Role of trastuzumab in the adjuvant treatment of HER2-positive early breast cancer

Abstract

Amplification of the human epidermal growth factor receptor 2 (HER2) gene occurs in 18-23% of invasive breast carcinomas and is associated with a worse prognosis. This novel transforming gene was identified in 1985, and in 1987 HER2 amplification was demonstrated to be central to the aggressive, malignant phenotype of these cancers and a significant predictor of both time to relapse and overall survival. These observations led to the development of the first monoclonal antibody targeting the extracellular domain of HER2, trastuzumab (Herceptin®, Genentech and Hoffman LaRoche, Switzerland), which was approved by the US FDA for metastatic breast cancer in 1998. In 2005, results from four major trastuzumab adjuvant trials demonstrated a marked reduction in risk of recurrence, and trastuzumab is now an essential component of the adjuvant treatment of HER2-positive early breast cancer. Concerns regarding cardiac safety and mechanisms of resistance to trastuzumab remain important issues and are being addressed in ongoing research efforts. © 2009 Future Medicine Ltd.