BREAST CANCER
AND THE ENVIRONMENT
A LIFE COURSE APPROACH
Committee on Breast Cancer and the Environment:
The Scientific Evidence, Research Methodology, and Future Directions
Board on Health Care Services
Board on Health Sciences Policy
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
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 study was supported by a contract between the National Academy of Sciences and Susan G. Komen for the Cure®. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.
Library of Congress Cataloging-in-Publication Data
Institute of Medicine (U.S.). Committee on Breast Cancer and the Environment: The Scientific Evidence, Research Methodology, and Future Directions.
Breast cancer and the environment : a life course approach / Committee on Breast Cancer and the Environment: The Scientific Evidence, Research Methodology, and Future Directions, Board on Health Care Services, Board on Health Sciences Policy.
p. ; cm.
Includes bibliographical references.
ISBN 978-0-309-22069-9 (pbk.) — ISBN 978-0-309-22070-5 (PDF)
I. Title.
[DNLM: 1. Breast Neoplasms—etiology. 2. Environmental Exposure—adverse effects. 3. Breast Neoplasms—prevention & control. 4. Risk Factors. WP 870]
362.19699’449—dc23
2012007110
Additional copies of this report are available from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu.
For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu.
Copyright 2012 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
Cover credit: Illustration by Diana Ong/Getty Images.
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 serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.
Suggested citation: IOM (Institute of Medicine). 2012. Breast cancer and the environment: A life course approach. Washington, DC: The National Academies Press.
“Knowing is not enough; we must apply.
Willing is not enough; we must do.“
—Goethe
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
Advising the Nation. Improving Health.
THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering and Medicine
The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is president of the National Academy of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.
COMMITTEE ON BREAST CANCER AND THE
ENVIRONMENT: THE SCIENTIFIC EVIDENCE, RESEARCH
METHODOLOGY, AND FUTURE DIRECTIONS
IRVA HERTZ-PICCIOTTO (Chair), Professor and Chief, Division of Environmental and Occupational Health, University of California, Davis
LUCILE ADAMS-CAMPBELL, Professor of Oncology, Associate Director, Minority Health and Health Disparities Research, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center
PEGGY DEVINE, Founder and President, Cancer Information and Support Network
DAVID EATON, Associate Vice Provost for Research, and Professor and Director, Center for Ecogenetics and Environmental Health, University of Washington
S. KATHARINE HAMMOND, Professor, Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley
KATHY J. HELZLSOUER, Director, The Prevention and Research Center, Mercy Medical Center
ROBERT A. HIATT, Professor and Chair, Department of Epidemiology and Biostatistics, and Director, Population Sciences, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco
CHANITA HUGHES HALBERT, Associate Professor, Department of Psychiatry, University of Pennsylvania, and Director, Center for Community-Based Research and Health Disparities
DAVID J. HUNTER, Dean for Academic Affairs and Vincent L. Gregory Professor in Cancer Prevention, Harvard School of Public Health
BARNETT KRAMER, Editor-in-Chief, Journal of the National Cancer Institute, and Editor-in-Chief, National Cancer Institute Physician Data Query (PDQ) Screening and Prevention Editorial Board
BRYAN M. LANGHOLZ, Professor, Division of Biostatistics, Department of Preventive Medicine, University of Southern California (resigned July 2011)
PEGGY REYNOLDS, Senior Research Scientist, Cancer Prevention Institute of California
JOYCE S. TSUJI, Principal Scientist, Center for Toxicology and Mechanistic Biology, Exponent
CHERYL LYN WALKER, Welch Professor and Director, Institute of Biosciences and Technology, Texas A&M Health Science Center
LAUREN ZEISE, Chief, Reproductive and Cancer Hazard Assessment Branch, Office of Environmental Health Hazard Assessment, California Environmental Protection Agency
Study Staff
LOIS JOELLENBECK, Study Director
JANE DURCH, Senior Program Officer
SHARYL NASS, Senior Program Officer
NIHARIKA SATHE, Research Assistant (from November 2010)
CASSANDRA CACACE, Research Assistant (until December 2010)
ASHLEY McWILLIAMS, Senior Program Assistant (until December 2010)
PATRICK BURKE, Financial Associate
ROGER HERDMAN, Director, Board on Health Care Services
ANDREW POPE, Director, Board on Health Sciences Policy
Commissioned Paper Authors
REBECCA SMITH-BINDMAN, University of California, San Francisco School of Medicine
LINDA DIX-COOPER, University of California, Berkeley
Reviewers
This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report:
Mary Helen Barcellos-Hoff, NYU Langone Medical Center
Julia G. Brody, Silent Spring Institute
Diana Chingos, USC Norris Comprehensive Cancer Center
Kathryn Guyton, U.S. Environmental Protection Agency
Leena Hilakivi-Clarke, Georgetown Lombardi Comprehensive Cancer Center
William A. Knaus, The University of Virginia Health Sciences Center
Ruth M. Parker, Emory University School of Medicine
Lorenz Rhomberg, Gradient
Stephen H. Safe, Texas A&M University
Michael Thun, American Cancer Society
David M. Umbach, National Institute of Environmental Health Sciences, National Institutes of Health
Sandy Walsh, California Breast Cancer Organizations
Noel S. Weiss, University of Washington
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of this report was overseen by David G. Hoel, Medical University of South Carolina, and David A. Savitz, Brown University. Appointed by the National Research Council and the Institute of Medicine, they were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.
