Toward checkmate: biology and breast cancer therapy for the new millennium.

A better understanding of the biology of breast cancer should lead to the rational development of new treatments and the ability to customize therapy for individual patients. Though promising in theory, translating advances in biological knowledge to the clinic has been difficult. Recently several areas of research have produced treatments which have entered clinical trials: three will be reviewed here. The growth of breast cancer is regulated by growth factors and their receptors; amplification or overexpression is associated with poor prognosis. As such inhibition of growth factors and/or growth factor receptors may provide an ideal therapeutic target. Herceptin binds to c-erbB-2, a member of the epidermal growth factor receptor family. Significant responses were seen in patients with c-erbB-2 overexpressing breast cancer with Herceptin administered as a single agent or in combination with chemotherapy. Herceptin was approved by the Food and Drug Administration in late 1998. Breast cancer invasion and metastasis requires degradation of the surrounding basement membrane by matrix metalloproteinases and other proteolytic enzymes. Synthetic inhibitors of these enzymes are now in clinical trials. Breast cancers must stimulate angiogenesis, the growth of new blood vessels, in order to grow beyond a few millimeters in diameter. This nascent vascular network provides another opportunity for therapy. Preclinical models support the critical role of angiogenesis and the therapeutic benefit of angiogenesis inhibition; clinical trials are underway.