Homologous recombination deficiency in high-grade serous ovarian carcinoma: clinical pathological characteristics, impact of neoadjuvant chemotherapy, and prognostic implications.

Abstract

Objective: To investigate the clinicopathological and prognostic significance of homologous recombination deficiency (HRD) in high-grade serous ovarian carcinoma (HGSC) and evaluate the impact of neoadjuvant chemotherapy (NACT) on HRD detection.

Methods: HRD status was assessed in 126 surgically resected HGSC samples (30 post-NACT, 96 primary surgery) using the AmoyDx^® HRD Complete Panel. HRD positivity was defined as a pathogenic/likely pathogenic BRCA1/2 mutation and/or genomic scar score (GSS) ≥45. Correlations with clinicopathological variables, histological subtypes (classic vs. solid, endometrial-like, and transitional [SET] patterns), and survival were analyzed.

Results: HRD positivity was detected in 76 (60.3%) cases, with BRCA1/2 mutations in 26.2%. HRD-positive tumors showed larger size (p=0.034) and more SET patterns (p=0.001). Notably, among BRCA1/2 wild-type patients, the NACT group showed significantly lower HRD positivity (22.2% vs. 56.1%; p=0.003) and decreased median GSS (19.5 vs. 55.2; p<0.001) than the primary surgery group. Multivariate analysis identified HRD positivity (hazard ratio [HR]=0.488; p=0.023) and first-line maintenance therapy (HR=0.435; p=0.008) predicted better progression-free survival (PFS), while lymph node metastasis predicted worse PFS (HR=2.674; p=0.001). R0 resection improved both PFS (HR=0.410; p=0.006) and overall survival (HR=0.074; p=0.013).

Conclusion: HRD status is a prognostic biomarker in HGSC. Its correlation with SET patterns supports histology as an initial screening tool. Importantly, NACT is correlated with reduced detectable HRD positivity and lower GSS, underscoring the need for HRD testing before chemotherapy to ensure accurate assessment and guide treatment.