Screening and Prevention of Hereditary Gynecologic Cancers

Endometrial and ovarian cancer are the fourth and fifth most common malignancies in women, with approximately 40,000 new endometrial and 25,000 new ovarian cancers expected to be diagnosed in the Unites States this year. While the majority of these cancers will occur in the absence of a family history, approximately 5% of endometrial cancers and 10% of ovarian cancers will be the result of inherited defects in high-penetrance cancer susceptibility genes. With the identification and subsequent availability of clinical genetic testing for mutations in the genes associated with hereditary breast–ovarian cancer and the Lynch/hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, targeted risk-reduction using intensive screening, chemoprevention, and prophylactic surgery has become possible for women at inherited risk of gynecologic malignancies. We review the options for gynecologic cancer risk reduction in women with an inherited mutation in BRCA1, BRCA2, or one of the mismatch repair (MMR) genes associated with Lynch/HNPCC syndrome. Additionally, we outline ongoing questions and areas for future research.