Trastuzumab in the Treatment of Breast Cancer – New Developments

Rarely a new drug has influenced the current concept of up-to-date systemic treatment in breast cancer like trastuzumab since the identification of the human epidermal growth factor receptor 2 and its implementation as strong prognostic as well as predictive factor. In human breast cancer, amplification of the HER-2/neu gene results in protein overexpression and poor prognosis. Patients whose tumors have HER-2/neu gene amplification have a shorter disease-free survival time than patients whose tumors exhibit a normal HER-2/neu gene copy number. HER-2/neu gene amplification identifies a biologically unique subset of aggressive breast tumors that are sensitive to growth inhibition and apoptosis induced by anti-HER-2/neu-targeted therapies. Trastuzumab therapy prolongs the survival of patients with metastatic HER-2/neu-overexpressing breast cancer when combined with chemotherapy and has recently been demonstrated to lead to dramatic improvements in disease-free survival when used in the adjuvant therapy setting in combination with or following chemotherapy. Most recent findings are suggesting that trastuzumab might be used in combination with chemotherapy as well as in combination with endocrine treatments, limited to patients presenting with metastatic disease. Still under debate are methods of proper HER-2/neu testing, patient selection, cardiotoxicity, duration of therapy, and directions for future research.