Cancer genetics: Risks and mechanisms of cancer in women with inherited susceptibility to epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is a highly lethal malignancy, mostly due to the fact that the majority of cases are not detected until the disease has progressed to an advanced stage. The reason for this is that unlike endometrial cancer and cervical cancers, there are no unique symptoms associated with early (and more treatable) disease and there is currently no effective screening protocol. While most cases of EOC are not associated with an inherited predisposition, a small percentage of cases are so characterized, with such women at an increased risk not only for developing EOC but also for developing the disease at an earlier age than is observed in the general population. Nonetheless, there are effective interventions to reduce the likelihood of developing EOC. In high-risk women, consideration of such interventions should be entertained during the reproductive years; however, these interventions either temporarily (e.g., breast feeding, oral contraceptives) or permanently (e.g., tubal ligation, bilateral salpingo-oophorectomy) prevent pregnancy. It is thus imperative to identify such women early so as to offer preventive measures; conversely, the offering of such interventions must be coordinated with a frank discussion of pregnancy aspirations and family planning. Currently, the optimal approach to determine a women's risk for developing EOC is evaluating one's family history and offering genetic testing to those women at increased risk for having mutations in cancer susceptibility genes associated with EOC. While oncofertility is usually associated with individuals currently being treated for cancer, women at increased risk for developing EOC based on a genetic predisposition should likewise be considered for oncofertility counseling and potentially for novel fertility-sparing interventions.