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1 Centre for Genetic Epidemiology and 2 Department of Pathology, The University of Melbourne; 3 Cancer Epidemiology Centre, The Cancer Council Victoria, Carlton, Victoria, Australia; 4 Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand; 5 Samuel Lunenfeld Research Institute, Mount Sinai Hospital; 6 Cancer Care Ontario, Toronto, Ontario, Canada; 7 Northern California Cancer Center, Union City, California; 8 Department of Medicine, Division of Epidemiology, University of California, Irvine, California; and 9 Department of Health Research and Policy, Stanford University, Stanford, California; 10 Dana-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
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.
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