Acknowledgments
The committee is grateful for the contribution of participants at its three public meetings. The presentations and discussions at these meetings were valuable in informing the committee about relevant research findings, issues of interest in the research community, the perspectives of advocacy organizations, and the concerns of individuals with breast cancer and their families. The agendas for these meetings appear in Appendix A.
The committee was also ably assisted by Linda Dix-Cooper from the University of California, Berkeley, and Dr. Rebecca Smith-Bindman from the University of California, San Francisco, from whom the committee commissioned papers.
The study was conducted with the generous support of Susan G. Komen for the Cure®. The Institute of Medicine staff worked closely with Dr. Amelie Ramirez, who is a member of the Susan G. Komen for the Cure Scientific Advisory Board and Director of the Institute for Health Promotion Research at the University of Texas Health Science Center at San Antonio. Dr. Ramirez was helpful and supportive as the committee’s point of contact with the Scientific Advisory Board, which originally requested this study. In addition, Kendall Bergman graciously assisted the staff in the administrative coordination with Komen for the Cure.
The committee and project staff appreciate the work of copy editor Laura Penny and gratefully acknowledge valuable assistance within the National Academies from Laura Harbold DeStefano, Greta Gorman, Diedtra Henderson, Jillian Laffrey, William McLeod, Janice Mehler, Abbey Meltzer, Michael Park, Christine Stencel, Vilija Teel, and Lauren Tobias.
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Contents
Study Charge and Committee Activities
Topics Beyond the Scope of the Study
2 BACKGROUND, DEFINITIONS, CONCEPTS
An Introduction to Breast Cancer
Breast Cancer Incidence in the United States
A Broad Perspective on the Environment
Investigating Whether Environmental Factors Are Related to Breast Cancer
3 WHAT WE HAVE LEARNED FROM CURRENT APPROACHES TO STUDYING ENVIRONMENTAL RISK FACTORS
4 CHALLENGES OF STUDYING ENVIRONMENTAL RISK FACTORS FOR BREAST CANCER
Studying Environmental Chemical and Physical Exposures Through Human Studies
Human Epidemiologic Study Design and Implementation
Studying the Role of Genetics in Breast Cancer
Studying Environmental Risk Factors Through Whole Animal and In Vitro Experiments
5 EXAMINING MECHANISMS OF BREAST CANCER OVER THE LIFE COURSE: IMPLICATIONS FOR RISK
Environmental Exposures Over the Life Course as Determinants of Breast Cancer Risk
Mechanisms of Breast Cancer Development
Possible Biologic Mechanisms for Alterations in Breast Cancer Risk Associated with Obesity
A Need to Consider Timing of Exposure Across the Life Course
6 OPPORTUNITIES FOR ACTION TO REDUCE ENVIRONMENTAL RISKS FOR BREAST CANCER
Recognizing Uncertainty of Benefits and Risks
Evidence-Based Opportunities for Action to Reduce Risk
Likely Opportunities to Act to Reduce Risk of Breast Cancer
Assessing the Potential Impact of Risk Reduction Efforts
7 RECOMMENDATIONS FOR FUTURE RESEARCH
Applying a Life Course Perspective to Research on Breast Cancer
Testing to Identify Potential Breast Carcinogens
Understanding Breast Cancer Risks
APPENDIXES
B Biographical Sketches of Committee Members
C Classification Systems Used in Evidence Reviews
D Summary Table on Estimates of Population Attributable Risk
F Ionizing Radiation Exposure to the U.S. Population, with a Focus on Radiation from Medical Imaging *
*Appendix F is available online at http://www.nap.edu/catalog.php?record_id=13263.
