequent clinical diagnoses of breast cancer? If short-term surrogate markers of breast cancer can be developed for this purpose, can they be used to unravel the causes of breast cancer? What must be done at a national level to ensure the safest personal and public health decisions about oral contraceptive use? Although some of these questions yielded to the committee's inquiry, others proved less tractable and will require further research.

OCR for page R1
Oral Contraceptives & Breast Cancer Committee members were drawn from diverse scientific fields. They chose to assess the current state of knowledge of the beneficial or harmful influence of oral contraceptive use on breast cancer, patterns of use and changes in patterns of use, changes in formulations, biology of the breast, breast carcinogenesis, epidemiologic strategies, and animal and human research models and systems. A conference with invited speakers and prepared papers amplified the assessment. Four of the contributed papers, by Kathleen E. Malone, David B. Thomas, Diana B. Petitti, and David C. G. Skegg, are reproduced in this volume. Others are available from the National Technical Information Service. The committee's interpretation and synthesis of the conference and contributed papers led to identification of gaps in current knowledge in many, if not all, of the dimensions noted above. This report recommends ways to begin to seek out information to fill those crucial gaps. In carrying out its task, the committee was ably supported and guided by its IOM staff colleagues. MAUREEN M. HENDERSON, Chair Committee on the Relationship Between Oral Contraceptives and Breast Cancer

OCR for page R1
Oral Contraceptives & Breast Cancer Contents     EXECUTIVE SUMMARY   1      Maintaining Surveillance,   5      Developing a Broader Array of Contraceptives,   5      Assessing Knowledge for Application in Clinical Practice,   6      Filling Gaps in Biological and Epidemiological Knowledge,   7  1   INTRODUCTION AND OVERVIEW   9      Biological Plausibility of a Link Between Oral Contraceptives and Breast Cancer,   12      What Is——and Is Not—Known,   13      Seeking Answers,   18  2   EPIDEMIOLOGY: INFORMATION NEEDS AND DATA GAPS   25      Epidemiological Research,   25      Case-Control Method,   26      Cohort Studies,   27      Comparison Groups,   28      Ecological Studies,   28      Special Studies,   29      Changing Oral Contraceptive Formulations,   33      Summary and Conclusions,   33  3   BIOLOGY: INFORMATION NEEDS AND DATA GAPS   35      Signal Complexity in Breast Regulation,   36      Research Issues,   38      Relationships Among Cell Types,   40      Receptors,   40      Timing,   41      Effects of Pregnancy and Lactation,   41

OCR for page R1
Oral Contraceptives & Breast Cancer      Pathological Breast Tissue,   42      Oncogenes,   44      Molecular Changes Associated with Human Breast Cancer,   45      Research Models,   48      Breast Cancer Cell Lines,   49      Short-term Culture of Normal Mammary Epithelium,   50      Organ Culture,   52      Nude Mouse Model,   53      Summary and Conclusions,   53  4   INFORMATION FOR USERS OF THE PILL AND HEALTH CARE PROVIDERS   55      Benefits and Risks of Oral Contraceptives,   55      Benefits,   55      Risks,   57      Current Controversy,   57      Prescribing Problems,   59  5   POLICY ISSUES AND RECOMMENDATIONS   61      Maintaining Surveillance,   61      Cooperative Research,   63      Surveillance Requirements of the Food and Drug Administration,   63      Developing a Broader Array of Contraceptives,   64      Assessing Knowledge for Application in Clinical Practice,   64      Filling Gaps in Biological and Epidemiological Knowledge,   65     REFERENCES   68     APPENDIXES       A  Oral Contraceptives and Breast Cancer: A Review of the Epidemiological Evidence with an Emphasis on Younger Women (Kathleen E. Malone)   75     B  Oral Contraceptives and Breast Cancer: Review of the Epidemiological Literature (David B. Thomas)   102     C  The Evolving Formulations of Oral Contraceptives   143     D  Animal Models of Sex Steroid Hormones and Mammary Cancer: Lessons for Understanding Studies in Humans (Diana B. Petitti)   152     E  Risks and Benefits of Oral Contraceptives: Will Breast Cancer Tip the Balance? (David C. G. Skegg)   165     F  List of Background Documents   175     INDEX   177

OCR for page R1
Oral Contraceptives & Breast Cancer Oral Contraceptives & Breast Cancer

OCR for page R1
Oral Contraceptives & Breast Cancer This page in the original is blank.