Patterns of confirmatory germline testing in patients with somatic BRCA1/2 pathogenic variants across solid tumor types in a community oncology setting.

Abstract

e23331 Background: Tumor mutation profiling serves as an essential diagnostic tool in oncology, facilitating the identification of targetable variants and informing treatment decisions. Somatic pathogenic / likely pathogenic (P/LP) variants in BRCA1 and BRCA2 (BRCA1/2) have been pivotal in guiding the use of PARP inhibitors for managing certain malignancies. Despite the established guidelines recommending germline testing upon the identification of somatic P/LP BRCA1/2 variants, adherence to confirmatory testing varies. Understanding the patterns of confirmatory germline testing across various cancer types in the community oncology setting is crucial for optimizing patient management, familial risk assessment, and treatment outcomes. Methods: This is a retrospective observational cohort study using data from electronic health records. The study population includes adult cancer patients within the US Oncology Network who underwent somatic tumor mutation profiling for solid tumors between November 1, 2021, and November 1, 2023, and were found to have a somatic P/LP BRCA1/2 variant. Descriptive analyses were conducted to evaluate patient characteristics, somatic testing results, and confirmatory germline testing rates, overall and by cancer type. Results: The study identified 526 cancer patients across participating US Oncology Network practices who had a P/LP BRCA1/2 variant identified on somatic tumor mutation profiling for solid tumors. The study population had a median age of 63 years (IQR 54 - 72) and was predominantly white (70%) across all cancer types. The three most common cancers were breast (19%), ovarian (13%), and non-small cell lung (13%). Overall, 55% of patients underwent confirmatory germline testing. Among those tested, 54% were confirmed to have germline P/LP BRCA1/2 variants (Table 1). Confirmatory testing rates were higher in BRCA1/2 associated cancers (breast, ovarian, prostate, pancreas) compared to other cancer types. Conclusions: Confirmatory germline testing remains suboptimal, particularly in cancer types less commonly associated with germline P/LP BRCA1/2 variants. This highlights the need for further education on testing in these patients. Improved awareness and adherence to testing guidelines are needed to ensure appropriate genetic risk assessment and personalized treatment strategies. Rates of confirmatory germline testing and germline BRCA1/2 positivity among the most common cancer types (n >25 patients). Patients with Somatic P/LP BRCA1/2,n (%) Overall526 Breast102 (19) Ovarian71 (13) NSCLC71 (13) Colon51 (10) Prostate35 (7) Endometrial33 (6) Pancreas28 (5) Germline Testing, n (%) 289 (55) 72 (71) 61 (86) 14 (20) 21 (41) 24 (69) 20 (61) 19 (68) Germline P/LP BRCA1/2 Confirmed, n (%) 157 (54) 49 (68) 40 (66) <10 <10 15 (62) <10 15 (79)