Trastuzumab-based combinations in metastatic breast cancer: how to make a choice

Trastuzumab, a humanized monoclonal anti-human epidermal growth factor receptor-2 (HER2) antibody that has proven efficacy as monotherapy in HER2-overexpressing breast cancer, has a favorable toxicity profile characterized by infrequent infusion reactions and a slightly increased incidence of cardiac dysfunction. Regimens that combine trastuzumab with a cytotoxic agent can increase the overall response rate and prolong survival in patients with metastatic breast cancer. Trastuzumab has been investigated in combination with anthracyclines, taxanes, platinum salts, vinorelbine, gemcitabine, capecitabine, and combinations of these agents. Combining trastuzumab with these agents enhances the toxicity of treatment and can especially enhance the risk of cardiotoxicity. This article summarizes data on trastuzumab-based combinations with particular attention to the risk benefit ratio of these therapies. HER2 testing by immunohistochemistry or fluorescence in situ hybridization is discussed in the context of determining the optimal course of treatment for patients.