© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 23, 1773-1779,
December 4, 2002
© 2002 Oxford University Press
ARTICLE |
Oral Contraceptives and the Risk of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers
Affiliations of authors: S. A. Narod, M.-P. Dubé, P. Sun, The Centre for Research on Women’s Health, University of Toronto, Ontario, Canada; J. Klijn, Daniel den Hoed Cancer Center and Erasmus University Medical Center, Rotterdam, The Netherlands; J. Lubinski, Pomeranian Medical University, Szczecin, Poland; H. T. Lynch, Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, NE; P. Ghadirian, Epidemiology Research Unit, Centre hospitalier de l’Université de Montréal (CHUM), Hôtel-Dieu, University of Montreal, Quebec, Canada; D. Provencher, Department of Obstetrics and Gynecology, Notre Dame Hospital, Montreal; K. Heimdal, P. Moller, Department of Cancer Genetics, Norwegian Radium Hospital, Oslo, Norway; M. Robson, K. Offit, Department of Human Genetics and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; C. Isaacs, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC; B. Weber, Departments of Medicine and Genetics, University of Pennsylvania, Philadelphia; E. Friedman, Oncogenetics Unit, Chaim Sheba Medical Center, Tel-Hashomer, Israel; R. Gershoni-Baruch, Institute of Genetics, Rambam Medical Center, Haifa, Israel; G. Rennert, National Cancer Control Center, Carmel Medical Center, Haifa; B. Pasini, Istituto Nazionale Tumori, Milan, Italy; T. Wagner, Department of Obstetrics and Gynecology, University of Vienna, Vienna, Austria; M. Daly, Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA; J. E. Garber, Dana-Farber Cancer Institute, Boston, MA; S. L. Neuhausen, Department of Medical Informatics, University of Utah, Salt Lake City; P. Ainsworth, London Regional Cancer Center, London, Ontario, Canada; H. Olsson, H. Jernstrom, The Jubileum Institute, Department of Oncology, Lund University Hospital, Lund, Sweden; G. Evans, St. Mary’s Hospital, Manchester, U.K.; M. Osborne, Strang Cancer Prevention Center, New York; F. Couch, Mayo Clinic, Rochester, MN; W. D. Foulkes, Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montreal; E. Warner, Sunnybrook and Womens College Health Sciences Centre, Toronto; C. Kim-Sing, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; O. Olopade, Center for Clinical Cancer Genetics, University of Chicago, Chicago, IL; N. Tung, Beth Israel Deaconess Hospital, Boston; H. M. Saal, Hereditary Cancer Program, Division of Human Genetics, Children’s Hospital Medical Center, Cincinnati, OH; J. Weitzel, City of Hope Hospital, Duarte, CA; S. Merajver, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; M. Gauthier-Villars, Service de Genetique-Oncologique, Institute Curie, Paris, France; J.-S. Brunet, Algorithme Pharma, Montreal.
Correspondence to: Steven A. Narod, M.D., Centre for Research on Women’s Health, 790 Bay St., Rm. 750, Toronto, Ontario M5G 1N8, Canada (e-mail: steven.narod{at}swchsc.on.ca).
Background: Oral contraceptive use has been associated with an increase in the risk of breast cancer in young women. We examined whether this association is seen in women at high risk of breast cancer because they carry a mutation in one of two breast cancer susceptibility genes, BRCA1 and BRCA2. Methods: We performed a matched case–control study on 1311 pairs of women with known deleterious BRCA1 and/or BRCA2 mutations recruited from 52 centers in 11 countries. Women who had been diagnosed with breast cancer were matched to control subjects by year of birth, country of residence, mutation (BRCA1 or BRCA2), and history of ovarian cancer. All study subjects completed a questionnaire about oral contraceptive use. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. All statistical tests were two-sided. Results: Among BRCA2 mutation carriers, ever use of oral contraceptives was not associated with an increased risk of breast cancer (OR = 0.94, 95% CI = 0.72 to 1.24). For BRCA1 mutation carriers, ever use of oral contraceptives was associated with a modestly increased risk of breast cancer (OR = 1.20, 95% CI = 1.02 to 1.40). However, compared with BRCA1 mutation carriers who never used oral contraceptives, those who used oral contraceptives for at least 5 years had an increased risk of breast cancer (OR = 1.33, 95% CI = 1.11 to 1.60), as did those who used oral contraceptives before age 30 (OR = 1.29, 95% CI = 1.09 to 1.52), those who were diagnosed with breast cancer before age 40 (OR = 1.38, 95% CI = 1.11 to 1.72), and those who first used oral contraceptives before 1975 (OR = 1.42, 95% CI = 1.17 to 1.75). Conclusions: Among BRCA1 mutation carriers, women who first used oral contraceptives before 1975, who used them before age 30, or who used them for 5 or more years may have an increased risk of early-onset breast cancer. Oral contraceptives do not appear to be associated with risk of breast cancer in BRCA2 carriers, but data for BRCA2 carriers are limited.
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