Oral contraceptive use and breast cancer risk: A cohort study of BRCA1 and BRCA2 mutation carriers

Background: BRCA1 and BRCA2 mutation carriers are at high risk of breast and ovarian cancer. Oral contraceptive preparations (OCPs) may reduce ovarian cancer risk, but its effect on breast cancer risk remains unclear. Methods: Combined data from three cohorts of 5705 BRCA1 and 3521 BRCA2 mutation carriers (IBCCS, BCFR and kConFab) were analyzed using age-dependent Cox regression models stratified for study and birth cohort. We conducted the first prospective analyses on this topic. Our additional main retrospective analyses were leftcensored 5 years preceding date of baseline questionnaire to control for survival bias. The full-cohort retrospective analyses, without left-censoring, was performed to compare results with the literature. Prospective analyses were considered most valid, while retrospective analyses were most powerful. Results: For BRCA1 mutation carriers we found no association between ever OCP use and risk of breast cancer in the prospective analyses (HR=1.08, 95% CI 0.75-1.56), but 23% and 27% increased risks for ever OCP use in the left-censored and full retrospective analyses, respectively. Retrospectively, an increasing trend for longer duration of use, especially before first full-term pregnancy (FFTP) was found (left-censored analyses: 10 years HR 1.41 (95%CI 1.10-1.813), p-trend=0.001 for duration of use before FFTP). For BRCA2 mutation carriers we found a positive association between ever OCP use and risk of breast cancer prospectively (HR=1.75, 95% CI 1.03-2.97), but retrospectively findings were inconsistent (HR=1.06, 95% CI 0.85-1.33 and HR=1.52, 95% CI 1.28-1.81 for the left-censored and full analyses, respectively). Conclusion: For BRCA1 mutation carriers the discrepancy between results of prospective and retrospective analyses may be explained by time since last OCP use before FFTP. Thus, a temporal increased risk of breast cancer following longer duration of OCP use before FFTP cannot be ruled out. The discordant findings between prospective and retrospective analyses for BRCA2 carriers could not be explained. Because of the lack of scientific clarity it is too early to give an unequivocal advice on OCP use with respect to breast cancer risk to BRCA1 and BRCA2 mutation carriers.