Trastuzumab: targeted therapy for the management of HER-2/neu-overexpressing metastatic breast cancer.

Breast cancers are a biologically heterogeneous group of mammary tumors with distinct natural histories and varied responses to established therapies. They have long been divided into those that are hormone sensitive [as defined by expression of the estrogen receptor alpha (ERalpha) and/or the progesterone receptor (PR)] and those that are not. Notably, only those breast cancers that express ERalpha and/or PR typically respond to hormonal therapy with tamoxifen, aromatase inhibitors, or the newer agent fulvestrant. More recently, the transmembrane tyrosine kinase receptor HER-2/neu was identified as an oncogene overexpressed by about 30% of breast cancers. These HER-2/neu-overexpressing breast cancers define a subset of breast tumors that are characteristically more aggressive, and women who develop them have a shorter survival. Trastuzumab (Herceptin), a humanized monoclonal antibody specific for HER-2/neu, has revolutionized the management of metastatic HER-2/neu-overexpressing breast cancers. As a single agent, it produces response rates similar to those of many single-agent chemotherapeutic agents active in metastatic breast cancer and has limited toxicity. Combining trastuzumab with chemotherapy can result in synergistic antitumor activity. The clear efficacy of trastuzumab against HER-2/neu-overexpressing metastatic breast cancer has led to a keen interest in testing its role in the management of early breast cancer, and multiple large clinical trials are currently in progress. This review summarizes the available clinical data on the use of trastuzumab in HER-neu-overexpressing breast cancer and briefly highlights emerging opportunities for innovative, trastuzumab-based breast cancer therapies.