title: Basal phenotype identifies a poor prognostic subgroup of breast cancer of clinical importance.
abstract: BACKGROUND
  Breast cancer is recognised to be a heterogeneous disease with a range of morphological appearances and behaviours. The recently recognised basal phenotype (BP) is associated with poor survival, but the clinical implications of this class of breast cancers remain to be adequately defined.
  
  
  METHODS
  We have examined a well-characterised series of 1872 invasive breast carcinomas with a long term follow-up to assess the clinical significance of BP.
  
  
  RESULTS
  A pragmatic definition of the BP as immunophenotypic evidence of basal cytokeratins CK5/6 and/or CK14 expression was used. These tumours were associated with shorter overall survival and disease-free interval in our series as a whole and in both the lymph node (LN) negative and LN positive subgroups. When stratified by histological grade, BP was of highly significant prognostic value in grade 3 but not in grades 1 or 2 tumours. Similarly, it was associated with poor survival in the moderate group of the Nottingham prognostic Index but not in the other groups. In a subgroup comprising LN negative grade 3 tumours, BP was the most powerful prognostic marker followed only by tumour size, while the other variables were non-significant. Patients with BP were more likely to respond to chemotherapy than those with non-basal tumours.
  
  
  CONCLUSIONS
  Our results provide robust evidence that BP is an important class of breast cancers with a particularly aggressive behaviour in patients with LN negative grade 3 disease. We recommend routine identification of BP in breast cancer and the development of effective adjuvant treatment strategies. These are important observations as these tumours typically lack hormone receptor and HER-2 overexpression limiting the range of relevant adjuvant therapies.
authors.affiliation: Molecular Medical Sciences, University of Nottingham and Department of Histopathology and Surgery, Nottingham City Hospital NHS Trust, Hucknall Road, Nottingham, NG5 1PB, UK.
authors.forename: Emad A
authors.initials: EA
authors.lastname: Rakha
authors.forename: Dalia Abd
authors.initials: DA
authors.lastname: El-Rehim
authors.forename: Claire
authors.initials: C
authors.lastname: Paish
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Green
authors.forename: Andrew H S
authors.initials: AH
authors.lastname: Lee
authors.forename: John F
authors.initials: JF
authors.lastname: Robertson
authors.forename: Roger W
authors.initials: RW
authors.lastname: Blamey
authors.forename: Douglas
authors.initials: D
authors.lastname: Macmillan
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality / Q000473:pathology; D010641:Phenotype; D011379:Prognosis