Abstract IA09: Challenges in the identification of inherited risk of ovarian cancer

Abstract

Abstract We have come a long way since the 1990s in our understanding of inherited risk and in the genetic testing options that are available to our patients. Despite the clear benefits of identifying inherited risk, there are many barriers in place to genetic testing, and most women with ovarian cancer are still not undergoing these tests. The need for genetic testing currently exceeds the availability of genetic counselors, and creative solutions will need to be explored. The Stand Up To Cancer Ovarian Cancer Dream Team is conducting the MAGENTA (MAking GENetic Testing Accessible) trial. MAGENTA utilizes genetic testing at home with a mailed kit, electronic results delivery, and telephonic genetic counseling. This and other ideas will have to be explored in order to increase genetic testing rates. With the recent publication of SOLO-1 demonstrating a large benefit for PARP inhibitor maintenance therapy in the primary setting for women with advanced BRCA-mutated OC, identifying germline and somatic BRCA1 and BRCA2 mutations at the time of diagnosis is paramount and likely to soon be considered standard of care for treatment planning. The most optimal method for detecting both germline and somatic mutations is currently up for debate. Our University of Washington Department of Laboratory Medicine is currently offering tumor and germline sequencing in parallel using both tumor and blood samples, allowing for simultaneous detection of germline and somatic mutations, with methods optimized for each approach. Data from this ongoing project will be presented. Finally, in order to optimize the identification of inherited risk, we need to better understand which genes are implicated in ovarian cancer risk and treatment response. The advent of multiplex gene testing has allowed us to detect mutations in many genes using a single test, increasing efficiency and decreasing costs. The primary downside of multiplex testing is that as more genes are sequenced, the likelihood of identifying uncertain results also increases, either in the form of variants of uncertain significance (VUS) or damaging mutations in genes with uncertain contributions to cancer risk. Available data on risks of ovarian cancer with mutations in genes other than BRCA1 and BRCA2 will be reviewed. Citation Format: Barbara M. Norquist. Challenges in the identification of inherited risk of ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr IA09.