Toward Checkmate: Biology and Breast Cancer Therapy for the New Millennium

A better understanding of the biology of breast cancer should leadto the rational development of new treatments and the ability tocustomize therapy for individual patients. Though promising intheory, translating advances in biological knowledge to the clinichas been difficult. Recently several areas of research haveproduced treatments which have entered clinical trials; three willbe reviewed here. The growth of breast cancer is regulated bygrowth factors and their receptors; amplification or overexpressionis associated with poor prognosis. As such inhibition of growthfactors and/or growth factor receptors may provide an idealtherapeutic target. Herceptin binds to c-erbB-2, a member of theepidermal growth factor receptor family. Significant responses wereseen in patients with c-erbB-2 overexpressing breast cancer withHerceptin administered as a single agent or in combination withchemotherapy. Herceptin was approved by the Food and DrugAdministration in late 1998. Breast cancer invasion and metastasisrequires degradation of the surrounding basement membrane by matrixmetalloproteinases and other proteolytic enzymes. Syntheticinhibitors of these enzymes are now in clinical trials. Breastcancers must stimulate angiogenesis, the growth of new bloodvessels, in order to grow beyond a few millimeters in diameter.This nascent vascular network provides another opportunity fortherapy. Preclinical models support the critical role ofangiogenesis and the therapeutic benefit of angiogenesisinhibition; clinical trials are underway.