Antibody therapy for early-stage breast cancer: trastuzumab adjuvant and neoadjuvant trials

The HER2/neu gene is amplified in approximately 25% of breast cancers; amplification is associated with an aggressive course. Her2/neu activation initiates signalling cascades that result in proliferation, angiogenesis and survival of breast cancer cells. Trastuzumab is a monoclonal antibody against Her2. Binding of the antibody activates an immune response and decreases Her2 phosphorylation, phosphatidylinositol 3-kinase (PI3K)/Akt activity and vascular endothelial growth factor levels. When trastuzumab is used preoperatively, apoptosis is seen in resected tumours. In the adjuvant setting, large, randomised trials demonstrate improved outcome for trastuzumab with chemotherapy followed by a year of trastuzumab. In a combined analysis of two such studies, overall survival was improved (hazard ratio for death 0.67, p = 0.015). The agent has associated cardiotoxicity. Trastuzumab is a highly active agent in Her2-overexpressing breast cancer.