Herceptin in the treatment of metastatic breast cancer

Amplification of the HER-2/neu (c-erbB-2) gene, resulting in overexpression of the p185HER-2 growth factor, receptor occurs in approximately 25% of ea rly-stage breast cancers and is associated with a poor clinical outcome. An tibodies to the HER2 receptor have a cytostatic effect by suppressing growt h of HER2 overexpressing tumor cells. The humanized antibody rhuMAb4D5 (Her ceptin), which has recently been approved by the U.S. Food and Drug Adminis tration for the treatment of metastatic breast cancer, has been shown to im prove the response rate, response duration to chemotherapy and to extend 12 -month overall survival in HER2-amplified breast cancers. The response rate to Herceptin given as a single agent is a modest 23%. Preclinical data dem onstrate a therapeutic advantage in the administration of Herceptin in comb ination with chemotherapeutic agents. In a multicenter clinical trial for p atients with HER2/neu-overexpressing metastatic breast cancer the use of He rceptin in combination with doxorubicin/ cyclophosphamide or paclitaxel res ulted in significantly improved objective clinical responses and prolongati on of survival. We report on recent studies with Herceptin as a single agen t and in combination with chemotherapy. Mechanisms of action of Herceptin a re presented. Diagnosic issues in determining HER2 overexpression are discu ssed. At present Herceptin has only been approved in North America. In conc lusion, guidelines for Germany for the treatment of HER2-positive metastati c breast cancer are given.