Familial Gynecologic Cancers: Whom to Screen and How to Manage?

Abstract

Gynecologic cancers are important components of several hereditary cancer syndromes. Identification of individuals who harbor germline mutations in cancer susceptibility genes is important not only for prevention in unaffected family members but also for the cancer patient, in terms of therapeutic implications and prevention of second cancers. While significant strides have been made in the identification of women with Hereditary Breast/Ovarian Cancer and Lynch syndrome, several questions remain in terms of whom to offer genetic testing, how to screen for cancers, and the best way to reduce cancer risk. This chapter addresses these issues from different viewpoints. Screening all patients with high-grade serous ovarian cancer for BRCA1/2 germline mutations is one strategy that could improve counseling for patients regarding disease course, treatment options, prevention of second cancers, and prevention of cancers in family members who may also harbor BRCA mutations. However, given the current cost of genetic testing, this strategy may not be cost-effective in the healthcare system. Reflex tumor testing for Lynch syndrome, with immunohistochemistry or microsatellite instability analysis, can increase the detection of Lynch-associated endometrial cancers and prevention of secondary cancers, most notably colorectal cancer. However, several questions remain regarding the optimal strategy and implementation of reflex testing in all endometrial cancer patients. Based on the current understanding of the tubal origin of BRCA-associated ovarian cancers, risk-reducing salpingectomy is an attractive option for younger patients with BRCA1/2 mutations in whom fertility is a concern. Unfortunately, there is no objective evidence that the substantial risk reduction seen with risk-reducing salpingo-oophorectomy would be translated to risk-reducing salpingectomy. Many questions remain regarding screening BRCA1/2 mutation carriers with CA-125 and ultrasound every 6 months. Ongoing, large prospective trials will likely help to answer some of these questions. Until then, patients do need to understand the drawbacks of our current screening methods, especially when considering risk-reducing salpingo-oophorectomy. There is a paucity of evidence when considering endometrial cancer screening in patients with Lynch syndrome; however, annual endometrial biopsy remains one option. As we understand more about familial gynecologic cancers, including Hereditary Breast/Ovarian Cancer and Lynch syndrome, large prospective studies are needed to help address current screening guidelines and management recommendations for these patients.