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The frequency of homologous recombination deficiency (HRD) and the clinical relevance of these alterations in patients with endometrial cancer (EC) are unknown. The aim of this study was to assess the incidence of HRD and its impact on the clinical characteristics and prognosis in patients with EC. Tumors with pathogenic and/or potentially pathogenic mutations in 10 genes (BRCA1, BRCA2, ATM, BARD1, BRIP1, PALB2, RAD51C, RAD51D, CHEK2, and CDK12) involved in the homologous recombination pathway in the MSK-MET and The Cancer Genome Atlas (TCGA) EC cohorts were considered to have HRD, and the others were considered to be homologous recombination proficient (HRP). The correlation between HRD status and the clinical characteristics of patients with EC was evaluated. The analyses were conducted in microsatellite stable (MSS) and microsatellite instability-high (MSI-H) populations, respectively. Of the 1315 patients with EC enrolled in the MSK-MET cohort, 163 (12.4%) patients had HRD and 1152 (87.6%) patients were HRP. HRD occurred more frequently in MSI-H patients than in MSS patients (28.7% vs. 9.8%, P < 0.001). Among patients with MSS, compared to patients in the HRP group, patients in the HRD group had a younger median age at EC diagnosis (60.4 vs. 64.6 years, P < 0.001), and were more likely to have endometrioid carcinoma (73.0% vs. 56.0%, P = 0.003), POLE mutation (40.5% vs. 1.4%, P < 0.001), or high tumor mutational burden (62.2% vs. 11.3%, P < 0.001). Tumors with HRD had a significantly lower rate of TP53 mutation than HRP tumors (30.6% vs. 49.4%, P < 0.001). HRD did not significantly alter the overall survival of patients with MSS tumors in either the MSK-MET cohort or the TCGA cohort. Tumors with HRD are a subtype of MSS EC with unique clinical and molecular characteristics. The evaluation of HRD in patients with MSS EC may help clinicians select patients who may benefit from targeted therapies. The potential clinical efficacy of agents targeting the homologous recombination system in this subgroup is worthy of study.
Shen et al. (Sat,) studied this question.