1 Targeted Therapy in Breast Cancer: The HER-2/neu Gene and Protein

The HER-2/neu oncogene, a member of the EGFR or erb gene family, encodes a transmembrane tyrosine kinase receptor which has been linked to prognosis and response to therapy with the anti-HER-2 humanized monoclonal antibody, trastuzumab (HerceptinTM, Genentech Corportation, South San Francisco, CA) in patiebnts wityh advanced metastatic breast cancer. HER-2/neu status has also been tested for its ability to predict the response of breast cancer to other therapies including hormonal therapies, topoisomerase inhibitors and anthracyclines. This review includes an analysis of 80 published studies encompassing more than 25,000 patients to designed to consider the relative advantages and disadvantages of the various methods of measuring HER-2/neu in clicnical breast cancer specimens. Southern blotting, polymerase chain reaction (PCR) amplification detection and fluorescence in situ hybridization (FISH) assays designed to detect HER-2/neu gene amplification are compared with HER-2/neu protein overexpression assays performed by immunohistochemical techniques applied to frozen and paraffin embedded tissues an