Hormonal contraceptives and cancer risk in women with a BRCA1 or BRCA2 pathogenic variant.

Women with BRCA1/2 pathogenic variants face increased risks of breast and ovarian cancers. Our study aimed to evaluate the impact of hormonal contraceptive use on these risks. This matched cohort study included 1677 women who were found to carry a BRCA1/2 pathogenic variant. A Cox proportional hazards model was used to estimate hazard ratios associated with oral contraceptive use and with levonorgestrel-releasing intrauterine device use. Among BRCA1 carriers (n = 990), oral contraceptive use was not associated with breast cancer risk (HR = 0.90, 95% CI 0.77-1.05, p = 0.2). Among BRCA2 carriers (n = 687), oral contraceptive use was associated with reduced breast cancer risk (HR = 0.80, 95% CI 0.65-0.99, p = 0.04), although duration-stratified analyses did not demonstrate a consistent dose-response relationship. Oral contraceptive use was associated with a decrease in the risk of ovarian cancer in BRCA2 carriers (HR = 0.57, 95% CI 0.35-0.94, p = 0.028), with the strongest protective effect observed among BRCA2 carriers who used an oral contraceptive for more than 5 years (HR = 0.13; 95% CI 0.02-0.92). The protective effect of oral contraceptive use was less profound for BRCA1 carriers. The use of a levonorgestrel-releasing intrauterine device was not associated with breast or ovarian cancer risk. The use of an oral contraceptive was associated with reduced risks of breast and ovarian cancer among BRCA2 carriers, although the observed association with breast cancer should be interpreted cautiously given the absence of a consistent duration-response pattern. There was no increase in the risk of breast cancer among BRCA1 carriers who used an oral contraceptive. No association with either cancer was found among users of a levonorgestrel-releasing intrauterine device.