Multigene germline testing for epithelial ovarian cancer in China

BACKGROUND: Large-scale studies of germline variants in hereditary cancer susceptibility genes among Chinese epithelial ovarian cancer (EOC) patients remain limited. This study assessed the prevalence and clinical significance of germline variants in 21 genes relevant to hereditary breast and ovarian cancer. METHODS: In this multicenter prospective cohort (February 2017-December 2018), 961 unselected EOC patients underwent germline testing for 21 genes. Variant frequencies were compared with international data, and associations with clinicopathologic characteristics and survival outcomes were evaluated. RESULTS: Pathogenic or likely pathogenic (P/LP) variants were identified in BRCA1 (17.79%), BRCA2 (6.35%), and other homologous recombination (HR)-related genes (2.71%). P/LP variants in non-HR-related genes were rare (0.1%). BRCA1 and BRCA1/2 P/LP variant carriers were more likely to respond to platinum-based chemotherapy (p = .002 and p < .001). Variants of uncertain significance or higher (VUS+) in HR-related genes were associated with better overall survival (hazard ratio, 0.57; p = 0.004) and progression-free survival (hazard ratio, 0.75; p = 0.02), with a trend more pronounced than that observed for BRCA1/2 VUS + carriers. CONCLUSIONS: Over 25% of Chinese EOC patients carry germline HR-related gene variants, which are associated with better treatment response and survival. Broad genetic testing is critical, and the prognostic value of VUS warrants further investigation.