Serum epidermal growth factor receptor/HER-2 predicts poor survival in patients with metastatic breast cancer

Cancer. 2006 Nov 15;107(10):2337-45. doi: 10.1002/cncr.22255.


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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / blood*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / mortality*
  • Carcinoma / blood*
  • Carcinoma / drug therapy
  • Carcinoma / mortality*
  • Double-Blind Method
  • ErbB Receptors / therapeutic use
  • Female
  • Humans
  • Letrozole
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Metastasis / diagnosis
  • Neoplasm Metastasis / drug therapy
  • Nitriles / therapeutic use
  • Prognosis
  • Receptor, ErbB-2 / blood*
  • Survival Analysis
  • Tamoxifen / therapeutic use
  • Triazoles / therapeutic use


  • Antineoplastic Agents
  • Nitriles
  • Triazoles
  • Tamoxifen
  • Letrozole
  • ErbB Receptors
  • Receptor, ErbB-2