Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Mutations in and .

Purpose: It is uncertain whether, and to what extent, hormonal contraceptives increase breast cancer (BC) risk for germline or mutation carriers.

Methods: Using pooled observational data from four prospective cohort studies, associations between hormonal contraceptive use and BC risk for unaffected female and mutation carriers were assessed using Cox regression.

Results: Of 3,882 and 1,509 mutation carriers, 53% and 71%, respectively, had ever used hormonal contraceptives for at least 1 year (median cumulative duration of use, 4.8 and 5.7 years, respectively). Overall, 488 and 191 mutation carriers developed BC during median follow-up of 5.9 and 5.6 years, respectively. Although for mutation carriers, neither current nor past use of hormonal contraceptives for at least 1 year was statistically significantly associated with BC risk (hazard ratio [HR], 1.40 [95% CI, 0.94 to 2.08], = .10 for current use; 1.16 [0.80 to 1.69], = .4, 1.40 [0.99 to 1.97], = .05, and 1.27 [0.98 to 1.63], = .07 for past use 1-5, 6-10, and >10 years before, respectively), ever use was associated with increased risk (HR, 1.29 [95% CI, 1.04 to 1.60], = .02). Furthermore, BC risk increased with longer cumulative duration of use, with an estimated proportional increase in risk of 3% (1%-5%, = .002) for each additional year of use. For mutation carriers, there was no evidence that current or ever use was associated with increased BC risk (HR, 0.70 [95% CI, 0.33 to 1.47], = .3 and 1.07 [0.73 to 1.57], = .7, respectively).

Conclusion: Hormonal contraceptives were associated with increased BC risk for mutation carriers, especially if used for longer durations. Decisions about their use in women with mutations should carefully weigh the risks and benefits for each individual.