Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Mutations in <i>BRCA1</i> and <i>BRCA2</i>.

Abstract

It is uncertain whether, and to what extent, hormonal contraceptives increase breast cancer (BC) risk for germline <i>BRCA1</i> or <i>BRCA2</i> mutation carriers. Using pooled observational data from four prospective cohort studies, associations between hormonal contraceptive use and BC risk for unaffected female <i>BRCA1</i> and <i>BRCA2</i> mutation carriers were assessed using Cox regression. Of 3,882 <i>BRCA1</i> and 1,509 <i>BRCA2</i> 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 <i>BRCA1</i> and 191 <i>BRCA2</i> mutation carriers developed BC during median follow-up of 5.9 and 5.6 years, respectively. Although for <i>BRCA1</i> 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], <i>P</i> = .10 for current use; 1.16 [0.80 to 1.69], <i>P</i> = .4, 1.40 [0.99 to 1.97], <i>P</i> = .05, and 1.27 [0.98 to 1.63], <i>P</i> = .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], <i>P</i> = .02). Furthermore, BC risk increased with longer cumulative duration of use, with an estimated proportional increase in risk of 3% (1%-5%, <i>P</i> = .002) for each additional year of use. For <i>BRCA2</i> 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], <i>P</i> = .3 and 1.07 [0.73 to 1.57], <i>P</i> = .7, respectively). Hormonal contraceptives were associated with increased BC risk for <i>BRCA1</i> mutation carriers, especially if used for longer durations. Decisions about their use in women with <i>BRCA1</i> mutations should carefully weigh the risks and benefits for each individual.