Trastuzumab in the management of early and advanced stage breast cancer

Trastuzumab is a monoclonal humanized antibody that has revolutionized the treatment of patients with Her2-positive breast cancer. Already well established in advanced stage disease, the substance was recently introduced in the adjuvant setting, reducing disease recurrences by more than 50% and mortality by approximately one third. Trastuzumab is a rationally designed substance which binds to cancer cells expressing the targeted antigen, and, by different mechanisms, causes tumor cell degradation. However, only one third of patients have an initial response to trastuzumab therapy, and the majority of initial responders demonstrate disease progression within 1 year of treatment initiation. It is therefore necessary to gain further insight into mechanisms of resistance, and develop ways to overcome those. In this article, the role of trastuzumab in early and advanced stage breast cancer is reviewed. We discuss current understandings of the specific tumor biology of Her2-positive breast cancer, and review the mechanism of action of trastuzumab. Further, we try to highlight possible mechanisms of resistance.