BRCA1 methylation impacts on the prognosis of patients with high-grade serous ovarian cancer

Abstract

Homologous recombination repair deficiency (HRD) is involved in the development of high-grade serous ovarian carcinoma (HGSOC) and its higher sensitivity to platinum-based chemotherapy. We have evaluated the HRD status, including BRCA mutations, genomic scar score, and methylation of BRCA1 in 352 HGSOCs. We then divided the HRD-positive cohort into molecular subgroups, the BRCA mutation cohort and BRCA1 methylation cohort and evaluated their first-line chemotherapy response and progression-free survival (PFS). The BRCA mutation group showed the best outcome in platinum therapy (ORR 96%), and the highest median PFS (46 months). Patients with BRCA1 methylation showed a significantly poorer outcome, with a median PFS of 19 months and a significantly lower ORR to platinum therapy (84%). In conclusion, methylation group had poor outcomes in terms of chemotherapy response, and PFS, requiring a more thorough follow-up.