title: Serum epidermal growth factor receptor/HER-2 predicts poor survival in patients with metastatic breast cancer.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR, HER-1, and erbB1) is overexpressed in primary breast cancer and had been identified as a poor prognostic factor.
  
  
  METHODS
  Pretreatment serum EGFR levels were quantified by using an enzyme-linked immunoadsorbent assay in a Phase III first-line trial of letrozole and tamoxifen and were correlated with patient outcomes.
  
  
  RESULTS
  Serum EGFR levels in a control group of 117 healthy, postmenopausal women measured 64.1 +/- 13.3 ng/mL (mean +/- standard deviation). Using a cutoff EGFR level of 44.1 ng/mL from the control group (5% nonparametric method), 53 of 535 patients (10%) had decreased serum levels of EGFR. Patients with decreased serum EGFR had no significant difference in objective response rate (ORR), clinical benefit rate (CBR), time to progression (TTP), or time to treatment failure (TTF); however, they did have significantly reduced survival compared with patients who had normal serum EGFR levels (median survival, 23.3 months vs. 30.9 months; P = .007). A combined analysis of pretreatment serum EGFR and HER-2 yielded no additional predictive information for ORR, CBR, TTP, or TTF compared to serum HER-2 alone. However, in the current analysis, a subgroup of patients who had decreased serum EGFR and normal serum HER-2 was identified (n = 39 of 535 patients; 7.3%) that had significantly reduced survival compared with patients who had normal serum levels of both EGFR and HER-2 (median survival, 23.5 months vs. 37.1 months; P = .005). In multivariate analysis, a decreased serum EGFR level remained a significant independent prognostic factor for decreased survival (hazards ratio, 1.58; P = .007).
  
  
  CONCLUSIONS
  In patients who had metastatic breast cancer, decreased serum EGFR/normal serum HER-2 predicted shorter survival compared with patients who had normal levels of serum EGFR/HER-2. This patient subgroup deserves further study to assess their response to and selection for anti-EGFR-directed therapies.
authors.affiliation: Department of Hematology/Oncology, Hershey Medical Center, Pennsylvania State University, Hershey, Pennsylvania 17033, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Souder
authors.forename: Kim
authors.initials: K
authors.lastname: Leitzel
authors.forename: Suhail M
authors.initials: SM
authors.lastname: Ali
authors.forename: Laurence
authors.initials: L
authors.lastname: Demers
authors.forename: Dean B
authors.initials: DB
authors.lastname: Evans
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Chaudri-Ross
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hackl
authors.forename: Peter
authors.initials: P
authors.lastname: Hamer
authors.forename: Walter
authors.initials: W
authors.lastname: Carney
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D002277:Carcinoma / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D004311:Double-Blind Method; D066246:ErbB Receptors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000188:drug therapy; D009570:Nitriles / Q000627:therapeutic use; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000077289:Letrozole; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; D014230:Triazoles