Monoclonal antibodies, small molecules, and vaccines in the treatment of breast cancer.

The human epidermal growth factor receptor (HER, ErbB) family of receptors is considered an important therapeutic target, and various types of molecularly based small molecules, including monoclonal antibodies, protein tyrosine kinase inhibitors, and therapeutic vaccines, are in development as potential therapies for metastatic breast cancer. Trastuzumab (Herceptin; Genentech, Inc.; South San Francisco, CA), the first approved monoclonal antibody for HER-2 (ErbB-2)-overexpressing metastatic breast cancer, provided the proof of principle that targeting specific receptors results in clinical benefit. Other monoclonal antibodies and the small molecule dual protein tyrosine kinase inhibitors show great promise as treatments for metastatic breast cancer but require evaluation in clinical trials to assess their benefits. Therapeutic vaccines may have a role, particularly in early-stage disease, but they are associated with greater limitations and study design issues that make their evaluation difficult. Optimum combination therapy regimens with a variety of novel approaches that incorporate small molecule targeted therapies need to be developed, and the population most likely to benefit from targeted therapies needs to be identified.