sábado, 27 de octubre de 2018

Evaluation of the BRCAness phenotype and its correlations with clinicopathologic features in triple-negative breast cancers. - PubMed - NCBI

2018 Oct 16. pii: S0046-8177(18)30390-3. doi: 10.1016/j.humpath.2018.10.004. [Epub ahead of print]

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

Tian T1, Shan L1, Yang W1, Zhou X1, Shui R2.

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Abstract

Some sporadic triple-negative breast cancers (TNBCs) share similar clinicopathologic and molecular characteristics with 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 (PARP) inhibitors. The aim of our study was to assess the clinical validity of BRCA1/2 promoter methylation and BRCA1-like genomic profile to identify BRCAness, and to evaluate its correlations with clinicopathologic features in TNBCs. Formalin-fixed, paraffin-embedded (FFPE) 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 (MS-MLPA) and multiplex ligation-dependent probe amplification (MLPA) assay respectively. BRCA1/2 mRNA expression were evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 25.2% (38/151) patients showed BRCA1 promoter methylation. 41.9% (52/124) had a BRCA1-like MLPA profile. The frequency of BRCAness phenotype was 54.8% (68/124). BRCA1-germline mutation and BRCA1 promoter methylation were mutually exclusive (P = 0.002). The BRCAness phenotype was significantly associated with large tumor size (>2 cm, P = 0.009), positive lymph nodes (P = 0.008), grade 3 tumor (P = 0.0001), high Ki67 levels (P = 0.001) and basal-like breast cancers (P = 0.0001). 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 clinicopathologic features. These findings might have clinical values in hereditary breast cancer screening and target treatment of TNBCs.