Breast cancer is the most commonly diagnosed cancer in women and one of the earliest tumor types for which we have used molecular characterization of the tumor to guide treatment. Approximately one quarter of breast tumors show overexpression of HER2, a transmembrane receptor tyrosine kinase. This review focuses on the HER2 pathway and consequences of overexpression, or activation, of this signal. Trastuzumab, the first line monoclonal antibody directed at HER2 will also be described in terms of mechanism of action and influence on patient care. Additional focus will be paid to understanding mechanisms of primary and secondary resistance to the agent. We then attempt to describe the current milieu of therapeutic options for patients resistant or refractory to trastuzumab. There are certainly many new targeted agents as well as exciting preclinical data which may offer some direction for treatment of patients in whom trastuzumab is not an effective targeted agent.
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