Oral Contraceptives and Risk of Ovarian and Breast Cancers in BRCA Mutation Carriers: a Meta-analysis

Prophylactic salpingo-oophorectomy is currently the only effective strategy available for decreasing ovarian cancer risk in BRCA1/2 mutation carriers. Significantly decreased risk of ovarian cancer associated with the use of combined oral contraceptives (COCs) was shown in the general population, which could be an alternative approach for those who do not accept risk-reducing surgery. Cohort, case-control and case-case studies published in English up to December 2009 reporting the association of ovarian or breast cancer risk with the use of COCs and presenting BRCA status were selected for meta-analysis. Meta-analysis of three case-control studies showed a significant risk reduction of ovarian cancer in BRCA1/2 mutation carriers who were associated with any past COC use (odds ratio [OR]: 0.57; 95% CI: 0.47-0.70; p < 0.001) and significant trend by duration of COC use (OR: 0.95; 95% CI: 0.93-0.97; p < 0.001). No significant increase in breast cancer risk associated with COC use has been found in case-control studies in BRCA1 (OR: 1.08; p = 0.250), in BRCA2 (OR: 1.03; p = 0.788) mutation carriers or in case-case studies in BRCA1/2 carriers (OR: 0.80; p = 0.147). Significantly increased risk of breast cancer was only shown on a subset of cohort studies in BRCA1 mutation carriers (OR: 1.48; 95% CI: 1.14-1.92). In conclusion, meta-analysis confirmed significantly decreased ovarian cancer risk in BRCA1/2 mutation carriers associated with the use of COCs comparable to the relative extent shown in the general population. Data on the risk of breast cancer associated with COC use in BRCA mutation carriers are heterogeneous and results are inconsistent. COCs can be considered as an alternative strategy in the chemoprevention of ovarian cancer in BRCA1 mutation carriers who do not accept prophylactic salpingo-oophorectomy above the age of 30 years.