Use of the Utah population database to evaluate statewide use of genetic testing for hereditary breast/ovarian cancer.

e22529 Background: Genetic testing for hereditary breast/ovarian cancer (HBOC) continues to be underutilized, and options for population-based assessment of testing barriers and outcomes are lacking. This project uses linkages between statewide data sources available through the Utah Population Database (UPDB) to establish an infrastructure for studying the use of HBOC cancer genetic testing across a state. Methods: Clinical HBOC testing data from 1994-2018 was obtained for the University of Utah Huntsman Cancer Institute, Intermountain Healthcare, Utah Cancer Specialists, and the Salt Lake Veterans administration via electronic imports of tests attributed to these healthcare systems from three commercial laboratories. Genetic testing was linked to external data through the UPDB to determine demographic and urban/rural designation. Cancer diagnoses were obtained from the Utah Cancer Registry, and genealogies from the Utah Resource for Genetic and Epidemiology Research. These variables were matched to data available for the individual at the date of testing. For individuals with multiple genetic tests, the date for the first test was used. Results: Testing data was available for 12983 individuals who linked to additional records within the UPDB. Tested individuals were 86% White, 9% Hispanic, and 16% lived in rural/frontier areas. 75% of tests were performed between 2011-2018. 1575 (12%) had >1 pathogenic variant (PVs) identified in an HBOC gene, with the majority of PVs being in BRCA1/2 (89%), and TP53, CHEK2, and ATM each accounting for 2% of PVs. 7178 cancers were diagnosed in 5980 individuals (46%, avg. 1.2 cancer/person). Cancer cases were evaluated to determine if National Comprehensive Cancer Network (HBOC 2018) criteria were met. Cancer cases who have a relative with BC < 50 years of age or a relative with ovarian cancer (OC) were more likely to have a have BRCA1/2 PV than cases not meeting those criteria (17.5% vs 6.1% and 22.3% vs. 6.3% respectively). Cancer cases meeting criteria due to family history of pancreatic cancer also had a higher rate of PVs (13.1% vs. 8.4%) predominately due to additional PVs in BRCA2. Conclusions: This project begins to address the challenge of population assessment of HBOC genetic testing. We established a regulatory infrastructure to share testing data between multiple healthcare systems. In collaboration with commercial laboratories, genetic testing data was obtained in a consistent, discrete format even though it is stored differently within each health care system. The majority (54%) of HBOC testing in Utah is happening in people who did not have cancer at the time of their test, and focusing on assessing testing of cancer patients will not provide comprehensive information on testing done in the state. Among individuals with cancer, access to family history information is crucial for assessing the rate of PVs and utility of testing criteria.

High Prevalence of Germline Mutations in Cancer Susceptibility Genes in Thai Patients with Clinical Spectrum of Hereditary Breast-Ovarian Cancer Syndrome

Background: Germline genetic mutation plays a significant role in breast cancer susceptibility. The strength of such predisposition varies among ethnic groups across the globe, and clinical data from Asian population to develop a strategic approach to who should undergo a genetic test are lacking. Methods: We performed a multigene test with next generation sequencing in our 5-year hereditary breast-ovarian cancer spectrum cohort consists of 306 breast cancer patients, 62 ovarian cancer patients, 14 pancreatic cancer patients and 7 prostatic cancer patients. Results: There were 83 pathogenic/likely pathogenic (P/LP) variants identified in 104 patients, 44 of these P/LP variants were novel. We reported a high rate of germline P/LP variants in breast cancer (24%), ovarian cancer (37%), pancreatic cancer (14%), and prostatic cancer (29%). Germline P/LP variants in BRCA1 and BRCA2 accounted for 80% of P/LP variants found in breast cancer and 57% of P/LP variants found in ovarian cancer. The detection rate of NCCN 2019 guideline for genetic/familial high-risk assessment of breast and ovarian cancers was 22-40%. Conclusion: Overall, the data from this study strongly support the consideration of multigene panel test as a diagnostic tool for patients with hereditary breast-ovarian cancer spectrum in Thailand.