Herceptin in the treatment of metastatic breast cancer

Abstract

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 early-stage breast cancers and is associated with a poor clinical outcome. Antibodies to the HER2 receptor have a cytostatic effect by suppressing growth of HER2 overexpressing tumor cells. The humanized antibody rhuMAb4D5 (Herceptin), which has recently been approved by the U. S. Food and Drug Administration for the treatment of metastatic breast cancer, has been shown to improve 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 demonstrate a therapeutic advantage in the administration of Herceptin in combination with chemotherapeutic agents. In a multicenter clinical trial for patients with HER2/neu-overexpressing metastatic breast cancer the use of Herceptin in combination with doxorubicin/cyclophosphamide or paclitaxel resulted in significantly improved objective clinical responses and prolongation of survival. We report on recent studies with Herceptin as a single agent and in combination with chemotherapy. Mechanisms of action of Herceptin are presented. Diagnosic issues in determining HER2 overexpression are discussed. At present Herceptin has only been approved in North America. In conclusion, guidelines for Germany for the treatment of HER2-positive metastatic breast cancer are given.