HER-2 expression may have predictive value regarding response to therapeutic interventions in breast cancer. A number of reports describe the interaction of HER-2 overexpression and tamoxifen, but data are inconclusive. Chemotherapy trials have supported an interaction between HER-2 overexpression and chemotherapy sensitivity (cyclophosphamide/methotrexate/5-fluorouracil resistance and doxorubicin sensitivity) which is compelling. More recently, HER-2 has been the target for Food and Drug Administration-approved antibody therapy, trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA). The Clinical Trials Assay, a scoring system for tumor material, has been used successfully in the trastuzumab clinical development program. As many of the early studies evaluating the role of HER-2 were retrospective, controlled prospective studies are needed to best determine the value of trastuzumab in the adjuvant clinical setting.