Testing Patterns and Prevalence of gBRCA Mutations among Women with Breast Cancer: A Cross-Sectional Observational Study

Abstract Pathogenic germline mutations in BRCA (gBRCAm) genes can heighten the risk of breast cancer (BC) among carriers. Economic constraints and patient testing hesitancy challenge adherence to hereditary germline testing guidelines. As a result, clinicians prioritize hereditary BC screening based on patient willingness, affordability, and therapeutic benefit. The objectives of the study were (1) to identify the pattern of hereditary cancer germline testing among women diagnosed with BC and (2) to determine the prevalence of gBRCAm among the women with BC who underwent hereditary cancer germline testing. A retrospective study was conducted at a cancer hospital between October 2023 and January 2024. We aimed to assess the germline testing patterns of physicians in our hospital by examining the clinical profile of patients with BC who underwent hereditary cancer multigene (30 gene panel) mutation testing using next-generation sequencing between January 2021 and December 2023. A simultaneous analysis was performed with a multiplex ligation-dependent probe amplification to detect deletions and duplications in the BRCA1 and BRCA2 genes. The classification of the variants as pathogenic and variants of uncertain significance (VUS) was determined by the American College of Medical Genetics and Genomics guideline. Of the 3,600 patients with BC during this study period, only 325 (9%) underwent germline testing. The testing patterns indicated that the median age of those tested was 48.4 years (standard deviation [SD]: 10.1; range: 20–77), 189 patients (58.2%) were younger than 50 years, and 103 patients (31.7%) had a family history of cancer. Family history of BC was reported in 95 (29.2%) patients. Bilateral BC was noted in 19 patients (5.8%), while ovarian cancer was reported in 9 (2.8%) patients. Triple-negative BC (TNBC), hormone receptor–positive BC, and HER2-positive BC were reported in 52, 42.8, and 17.2% patients, respectively. Pathogenic/likely pathogenic (P/LP) germline BRCA mutations were detected in 48 (14.7%) patients (BRCA1 in 29/325 [8.9%] patients and BRCA2 in 19/325 [5.8%] patients). The highest prevalence was seen among TNBC (36/169, 21.3%) patients. P/LP gBRCAm prevalence among those with and without notable family history was 27/103 (26.2%) and 21/222 (9.5%), respectively; age less than 50 years and greater than 51 years was noted in 32/189 patients (16.9%) and 16/136 (11.8%) patients, respectively. VUS was noted in 29 patients (BRCA1 in 4 patients [8.9%] and BRCA2 in 25 patients). Measures to ensure equitable access to genetic testing can improve testing rates and enhance patient outcomes through personalized care.