title: Human epidermal growth factor receptor 2 overexpression as a prognostic factor in a large tissue microarray series of node-negative breast cancers.
abstract: OBJECTIVE
  Human epidermal growth factor receptor 2 gene (HER2) is associated with a poorer outcome in node-positive breast cancer, but the results are conflicting in node-negative disease. This study assessed the prognostic impact of HER2 overexpression/amplification in a large series of node-negative breast cancers.
  
  
  METHODS
  A tissue microarray (TMA) series was constructed consisting of 4,444 invasive breast cancers diagnosed in British Columbia from 1986 to 1992. Within this series, 2,026 patients were node negative, of whom 70% did not receive adjuvant systemic therapy. The TMA series was assessed for estrogen receptor (ER) and HER2. Logistic regression modeling was used to estimate odds ratios at the 10-year follow-up.
  
  
  RESULTS
  HER2 was positive in 10.2% of the node-negative cohort. In this cohort, an inferior outcome was seen in patients with HER2-positive tumors compared with HER2-negative tumors for 10-year relapse-free survival (RFS; 65.9% v 75.5%, respectively; P = .01), distant RFS (71.2% v 81.8%, respectively; P = .004), and breast cancer-specific survival (BCSS; 75.5% v 86.3%, respectively; P = .001). A trend for a worse overall survival was also seen (P = .06). HER2 was an independent poor prognostic factor for RFS and BCSS at 10 years, with odds ratios of 1.71 (P = .01) and 2.03 (P = .003), respectively. The number of HER2-positive tumors that were <or= 1 cm was small, but there was a trend for a worse outcome in T1b tumors.
  
  
  CONCLUSIONS
  HER2 overexpression/amplification is correlated with a poorer outcome in node-negative breast cancer. Larger studies are needed to more clearly define the prognostic impact of HER2 in tumors <or= 1 cm, particularly within the separate hormone receptor subgroups.
authors.affiliation: Division of Medical Oncology, Breast Cancer Outcomes Unit, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada. schia@bccancer.bc.ca
authors.forename: Stephen
authors.initials: S
authors.lastname: Chia
authors.forename: Brian
authors.initials: B
authors.lastname: Norris
authors.forename: Caroline
authors.initials: C
authors.lastname: Speers
authors.forename: Maggie
authors.initials: M
authors.lastname: Cheang
authors.forename: Blake
authors.initials: B
authors.lastname: Gilks
authors.forename: Allen M
authors.initials: AM
authors.lastname: Gown
authors.forename: David
authors.initials: D
authors.lastname: Huntsman
authors.forename: Ivo A
authors.initials: IA
authors.lastname: Olivotto
authors.forename: Torsten O
authors.initials: TO
authors.lastname: Nielsen
authors.forename: Karen
authors.initials: K
authors.lastname: Gelmon
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D001955:British Columbia; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D018570:Risk Assessment; D013997:Time Factors; D046888:Tissue Array Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D000068878:Trastuzumab; C508053:ERBB2 protein, human