Data from Location of Mutation in <i>BRCA2</i> Gene and Survival in Patients with Ovarian Cancer

Abstract

<div>Abstract<p><b>Purpose:</b> BRCA2 plays a central role in homologous recombination by loading RAD51 on DNA breaks. The objective of this study is to determine whether the location of mutations in the RAD51-binding domain (RAD51-BD; exon 11) of <i>BRCA2</i> gene affects the clinical outcome of ovarian cancer patients.</p><p><b>Experimental Design:</b> A study cohort of 353 women with ovarian cancer who underwent genetic germline testing for <i>BRCA1</i> and <i>BRCA2</i> genes was identified. Progression-free survival (PFS), platinum-free interval (PFI), and overall survival (OS) were analyzed. The Cancer Genome Atlas (TCGA) cohort of ovarian cancer (<i>n</i> = 316) was used as a validation cohort.</p><p><b>Results:</b> In the study cohort, 78 patients were carriers of germline mutations of <i>BRCA2</i>. After adjustment for FIGO stage and macroscopic residual disease, <i>BRCA2</i> carriers with truncating mutations in the RAD51-BD have significantly prolonged 5-year PFS [58%; adjusted HR, 0.36; 95% confidence interval (CI), 0.20–0.64; <i>P</i> = 0.001] and prolonged PFI (29.7 vs. 15.5 months, <i>P</i> = 0.011), compared with noncarriers. <i>BRCA2</i> carriers with mutations located in other domains of the gene do not have prolonged 5-year PFS (28%, adjusted HR, 0.67; 95% CI, 0.42–1.07; <i>P</i> = 0.094) or PFI (19 vs. 15.5 months, <i>P</i> = 0.146). In the TCGA cohort, only <i>BRCA2</i> carriers harboring germline or somatic mutations in the RAD51-BD have prolonged 5-year PFS (46%; adjusted HR, 0.30; 95% CI, 0.13–0.68; <i>P</i> = 0.004) and 5-year OS (78%; adjusted HR, 0.09; 95% CI, 0.02–0.38; <i>P</i> = 0.001).</p><p><b>Conclusions:</b> Among ovarian cancer patients, <i>BRCA2</i> carriers with mutations located in the RAD51-BD (exon 11) have prolonged PFS, PFI, and OS. <i>Clin Cancer Res; 24(2); 326–33. ©2017 AACR</i>.</p></div>