Serum EGFR/HER-2 combination predicts poor survival in metastatic breast cancer.

9613 Background: Epidermal growth factor receptor (EGFR, erbB1) is overexpressed in primary breast cancer and in some reports is a poor prognostic factor. We previously reported that metastatic breast cancer patients with elevated pretreatment serum HER-2/neu have decreased response and survival. (JCO 21: 1967, 2003).,Pretreatment serum EGFR was quantified in the 1 line phase III letrozole-tamoxifen trial and in controls using the Oncogene Science/Bayer Diagnostics EGFR ELISA.,Serum EGFR from 117 healthy post-menopausal female controls measured 64.1 ± 13.3 ng/ml (mean ± SD) (Range 39.5-117.1 ng/ml). Using a cutpoint of 44.1 ng/ml from the control group (5% non-parametric method), 62/542 patients (11%) had decreased serum 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) to 1 line hormone therapy, but did have significantly reduced survival compared to patients with normal serum EGFR levels (median survival 22.8 vs. 30.4 mos.) (P= .006). Combined analysis of pretreatment serum EGFR and HER-2 yielded no additional predictive information for ORR, CBR, TTP, and TTF compared to serum HER-2 alone. However, combined serum EGFR and HER-2 analysis identified a subgroup of patients with decreased serum EGFR and normal serum HER-2 (n = 43/542, 8%) that had significantly reduced survival compared to patients with normal serum levels of both EGFR and HER-2 (median survival 23.5 vs. 37.1 mos.) (P= .007). In multivariate analysis, decreased serum EGFR level remained a significant independent prognostic factor for decreased survival (hazard ratio HR = 1.59, P= .005). Other significant variables for decreased survival included the presence of liver metastasis (HR = 2.31, P <.0001) and elevated serum HER-2 (HR = 1.80, P= <.0001), while positive hormone receptor status lowered the risk of mortality (HR = .78, P= .03).,In metastatic breast cancer patients, decreased serum EGFR/normal serum HER-2 predicted for a shorter survival - similar to elevated serum HER-2. This patient subgroup deserves further study to assess response to anti-EGFR-directed therapies. [Table: see text].