Drug therapy: Trastuzumab - Mechanism of action and use in clinical practice

OVEREXPRESSION OF HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR type 2 (HER2, also referred to as HER2/neu or ErbB-2), a 185-kD receptor first described more than two decades ago,1 occurs in 20 to 30% of invasive breast carcinomas. In general, patients with breast-cancer cells that overexpress this receptor or that have a high copy number of its gene have decreased overall survival and may have differential responses to a variety of chemotherapeutic and hormonal agents.2-6 Thus, strategies to target HER2 appear to be important in treating breast cancer. One such medication is trastuzumab (Herceptin, Genentech), a humanized monoclonal antibody. Trastuzumab binds to the extracellular juxtamembrane domain of HER2 and inhibits the proliferation and survival of HER2-dependent tumors. It is approved by the Food and Drug Administration (FDA) for patients with invasive breast cancers that overexpress HER2. This review considers trastuzumab's mechanism of action and its clinical value. Copyright © 2007 Massachusetts Medical Society.