The epidermal growth factor receptor as a prognostic marker: Results of 370 patients and review of 3009 patients

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Abstract
Epidermal growth factor receptor (EGFR) and estrogen receptor (ER) were assayed by ligand binding in tumors from 370 patients with primary breast carcinoma with a median follow up of 18 months. Forty seven percent (175/370) and 57% (210/370) of tumors had >20 fmol/mg and >10 fmol/mg of EGFR and ER respectively. There was a highly significant inverse relationship between EGFR and ER (p=0.0032). There was also a significant association between EGFR and patient age (p=0.0006) but no correlation between EGFR and lymph node status, tumor grade, or tumor size (p=0.104, p=0.198, and p=0.085 respectively). In a univariate analysis of all patients, EGFR expression was not associated with a significant reduction in overall survival (OS). However, there was a significant decrease in relapse-free survival (RFS) and OS in node negative EGFR positive patients (p=0.03 and p=0.05 respectively). In a multivariate analysis (Cox proportional hazard model) of all patients, lymph node status was an independent prognostic indicator for OS and RFS (p<0.00005 and p=0.00005 respectively), ER status for RFS (p=0.0006), and EGFR (in the node negative model) for RFS (p=0.03). When all patients were stratified for EGFR and ER, there was a significant difference in RFS and OS such that EGFR positive and ER negative had the worst prognosis (p=0.0034 and p=0.005 respectively). A similar relationship was observed for OS in node negative patients (p=0.004) and for RFS in node positive patients (p=0.009). In a review of 3009 patients with follow-up, 11/16 series showed high EGFR was associated with shorter RFS or OS in univariate analysis, and 4 showed this in multivariate analysis. However, most series had inadequate follow-up time and most did not include multivariate analysis. This highlights the need for uniform criteria of reporting trials of prognostic factors.