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