title: Prognostic value of basal phenotype in HER2-overexpressing breast cancer.
abstract: BACKGROUND
  Primary breast cancers that overexpress human epidermal growth factor receptor 2 have variable biological features and clinical outcomes. A subgroup of HER2-overexpressing tumors that express basal-like immunohistochemical markers-the so-called basal-HER2+ subtype--is associated with poor prognosis. We investigated the clinical relevance of this basal-HER2+ subtype within HER2-overexpressing breast tumors.
  
  
  METHODS
  Database review identified consecutive patients with HER2-overexpressing breast cancer. Archival tumor specimens from these patients were immunostained for estrogen receptor (ER), HER2, and basal cytokeratin (CK) expression, then subtyped as luminal-HER2+ (ER positive and basal CK negative), HER2+ (ER negative and basal CK negative), and basal-HER2+ (ER negative and basal CK positive). Subtypes were correlated with clinicopathologic features and overall survival.
  
  
  RESULTS
  Immunohistochemical assessment of 131 HER2-overexpressing breast tumors identified 79 (60%) luminal-HER2+ tumors, 40 (31%) HER2+ tumors, and 12 (9%) basal-HER2+ tumors. There was no difference in the use of adjuvant trastuzumab and chemotherapy among patients with these subtypes. Five-year overall survival was 65% for patients with basal-HER2+ tumors versus 94% (P = 0.0035) and 96% (P = 0.0031) for patients with luminal-HER2+ and HER2+ tumors, respectively. The basal-HER2+ subtype was associated with the worst prognosis after adjusting for age, tumor size, lymph node status, and adjuvant treatment (hazard ratio 5.06, 95% confidence interval 1.1-23.2, P = 0.037).
  
  
  CONCLUSIONS
  The basal-HER2+ subtype highlights the heterogeneous biology of HER2-overexpressing breast cancer. The basal-HER2+ subtype is independently associated with poor survival and may provide insight into breast cancer cell response to anti-HER2 therapy.
authors: Department of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, CA, USA.
authors: Sanjay P
authors: SP
authors: Bagaria
authors: Partha S
authors: PS
authors: Ray
authors: Jinhua
authors: J
authors: Wang
authors: Luisa
authors: L
authors: Kropcho
authors: Alice
authors: A
authors: Chung
authors: Myung-Shin
authors: MS
authors: Sim
authors: Jaime M
authors: JM
authors: Shamonki
authors: Silvana
authors: S
authors: Martino
authors: Xiaojiang
authors: X
authors: Cui
authors: Armando E
authors: AE
authors: Giuliano
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000378:metabolism* / Q000401:mortality; D018270:Carcinoma, Ductal, Breast / Q000145:classification / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D015996:Survival Rate
chemical_list: D007633:Keratins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen