Oral Contraceptive Use and Risk of Early-Onset Breast Cancer in Carriers and Noncarriers of BRCA1 and BRCA2 Mutations
- Roger L. Milne1,
- Julia A. Knight5,
- Esther M. John7,
- Gillian S. Dite1,
- Ronald Balbuena8,
- Argyrios Ziogas8,
- Irene L. Andrulis6,
- Dee W. West7,
- Frederick P. Li10,
- Melissa C. Southey2,
- Graham G. Giles3,
- Margaret R.E. McCredie4,
- John L. Hopper1,
- Alice S. Whittemore9 and
- for the Breast Cancer Family Registry
- 1Centre for Genetic Epidemiology and 2Department of Pathology, The University of Melbourne; 3Cancer Epidemiology Centre, The Cancer Council Victoria, Carlton, Victoria, Australia; 4Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand; 5Samuel Lunenfeld Research Institute, Mount Sinai Hospital; 6Cancer Care Ontario, Toronto, Ontario, Canada; 7Northern California Cancer Center, Union City, California; 8Department of Medicine, Division of Epidemiology, University of California, Irvine, California; and 9Department of Health Research and Policy, Stanford University, Stanford, California; 10Dana-Faber Cancer Institute, Boston, Massachusetts
- Requests for reprints:
John Hopper, Centre for Genetic Epidemiology, The University of Melbourne, Level 2, 723 Swanston Street, Carlton, Victoria 3053, Australia. Phone: 61-3-8344-0697; Fax: 61-3-9349-5815. E-mail: j.hopper{at}unimelb.edu.au
Abstract
Background: Recent oral contraceptive use has been associated with a small increase in breast cancer risk and a substantial decrease in ovarian cancer risk. The effects on risks for women with germ line mutations in BRCA1 or BRCA2 are unclear.
Methods: Subjects were population-based samples of Caucasian women that comprised 1,156 incident cases of invasive breast cancer diagnosed before age 40 (including 47 BRCA1 and 36 BRCA2 mutation carriers) and 815 controls from the San Francisco Bay area, California, Ontario, Canada, and Melbourne and Sydney, Australia. Relative risks by carrier status were estimated using unconditional logistic regression, comparing oral contraceptive use in case groups defined by mutation status with that in controls.
Results: After adjustment for potential confounders, oral contraceptive use for at least 12 months was associated with decreased breast cancer risk for BRCA1 mutation carriers [odds ratio (OR), 0.22; 95% confidence interval (CI), 0.10-0.49; P < 0.001], but not for BRCA2 mutation carriers (OR, 1.02; 95% CI, 0.34-3.09) or noncarriers (OR, 0.93; 95% CI, 0.69-1.24). First use during or before 1975 was associated with increased risk for noncarriers (OR, 1.52 per year of use before 1976; 95% CI, 1.22-1.91; P < 0.001).
Conclusions: There was no evidence that use of current low-dose oral contraceptive formulations increases risk of early-onset breast cancer for mutation carriers, and there may be a reduced risk for BRCA1 mutation carriers. Because current formulations of oral contraceptives may reduce, or at least not exacerbate, ovarian cancer risk for mutation carriers, they should not be contraindicated for a woman with a germ line mutation in BRCA1 or BRCA2.
Footnotes
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Grant support: National Cancer Institute, NIH, under RFA CA-95-003 and through cooperative agreements with The University of Melbourne, Northern California Cancer Center, and Cancer Care Ontario, as part of the Breast Cancer Family Registry. The Australian Breast Cancer Family Study was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, and the Victorian Health Promotion Foundation. The recruitment of controls by the Northern California Cancer Center was supported in part by NIH grant U01CA 71966. The recruitment of controls in Ontario was supported by the Canadian Breast Cancer Research Initiative.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Note: The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of collaborating centers in the Breast Cancer Family Study, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the Breast Cancer Family Study.
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- Accepted September 20, 2004.
- Received May 17, 2004.
- Revision received September 10, 2004.
