title: Epidermal growth factor receptor expression in breast cancer association with biologic phenotype and clinical outcomes.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) expression is associated with aggressive phenotypes in preclinical breast cancer models, but in clinical studies, EGFR has been inconsistently linked to poor outcome. We hypothesized that EGFR expression in human breast tumors, when centrally and uniformly assessed, is associated with an aggressive phenotype and resistance to systemic therapy.
  
  
  METHODS
  In a database of 47,286 patients with breast cancer, EGFR status was known on 2567 tumors. EGFR levels were measured centrally by ligand binding assay, and tumors with > or =10 fmol/mg were prospectively deemed positive. Clinical and biological features of EGFR-positive and EGFR-negative tumors were compared. Clinical outcomes were assessed by systemic therapy status.
  
  
  RESULTS
  Of 2567 tumors, 475 (18%) were EGFR positive. EGFR-positive tumors were more common in younger and in black women, were larger, had a higher S-phase fraction, and were more likely to be aneuploid. EGFR-positive tumors were more likely to be HER2-positive (26% vs 16%, P < .0001), but less likely to be estrogen receptor-positive (60% vs 88%, P < .0001) or progesterone receptor-positive (26% vs 65%, P < .0001). In multivariate analyses, EGFR expression independently correlated with worse disease-free survival (hazard ratio [HR] = 1.66; 95% confidence interval [CI], 1.4-2.41, P = .007) and overall survival (HR = 1.98, 95% CI, 1.36-2.88, P = .0004) in treated patients, but not in untreated patients.
  
  
  CONCLUSIONS
  EGFR expression is more common in breast tumors in younger and black women. It is associated with lower hormone receptor levels, higher proliferation, genomic instability, and HER2 overexpression. It is correlated with higher risk of relapse in patients receiving adjuvant treatment. Blocking EGFR may improve outcome in selected patients.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX, USA. rimawi@bcm.edu
authors.forename: Mothaffar F
authors.initials: MF
authors.lastname: Rimawi
authors.forename: Priya B
authors.initials: PB
authors.lastname: Shetty
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Weiss
authors.forename: Rachel
authors.initials: R
authors.lastname: Schiff
authors.forename: C Kent
authors.initials: CK
authors.lastname: Osborne
authors.forename: Gary C
authors.initials: GC
authors.lastname: Chamness
authors.forename: Richard M
authors.initials: RM
authors.lastname: Elledge
mesh_terms: D000367:Age Factors; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism*; D005006:Ethnicity; D005260:Female; D005629:Frozen Sections; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism; D010641:Phenotype; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D066246:ErbB Receptors