Germline genetic testing in patients with uterine serous carcinoma at a tertiary academic center.

Abstract

e17640 Background: There is emerging evidence for germline genetic contribution to cases of uterine serous carcinoma (USC). Cohort studies of individuals carrying BRCA1 or BRCA2 pathogenic variants have shown higher risks of USC than expected. Starting in 2023, the NCCN hereditary cancer testing guidelines state that genetic testing may be considered in patients with USC, but a lack of testing may be hindering our assessment of endometrial cancer genetic risks. This study aimed to study our institutional genetic testing rates and results over the past five years. Methods: The electronic medical records of a tertiary academic center were digitally searched to identify all patients diagnosed with USC and treated by the gynecologic oncology division between January 1, 2019 and December 31, 2023. Medical records were then manually abstracted to confirm inclusion and collect data on demographics, cancer pathology and staging, family history, genetic counseling referral and testing outcomes, and follow-up. Descriptive statistics were performed with comparison testing using Fisher’s exact tests. Results: 109 cases of USC were diagnosed and treated between 2019 and 2023, 35 (32%) stage I disease, 8 (7%) stage 2, 24 (22%) stage III, and 42 (39%) with stage IV by FIGO 2009 staging. 74 patients (67.9%) were not referred for genetic testing. 6 (5.5%) had prior genetic testing completed before their USC diagnosis (primarily due to another primary cancer diagnosis), with a pathogenic variant prevalence of 67.7% (4/6). Of 30 patients referred for genetic counseling after their USC diagnosis, only 21 (70%) ultimately underwent genetic testing with a pathogenic variant prevalence of 28.6% (6/21). Pathogenic variants identified spanned 9 potentially actionable genes (Table 1). Patients with a prior personal history of cancer were more likely to have a pathogenic variant identified on testing (56.3% vs. 9.1%, p=0.018). Patients with a personal or family history of cancer were more likely to be referred for genetic counseling (47.8% vs. 23.1%, p=0.34 and 40% vs. 20%, p=0.04, respectively). Conclusions: Genetic counseling and germline testing for patients diagnosed with uterine serous carcinoma has not been widely implemented. Of those tested at our single institution, there was a high prevalence of potentially actionable pathogenic variants, and wider testing will help us better quantify and address these genetic risks. Germline genetic testing results in patients diagnosed with uterine serous carcinoma between 2019 and 2023. N (total 27) % No pathogenic variant identified 17 63.0% BRCA2 2 7.4% BRCA1 1 3.7% APC 1 3.7% ATM 1 3.7% BRIP1 1 3.7% CHEK2 1 3.7% MSH2 1 3.7% MSH6 1 3.7% PMS2 1 3.7%