Age-related distribution of homologous recombination deficiency in advanced ovarian carcinoma: a large real-world French cohort.

Abstract

Objective: Tumor genetic testing for BRCA and homologous recombination repair is essential for guiding maintenance therapy in high-grade non-mucinous ovarian carcinomas. While clinical trials (PAOLA-1, PRIMA, ATHENA-MONO, PRIME) have reported homologous recombination deficiency rates of 44% to 67% in cohorts with a median age of 61, real-world data suggest age-related variations. We aimed to evaluate homologous recombination deficiency prevalence in a large French population and hypothesized a distribution pattern similar to the recent German findings published in 2022, in which older age correlated with lower homologous recombination deficiency rates.

Methods: We retrospectively analyzed advanced ovarian carcinoma cases referred to the Dijon Cancer Center from 191 care centers between 2022 and 2024 for Myriad MyChoice homologous recombination deficiency testing. Data collected included age, histologic type, homologous recombination deficiency status, homologous recombination proficiency status, and genomic instability scores. We compared the distribution of homologous recombination deficiency and HRP tumors in women <60 and ≥60 years using the χ² test.

Results: In 1322 advanced ovarian carcinoma cases with a median age of 70.1 years, the overall rates were 35.3% homologous recombination deficiency and 64.7% homologous recombination proficiency. A sub-analysis of 1226 high-grade cases (median age 70.4; including high-grade serous carcinoma, clear-cell carcinoma, undifferentiated carcinomas, and carcinosarcoma) showed 36.5% homologous recombination deficiency and 63.5% homologous recombination proficiency. Notably, patients aged ≥60 years had a significantly higher likelihood of presenting with a homologous recombination proficiency tumor compared with those aged <60 years (65.8% vs 53.2%, p < .001). Among 42 clear-cell carcinoma cases, 97.6% exhibited homologous recombination proficiency status.

Conclusions: In this large real-world cohort of advanced ovarian carcinoma, we observed a notably higher prevalence of homologous recombination proficiency tumors compared to the 4 clinical trials reported in the literature, with homologous recombination proficiency incidence increasing significantly with age. Given that older patients predominantly present with homologous recombination proficiency tumors, which are associated with poorer survival, treatment strategies should be adjusted to better address the specific needs of this demographic.