The clinical significance of epidermal growth factor receptor (EGF-R) in human breast cancer: a review on 5232 patients.

EGF-R positivity was shown to be present in 2500 (48%) of 5232 breast tumors in 40 different series of patients. The mean of the percentages of EGF-R positivity in the individual series reported by these 40 different groups of investigators is 45% (range 14-91%). Overall there are generally no clear differences between results obtained by radioligand binding assays, immunological methods, autoradiography, and measurement of EGF-R transcripts although the mean percentage of EGF-R-positive tumors determined by immunological methods tends to be somewhat lower. Nearly all studies indicate a negative relationship between EGF-R and steroid receptor status (28 of 31 studies for ER, 12/19 for PR) showing that EGF-R positivity is twice as high in ER or PR- negative tumors compared to ER or PR- positive tumors (approximately 50-60% vs. 30%). With regard to other prognostic factors the majority of investigators (10/18) also reported a significant (positive) correlation with tumor grade, but only a minority found a significant relationship between EGF-R status and patient age (2/9), menopausal status (1/7), histological type (3/7), tumor size (2/17), nodal status (5-9/20), ploidy (1/7), or proliferation indices (3/9). No relationship was observed with tumor insulin-like growth factor I receptor, PRL receptor (PRL-R), and LHRH receptor (LHRH-R) status, but an inverse relationship between EGF-R and somatostatin receptor may be present. However, it has to be stressed that the series in which the relationship between EGF-R status and other prognostic factors were investigated, contained relatively few patients (mostly less than 100). Therefore, when larger groups of patients are investigated, more significant relationships may be observed, especially with respect to nodal status, tumor ploidy, and proliferation indices. In fact, we calculated the presence of EGF-R positivity overall in 35% of 253 aneuploid tumors vs. in only 15% of 114 diploid tumors (P less than 0.0001). In addition most studies observed a trend, if no significant correlation, between higher EGF-R levels in tumors with the highest percentages of S-phase or Ki-67 expression. With regard to relapse-free and overall survival, five of nine different groups of investigators showed significant prognostic value of EGF-R after short-term (1- to 4-yr) follow-up, indicating that patients with EGF-R-positive tumors have a poor prognosis. However, three of five groups with a maximal follow-up of at least 6 yr found only a tendency for any relationship between EGF-R status and long-term outcome.