BRCA1 and BRCA2 Mutation Carriers, Oral Contraceptive Use, and Breast Cancer Before Age 50

^{1 1}Department of Preventive Medicine, University of Southern California-Keck School of Medicine, Los Angeles, California; ²Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California; ³Northern California Cancer Center, Fremont, California; ⁴Early Detection Laboratory, ⁵University of Melbourne, Melbourne, Victoria, Australia; ⁶Fox Chase Cancer Center, Philadelphia, Pennsylvania; ⁷Department of Hematology-Oncology, University of Utah, Salt Lake, Utah; ⁸Mailman School of Public Health, Columbia University, New York, New York; ⁹Cancer Care Ontario; ¹⁰Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; ¹¹University of Otago, Dunedin, New Zealand; ¹²Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, Victoria, Australia; ¹³Hereditary Cancer Clinic, Prince of Wales University, Sydney, New South Wales, Australia; ¹⁴Department of Cancer Biology, Harvard Medical School/Dana-Farber Cancer Institute, Boston, Massachusetts; and ¹⁵Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia

^* To whom correspondence should be addressed. E-mail: haile{at}usc.edu.

	Abstract

Background: Understanding the effect of oral contraceptives on risk of breast cancer in BRCA1 or BRCA2 mutation carriers is important because oral contraceptive use is a common, modifiable practice.

Methods: We studied 497 BRCA1 and 307 BRCA2 mutation carriers, of whom 195 and 128, respectively, had been diagnosed with breast cancer. Case-control analyses were conducted using unconditional logistic regression with adjustments for family history and familial relationships and were restricted to subjects with a reference age under 50 years.

Results: For BRCA1 mutation carriers, there was no significant association between risk of breast cancer and use of oral contraceptives for at least 1 year [odds ratio (OR), 0.77; 95% confidence interval (95% CI), 0.53-1.12] or duration of oral contraceptive use (P_trend = 0.62). For BRCA2 mutation carriers, there was no association with use of oral contraceptives for at least 1 year (OR, 1.62; 95% CI, 0.90-2.92); however, there was an association of elevated risk with oral contraceptive use for at least 5 years (OR, 2.06; 95% CI, 1.08-3.94) and with duration of use (OR_trend per year of use, 1.08; P = 0.008). Similar results were obtained when we considered only use of oral contraceptives that first started in 1975 or later.

Conclusions: We found no evidence overall that use of oral contraceptives for at least 1 year is associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers before age 50. For BRCA2 mutation carriers, use of oral contraceptives may be associated with an increased risk of breast cancer among women who use them for at least 5 years. Further studies reporting results separately for BRCA1 and BRCA2 mutation carriers are needed to resolve this important issue. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1863-1870)

Key Words: Breast Cancer, BRCA1, BRCA2, EPIDEMIOLOGY, Genetics of Risk and Outcome

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