Trastuzumab (Herceptin) in the treatment of breast cancer with HER2 overexpression

HER2 is a 185 kDa transmembrane receptor with tyrosine kinase activity encoded by the HER2/neu gene. HER2 is overexpressed in 25%–30% of breast cancer and confers an agressive clinic course. Trastuzumab (Herceptin) is a monoclonal antibody directed against HER2 receptor that has a favorable toxicity profile and produces responses as a single agent in women with metastatic breast cancer with HER2 overexpression. A multicenter phase III trial in HER2 positive metastatic breast cancer, compared first line chemotherapy with adriamycin/cyclophosphamide or paclitaxel alone or the same chemotherapy plus trastuzumab. Response rate, duration of response and time to progression, were better with the combination. Remarkably, overall survival was significantly improved in patients with trastuzumab and chemotherapy. These studies led to the approval of trastuzumab for HER2 positive metastatic breast cancer. Ongoing trials are analyzing new combinations of trastuzumab and chemotherapy or hormonal therapy. The role of trastuzumab in adjuvant and neoadjuvant therapy is also under investigation.