Clinical Relevance of BRCA1 Promoter Methylation Testing in Patients with Ovarian Cancer

Purpose: Homologous recombination deficiency (HRD) is close- and negative for 48 patients. Using a 70% cutoff, 19% (15/79) of ly related to PARP inhibitor (PARPi) benefit in ovarian cancer. The BRCA wild-type ovarian cancer had high BRCA1 methylation levels. capacity of BRCA1 promoter methylation to predict prognosis and All of the highly methylated tumors were classified as HRD, HRD status remains unclear. We aimed to correlate BRCA1 pro-achieving a positive predictive value of 100%. We detected 14% moter methylation levels in patients with high-grade ovarian cancer (11/79) low-methylated tumors (1%–69%), and all of them were to HRD status and clinical behavior to assess its clinical relevance. also classified as HRD. Mean GIS was 61.5 for BRCAmut, 66.4 for Experimental Design: This is a retrospective monocentric anal-high-BRCAmeth, 58.9 for low-BRCAmeth, and 33.3 for BRCAwt ysis of patients centrally tested for genomic instability score (GIS) by unmethylated (P < 0.001). Low methylation levels detected in MyChoice CDx (Myriad Genetics). The detection of BRCA1 pro-samples previously exposed to chemotherapy appeared to be assomoter methylation and quantification of methylation levels were ciated with poor outcome post-platinum. performed by quantitative droplet digital PCR methodology. High Conclusions: Patients with ovarian cancer with high levels of BRCA1 methylation was defined as ≥70% and deemed to be BRCA1 hypermethylation are very likely to have high GIS and associated with homozygous silencing. therefore represent good candidates for PARPi treatment. These results Results: Of 100 patients, 11% harbored a deleterious BRCA1/2 may be highly relevant to other tumor types for HRD prediction. mutation. GIS was considered positive (score ≥ 42) for 52 patients See related commentary by Garg and Oza, p.