Introduction/Background BRCA1/2 pathogenic variant (PV) carriers have a high risk of breast and ovarian cancer. Contraceptives impact these risks in the general population. Among BRCA1/2-PV carriers, sufficient data and clear recommendations regarding contraceptives are lacking. We investigated how contraceptives modify breast and ovarian cancer risk in BRCA1/2-PV carriers.
Methodology We investigated the risk ratio for developing breast cancer or ovarian cancer in BRCA1/2-PV carriers who have used contraception (any kind) versus BRCA1/2-PV carriers who have not. A systematic search identified studies describing breast and/or ovarian cancer risk in BRCA1/2-PV carriers as modified by contraception. Random-effects meta-analyses were used to estimate pooled effects for breast and ovarian cancer risk separately. Subgroup analyses were conducted for BRCA1 versus BRCA2 and per contraceptive.
Results Meta-analysis of 11 studies, including 25,857 women, reveals that breast cancer risk may be increased by the oral contraceptive pill, depending on outcome measure: hazard ratio 1.43 (95% confidence interval (CI) 1.25–1.63) and odds ratio 1.06 (95% CI 0.90–1.25), and the risk remains increased after cessation of use. Meta-analysis of 10 studies with 21,425 women shows that ovarian cancer risk is decreased among oral contraceptive pill users: HR 0.62 (95% CI 0.52; 0.74) and OR 0.49 (95% CI 0.38; 0.63) and the protective effect vanishes after cessation of use. Tubal ligation protects against ovarian cancer (HR 0.44 (95% CI 0.26; 0.74) and OR 0.74 (0.53; 1.03)). Data regarding other contraceptives were unavailable. No differences were observed between BRCA1 and BRCA2-PV carriers.
Conclusion The oral contraceptive pill potentially increases breast cancer risk, while ovarian cancer risk decreases by both the oral contraceptive pill and tubal ligation in BRCA1/2-PV carriers. Counselling of BRCA1/2-PV carriers about contraceptives should be a personalized weighing of genetic and non-genetic factors and patients’ preferences.
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