Properties of EGF-Receptor Family Proteins And Their Role In The Management Of Breast Cancer. Michael D. Taylor and James L. Wittliff, Brown Cancer Center, University of Louisville, Louisville, Ky. 40202.

A human proto-oncogene called HER-2/neu (c-erb B2), originally isolated from rat neuroblastomas, encodes a 185 kDa surface glycoprotein with tyrosine kinase activity. The protein product of the gene, mapped to chromosome 17 at q21, exhibits 50% sequence homology with the EGF receptor protein including the transmembrane domain. Other members of the EGF receptor family, called erb B3 (HER-3) and erb B4 (HER-4), have been identified recently. Although a number of neu-specific activating factors have been reported, the identity of the native ligand is unclear. Amplification of the c-erb B2 gene has been determined in several types of cancers including breast carcinomas where it was correlated with early relapse and decreased overall survival. Gene copy number appeared to be weakly related to levels of c-erb B2 oncoprotein in cancer biopsies, and the gene amplification assays were too complex to be practical for the routine clinical laboratory. Several EIA, ELISA and immunohistochemical methods were developed for detection of the oncoprotein in tissue and serum samples. Although many studies with these methods have demonstrated a relationship between increased c-erb B2 oncoprotein expression and decreased disease-free and overall survival in breast cancer, results in other published reports were not in agreement. As a consequence, the Guidelines of the American Society of Clinical Oncology concluded there was insufficient data in 1996 to warrant the use of c-erb B2 in breast cancer management. Recently, however, the FDA approved a gene-based test for monitoring breast cancer progression. Collectively, these studies and the Standards of Laboratory Practice on Guidelines for the Use of Tumor Markers in the Diagnosis and Management of Cancer indicate a need for quality assurance specimens and proficiency programs for this analyte to evaluate its efficacy in randomized clinical trials such as those conducted by cooperative groups.