Evaluation of the BRCAness phenotype and its correlations with clinicopathological features in triple-negative breast cancers

Abstract

Some sporadic triple-negative breast cancers (TNBCs) share similar clinicopathological and molecular characteristics to BRCA1/2-mutant breast cancers, a phenotype described as "BRCAness." Identifying BRCAness in TNBCs could expand the target group for platinum salts and poly(adenosine diphosphate-ribose) polymerase inhibitors. The aims of our study were to assess the clinical validity of BRCA1/2 promoter methylation and BRCA1-like genomic profile to identify BRCAness and to evaluate its correlations with clinicopathological features in TNBCs. Formalin-fixed, paraffin-embedded tissues and fresh tissues of 151 primary invasive TNBCs were collected. BRCA1/2 promoter methylation and BRCA1-like genomic profile were detected using methylation-specific multiplex ligation-dependent probe amplification and multiplex ligation-dependent probe amplification assay, respectively. BRCA1/2 messenger RNA expression was evaluated by quantitative reverse-transcription polymerase chain reaction. Of the 151 patients, 38 (25.2%) showed BRCA1 promoter methylation. Of the 124, 52 (41.9%) had a BRCA1-like multiplex ligation-dependent probe amplification profile. The frequency of BRCAness phenotype was 54.8% (68/124). BRCA1 germline mutation and BRCA1 promoter methylation were mutually exclusive (P = .002). The BRCAness phenotype was significantly associated with large tumor size (>2 cm, P = .009), positive lymph nodes (P = .008), grade 3 tumor (P = .0001), high Ki-67 levels (P = .001), and basal-like breast cancers (P = .0001). Combined detections of BRCA1 promoter methylation and BRCA1-like genomic profile could identify more BRCAness cases in TNBCs. BRCA1 promoter methylation might rule out BRCA1 germline mutation in TNBCs. BRCAness was associated with aggressive clinicopathological features. These findings might have clinical values in hereditary breast cancer screening and target treatment of TNBCs.

Keywords: BRCA1 promoter methylation; BRCA1-like genomic profile; BRCA1/2 mutation; BRCAness; Triple-negative breast cancers.