New targeted therapies in breast cancer.

Targeted therapy for breast cancer has existed since 1986, when Beatson published his observations on oophorectomy. In the past 5 years monoclonal antibodies and tyrosine kinase inhibitors have been evaluated in phase I and II clinical trials of breast cancer. Trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA) was the first such agent to be approved by the US Food And Drug Administration, following findings that it improved survival in patients with metastatic breast cancer. Gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE) has little activity as a single agent in unselected patients, but, preclinical data have suggested synergy with tamoxifen and other hormonal agents, as well as other growth factor inhibitors. Bevacizumab (Avastin; Genentech, Inc), a monoclonal antibody against vascular endothelial growth factor is being evaluated in metastatic breast cancer. Furthermore, agents targeting other pathways, such as the Ras pathway with farnesyl transferase inhibitors, and mTOR with rapamycin analogues are currently under investigation. In the next few years, and as trials with the above agents mature, we will further define the role of these targeted agents in the treatment of breast cancer.