Clinical and Pathological Characteristics of Breast Cancer Cases with Germline Alterations in Homologous Recombination Defect-associated Genes

Cancer Cases with Germline Alterations in Homologous Recombination Defect-associated Genes Aim: Approximately 5-10% of breast cancer (BC) cases are hereditary, most frequently associated with germline variants in homologous recombination repair (HRR) genes such as BRCA1/2.However, non-BRCA HRR gene alterations, including ATM gene and CHEK2, may also influence tumor biology and clinical outcomes.This study aimed to evaluate the clinical relevance of germline homologous recombination deficiency (HRD)related variants in BC and to compare the clinicopathological features and survival outcomes between BRCA and non-BRCA carriers.Methods: A retrospective cohort of 148 BC patients with germline HRD-related variants identified by next-generation sequencing between 2018 and 2022 was analyzed.Variants were classified according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology 2015 criteria.Clinical, pathological, and survival data were assessed using descriptive statistics and Kaplan-Meier survival analysis with the Log-Rank test.Results: Of 148 patients (mean age 45.210.1 years), 80 (54%) carried BRCA variants and 68 (46%) non-BRCA variants, most frequently ATM and CHEK2.Pathogenic or likely pathogenic variants were more frequent in BRCA carriers (77.5% vs. 58.8%,p=0.014).Disease-free survival (DFS) did not differ significantly between BRCA and non-BRCA groups (p=0.42).Prophylactic mastectomy and oophorectomy were performed significantly more often in BRCA carriers (p<0.05).Conclusions: Although DFS was comparable between BRCA and non-BRCA carriers, relapse was more frequent in BRCA1 and pathogenic variant carriers.These results emphasize the clinical importance of integrating germline HRR gene analysis into personalized surveillance and management strategies in BC.