Clinical Management of BRCA Mutation Carriers
There has been great interest in determining whether a similar benefit extends to women who are at increased genetic risk of ovarian cancer. A multicenter study of 799 ovarian cancer patients with BRCA1 or BRCA2 mutations, and 2,424 control patients without ovarian cancer but with a BRCA1 or BRCA2 mutation, showed a significant reduction in ovarian cancer risk with use of oral contraceptives (OR, 0.56; 95% CI 0.45-0.71). Compared to never use of oral contraceptives, duration up to 1 year was associated with an OR of 0.67 (95% CI 0.50-0.89). The OR for each year of oral contraceptive use was 0.95 (95% CI 0.92-0.97) with a maximum observed protection at 3 years to 5 years of use. This study included women from a prior study by the same authors and confirmed the results of that prior study. A population-based case-control study of ovarian cancer did not find a protective benefit of oral contraceptive use in BRCA1 or BRCA2 mutation carriers, (OR = 1.07 for ?5 years of use), though they were protective, as expected, among noncarriers (OR = 0.53 for ?5 years of use). A small population-based case-control study of 36 BRCA1 mutation carriers, however, observed a similar, protective effect in both mutation carriers and noncarriers (OR = approximately 0.5). A multicenter study of subjects drawn from numerous registries observed a protective effect of oral contraceptives among the 147 BRCA1 or BRCA2 mutation carriers, with ovarian cancer compared with the 304 matched mutation carriers without cancer (OR = 0.62 for ?6 years of use). Finally, a meta-analysis of 18 studies including 13,627 BRCA mutation carriers, of whom 2,855 had breast cancer and 1,503 had ovarian cancer, reported a significantly reduced risk of ovarian cancer (summary relative risk = 0.50; 95% CI, 0.33-0.75) associated with oral contraceptive use. The authors also reported significantly greater risk reductions with longer duration of oral contraceptive use (36% reduction in risk for each additional 10 years of oral contraceptive use). There was no association with breast cancer risk and use of oral contraceptive pills formulated after 1975.
Level of evidence: 3aii
Refer to the Reproductive Factors section of this summary for a discussion of oral contraceptive use and breast cancer in this population.
It has been suggested that incessant ovulation, with repetitive trauma and repair to the ovarian epithelium, increases the risk of ovarian cancer. In epidemiologic studies in the general population, physiologic states that prevent ovulation have been associated with decreased risk of ovarian cancer. It has also been suggested that chronic overstimulation of the ovaries by luteinizing hormone (LH) plays a role in ovarian cancer pathogenesis. Most of these data derive from studies in the general population, but some information suggests the same is true in women at high risk due to genetic predisposition.