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C-1 Compilation of Evidence Categories Used by Selected Organizations
C-2 Supplemental Criteria Used by IARC and WCRF/AICR in Evaluation of Evidence
D-1 Summary of Estimates of Population Attributable Risk for Risk Factors for Breast Cancer
F-1 Selected Units of Ionizing Radiation
F-2 Summary of U.S. Population’s Annual Exposure to Ionizing Radiation from Different Sources, 2006–2010
F-3 Typical Effective Doses of Radiation for Common Conventional X-ray and CT Procedures
F-4 Typical Annual Occupational Exposures to Radiation
F-5 Estimated Number of Future Breast Cancers That Might Occur Related to a Single Year of Medical Radiation Exposure
FIGURES
2-2 Age-adjusted incidence of invasive and in situ breast cancer in women, United States, 1975–2008
2-4 Multiple levels on which environmental exposures may act to influence breast cancer
F-1 Energy spectrum of radiation
F-2 Sample doses of and exposures to ionizing radiation
F-3 Proportion of radiation from various sources, 1985 (left) and 2006 (right)
F-4 Median effective radiation dose (interquartile range, minimum, and maximum) for each type of CT study
F-5 Estimated range in the lifetime attributable risk of cancer if a 20-year-old woman underwent one of several types of CT studies using observed radiation dose
F-6 Projected number of future cancers (mean and 95% uncertainty limits) that could be related to CT scan use in the United States in 2007, according to cancer type
BOXES
S-2 Environmental Factors Included in the Committee’s Evidence Review
3-1 Environmental Factors Included in the Committee’s Evidence Review
5-2 Nongenomic Estrogen Receptor Signaling by Environmental Estrogens
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ACS |
American Cancer Society |
|
ADH |
alcohol dehydrogenase |
|
ADI |
acceptable daily intake |
|
AFFF |
aqueous fire fighting foams |
|
AFP |
alpha fetoprotein |
|
AhR |
aryl hydrocarbon receptor |
|
AHRQ |
Agency for Healthcare Research and Quality |
|
AICR |
American Institute for Cancer Research |
|
ALDH |
aldehyde dehydrogenase |
|
AMPK |
AMP-activated protein kinase |
|
AR |
attributable risk |
|
ASTDR |
Agency for Toxic Substances and Disease Registry |
|
ATH |
adipose tissue hypoxia |
|
BaP |
benzo[a]pyrene |
|
BBD |
benign breast disease |
|
BCAC |
Breast Cancer Association Consortium |
|
BMI |
body mass index |
|
BPA |
bisphenol A |
|
BPC3 |
Breast and Prostate Cancer Cohort Consortium |
|
CAR |
constitutive androstate receptor |
|
CDC |
Centers for Disease Control and Prevention |
|
CFR |
Code of Federal Regulations |
|
CGEMS |
Cancer Genetic Markers of Susceptibility project |
CI |
confidence interval |
|
CISNET |
Cancer Intervention and Surveillance Modeling Network |
|
CT |
computed tomography |
|
CTS |
California Teachers Study |
|
CYP |
cytochrome P-450 |
|
DAG |
directed acyclic graphs |
|
DBP |
disinfection by-products |
|
DCIS |
ductal carcinoma in situ |
|
DDE |
dichlorodiphenyldichloroethylene |
|
DDT |
dichlorodiphenyltrichloroethane |
|
DEHP |
di(2-ethylhexyl) phthalate; also bis(2-ethylhexyl) phthalate |
|
DEP |
diethyl phthalate |
|
DES |
diethylstilbestrol |
|
DHEA |
dehydroepiandrosterone |
|
DINP |
diisononyl phthalate |
|
DMBA |
7,12-dimethylbenz[a]anthracene |
|
DNA |
deoxyribonucleic acid |
|
DSHEA |
Dietary Supplement Health and Education Act |
|
ECA |
European Chemical Agency |
|
ECM |
extracellular matrix |
|
EDC |
endocrine disrupting compound |
|
EFSA |
European Food Safety Authority |
|
EGFR |
epidermal growth factor receptor |
|
ELF-EMF |
extremely low frequency electromagnetic field |
|
EPA |
Environmental Protection Agency |
|
ER |
estrogen receptor |
|
ER– |
