Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Mutations in BRCA1 and BRCA2.
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Phillips Kelly-Anne, Kotsopoulos Joanne, Domchek Susan M, Terry Mary Beth, Chamberlain James A, Bassett Julie K, Aeilts Amber M, Andrulis Irene L, Buys Saundra S, Cui Wanda, Daly Mary B, Eisen Andrea F, Foulkes William D, Friedlander Michael L, Gronwald Jacek, Hopper John L, John Esther M, Karlan Beth Y, Kim Raymond H, Kurian Allison W, Lubinski Jan, Metcalfe Kelly, Nathanson Katherine L, Singer Christian F, Southey Melissa C, Symecko Heather, Tung Nadine, Narod Steven A, Milne Roger L, Kathleen Cuningham Foundation Consortium for Research Into Familial Breast Cancer, the Risk Factor Analysis of Hereditary Breast and Ovarian Cancer Study, the Basser Center University of Pennsylvania Registry, and the Breast Cancer Family Registry, Kathleen Cuningham Foundation Consortium for Research Into Familial Breast Cancer, the Risk Factor Analysis of Hereditary Breast and Ovarian Cancer Study, the Basser Center University of Pennsylvania Registry and the Breast Cancer Family Registry
Аннотация
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.