title: BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer.
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.
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hitomi
authors.identifier: http://orcid.org/0000-0002-5416-5869
authors.initials: H
authors.lastname: Mori
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Breast Center, Kumamoto Shinto General Hospital, Kumamoto, Japan.
authors.forename: Reiki
authors.initials: R
authors.lastname: Nishimura
authors.affiliation: Breast Center, Kumamoto Shinto General Hospital, Kumamoto, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Osako
authors.affiliation: Department of Pathology, Kumamoto Shinto General Hospital, Kumamoto, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Arima
authors.affiliation: Department of Breast and Endocrine Surgery, Kumamoto City Hospital, Kumamoto, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Okumura
authors.affiliation: Department of Surgery, Hamanomachi Hospital, Fukuoka, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Okido
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Kai
authors.affiliation: Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kishimoto
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Otsuka
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D015415:Biomarkers; D017024:Chemotherapy, Adjuvant; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D015415:Biomarkers