BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer

PLoS One. 2016 Dec 15;11(12):e0167016. doi: 10.1371/journal.pone.0167016. eCollection 2016.

Abstract

Background: Triple-negative breast cancer (TNBC) is a heterogeneous tumor that encompasses many different subclasses of the disease. In this study, we assessed BRCAness, defined as the shared characteristics between sporadic and BRCA1-mutated tumors, in a large cohort of TNBC cases.

Methods: The BRCAness of 262 patients with primary TNBCs resected between January 2004 and December 2014 was determined through the isolation of DNA from tumor tissue. Classification of BRCAness was performed using multiple ligation-dependent probe amplification (MLPA). The tumor subtypes were determined immunohistochemically using resected specimens.

Results: Of the 262 TNBCs, the results of the MLPA assays showed that 174 (66.4%) tumors had BRCAness. Patients with BRCAness tumors were younger than patients with non-BRCAness tumors (P = 0.003). There was no significant difference between the two groups regarding their pathological stages. The BRCAness group had a significantly shorter recurrence-free survival (RFS) compared with the non-BRCAness group (P = 0.04) and had a shorter overall survival (OS) although this did not reach statistical significance. Adjuvant treatments with anthracycline-based regimens provided significantly greater benefits to the BRCAness group (P = 0.003 for RFS, and P = 0.03 for OS). Multivariate Cox proportional hazard model analysis showed that BRCAness was an independent negative prognostic factor, and the anthracycline-based adjuvant chemotherapy was an independent positive prognostic factor for both RFS and OS in TNBC.

Conclusions: The 66.4% patients of TNBCs showed BRCAness. BRCAness is essential as a biomarker in the subclassification of TNBCs and might be of use for predicting their prognosis. Furthermore, this biomarker might be a predictive factor for the effectiveness of anthracycline-based adjuvant chemotherapy for patients with TNBCs.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Anthracyclines / therapeutic use*
  • Antibiotics, Antineoplastic / therapeutic use*
  • Biomarkers
  • Chemotherapy, Adjuvant*
  • Female
  • Genes, BRCA1*
  • Humans
  • Middle Aged
  • Mutation
  • Prognosis
  • Treatment Outcome
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Anthracyclines
  • Antibiotics, Antineoplastic
  • Biomarkers

Grants and funding

This work was supported by the Japan Society for the Promotion of Science, KAKENHI, and by the budget demand from Ministry of Education, Culture, Sports, Science and Technology, Japan, Grant number 20591550, https://www.jsps.go.jp/j-grantsinaid/ to Makoto Kubo, and by World premier COE (core of excellence) formation for the treatment and research of pancreatic cancer (there is no grant number), http://www.mext.go.jp/en/ to Takao Otsuka. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.