estrogen receptor negative |
|
ER+ |
estrogen receptor positive |
|
ERE |
estrogen response element |
|
FAO |
Food and Agriculture Organization of the United Nations |
|
FDA |
Food and Drug Administration |
|
FSH |
follicle stimulating hormone |
|
GAO |
Government Accountability Office |
|
GST |
glutathione S-transferase |
|
GWAS |
genome-wide association studies |
|
HER |
human epidermal growth factor receptor |
|
HERS |
Heart and Estrogen/Progestin Replacement Study |
HHS |
Department of Health and Human Services |
|
HPA axis |
hypothalamic–pituitary–adrenal axis |
|
HPG axis |
hypothalamic–pituitary–gonadal axis |
|
HPV program |
High Production Volume Chemical program |
|
HR |
hazard ratio |
|
HT |
hormone therapy |
|
IARC |
International Agency for Research on Cancer |
|
IGF |
insulin-like growth factor |
|
IGFBP |
insulin-like growth factor binding protein |
|
IOM |
Institute of Medicine |
|
IPCS |
(WHO) International Program on Chemical Safety |
|
LH |
leutenizing hormone |
|
MAPK |
mitogen-activated protein kinase |
|
MBzP |
monobenzyl phthalate |
|
MCPP |
mono-(3-carboxylpropyl) phthalate |
|
MEP |
monoethyl phthalate |
|
MMTV |
mouse mammary tumor virus |
|
MNU |
N-methyl-N-nitrosourea; also N-nitroso-N-methylurea |
|
MPA |
medroxyprogesterone acetate |
|
MQSA |
Mammography Quality Standards Act |
|
MRFIT |
Multiple Risk Factor Intervention Trial |
|
mRNA |
messenger RNA |
|
NAS |
National Academy of Sciences |
|
NAT |
N-acetyltransferase |
|
NCI |
National Cancer Institute |
|
NHANES |
National Health and Nutrition Examination Survey |
|
NHS |
Nurses’ Health Study |
|
NIAAA |
National Institute on Alcohol Abuse and Alcoholism |
|
NIEHS |
National Institute of Environmental Health Sciences |
|
NIH |
National Institutes of Health |
|
NNH |
number needed to harm |
|
NNT |
number needed to treat |
|
NPCR |
National Program of Cancer Registries |
|
NRC |
National Research Council |
|
NTP |
National Toxicology Program |
|
OEHHA |
Office of Environmental Health Hazard Assessment |
|
OR |
odds ratio |
|
OSHA |
Occupational Safety and Health Administration |
OVX |
ovariectomized |
|
PAH |
polycyclic aromatic hydrocarbon |
|
PAR |
population attributable risk |
|
PBDE |
polybrominated diphenyl ether |
|
PCB |
polychlorinated biphenyl |
|
PDQ |
Physician Data Query |
|
PFOA |
perfluorooctanoic acid |
|
PFOS |
perfluorooctanesulfonic acid |
|
PI3K |
phosphoinositide 3-kinase |
|
PND |
postnatal day |
|
PPAR |
peroxisome proliferator-activated receptor |
|
ppm |
parts per million |
|
PR |
progesterone receptor |
|
PR– |
progesterone receptor negative |
|
PR+ |
progesterone receptor positive |
|
PSA |
prostate specific antigen |
|
REACH |
Registration, Evaluation, Authorisation and Restriction of Chemical Substances |
|
RNA |
ribonucleic acid |
|
ROC |
receiver operating characteristic |
|
ROS |
reactive oxygen species |
|
RR |
relative risk |
|
SEER |
Surveillance, Epidemiology, and End Results Program |
|
SERD |
selective estrogen receptor down-regulator |
|
SERM |
selective estrogen receptor modulator |
|
SHBG |
sex hormone binding globulin |
|
SNP |
single nucleotide polymorphism |
|
STAR |
Study of Tamoxifen and Raloxifene |
|
TCDD |
2,3,7,8-tetrachlorodibenzo-p-dioxin |
|
TDLU |
terminal duct lobular unit |
|
TNBC |
triple negative breast cancer |
|
TNF |
tumor necrosis factor |
|
TSCA |
Toxic Substances Control Act |
|
USPSTF |
U.S. Preventive Services Task Force |
|
UV |
ultraviolet radiation |
|
VOC |
volatile organic compound |
WCRF |
World Cancer Research Fund |
|
WECARE |
Women’s Environment, Cancer, and Radiation Epidemiology Study |
|
WHI |
Women’s Health Initiative |
|
WHO |
World Health Organization |
|
XOR |
xanthine oxidoreductase |