title: Triple-negative breast cancer: distinguishing between basal and nonbasal subtypes.
abstract: OBJECTIVE
  Triple-negative (TN; estrogen receptor, progesterone receptor, and HER-2 negative) cancer and basal-like breast cancer (BLBC) are associated with poor outcome and lack the benefit of targeted therapy. It is widely perceived that BLBC and TN tumors are synonymous and BLBC can be defined using a TN definition without the need for the expression of basal markers.
  
  
  METHODS
  We have used two well-defined cohorts of breast cancers with a large panel of biomarkers, BRCA1 mutation status, and follow-up data to compare the clinicopathologic and immunohistochemical features of TN tumors expressing one or more of the specific basal markers (CK5/6, CK17, CK14, and epidermal growth factor receptor; BLBC) with those TN tumors that express none of these markers (TN3BKE-).
  
  
  RESULTS
  Here, we show that although the morphologic features of BLBC are not significantly different from that of TN3BKE- tumors, BLBC showed distinct clinical and immunophenotypic differences. BLBC showed a statistically significant association with the expression of the hypoxia-associated factor (CA9), neuroendocrine markers, and other markers of poor prognosis such as p53. A difference in the expression of cell cycle-associated proteins and biomarkers involved in the immunologic portrait of tumors was seen. Compared with TN3BKE- tumors, BLBC was positively associated with BRCA1 mutation status and showed a unique pattern of distant metastasis, better response to chemotherapy, and shorter survival.
  
  
  CONCLUSIONS
  TN breast cancers encompass a remarkably heterogeneous group of tumors. Expression of basal markers identifies a biologically and clinically distinct subgroup of TN tumors, justifying the use of basal markers (in TN tumors) to define BLBC.
authors.affiliation: Department of Histopathology, Nottingham City Hospital NHS Trust, Nottingham University, Nottingham, United Kingdom. emadrakha@yahoo.com
authors.forename: Emad A
authors.initials: EA
authors.lastname: Rakha
authors.forename: Somaia E
authors.initials: SE
authors.lastname: Elsheikh
authors.forename: Muhammed A
authors.initials: MA
authors.lastname: Aleskandarany
authors.forename: Hany O
authors.initials: HO
authors.lastname: Habashi
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Green
authors.forename: Desmond G
authors.initials: DG
authors.lastname: Powe
authors.forename: Maysa E
authors.initials: ME
authors.lastname: El-Sayed
authors.forename: Ahmed
authors.initials: A
authors.lastname: Benhasouna
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Brunet
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
authors.forename: Andy J
authors.initials: AJ
authors.lastname: Evans
authors.forename: Roger
authors.initials: R
authors.lastname: Blamey
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis