Comparative Analysis of Homologous Recombination Repair Status Across Gynecologic and Breast Cancers in Chinese Populations

Background: Homologous recombination deficiency (HRD) is a key genomic hallmark in multiple malignancies, driving genomic instability and influencing responsiveness to targeted therapies such as PARP inhibitors. While HRD has been extensively studied in cancers such as breast and ovarian carcinoma, its associations with broader genomic characteristics across diverse female-specific tumor types, including endometrial and cervical carcinoma, remain less well defined. Methods: Utilizing a 520-gene next-generation sequencing (NGS) panel, we conducted a retrospective analysis of genomic mutational profiles and HRD scores in 270 patients, including those with breast carcinoma (BRCA), ovarian carcinoma (OV), cervical carcinoma (CCA), and uterine corpus endometrial carcinoma (UCEC). Correlations between mutated genes, tumor mutation burden (TMB), microsatellite instability status, and genomic HRD scores were further analyzed. Results: BRCA, OV, and CCA exhibit comparable median HRD scores, which are significantly higher than those observed in UCEC. Within the HR gene spectrum, deficiencies in BRCA1/2 and mutations in PALB2 were associated with high HRD scores (≥42). Notably, a subset of patients without germline or somatic mutations in BRCA1/2, PALB2, or other HR-related genes also displayed high HRD. Further analysis revealed that, in BRCA, mutations in SMARCA4, EPHA5, and JAK2 may serve as potential HRD markers, whereas in OV, PIK3CA mutations could indicate a negative association. Additionally, TP53 mutations were linked to high HRD scores in BRCA, OV, and UCEC patients, while no such association was observed in CCA patients. Conclusion: The mutational patterns affecting homologous recombination repair differ across gynecologic and breast cancers. Further research into cancer-specific HRD mechanisms is warranted.