Implications of the new biology for therapy in breast cancer.

It is a truism that a better understanding of the biology of breast cancer should lead to improvements in diagnosis and therapy. Despite this, our significantly improved grasp of breast cancer biology has had little direct therapeutic impact to date. The technologies used to treat breast cancer (surgery, radiation therapy, chemotherapy, and hormonal therapy) were in general developed decades ago. With the exception of the prognostic factor area, advances in biological knowledge have not translated into either new therapies or altered outcomes. Fortunately, this now appears to be changing. This paper will focus on three emerging areas in which the new biology is most likely to have a therapeutic impact. The first area involves growth factors and their receptors. It is now clear that the growth of breast cancer is regulated by growth factor receptors (eg, EGFR and Her-2/neu), and that their upregulation is associated with impaired prognosis. Growth factors and their receptors represent a promising therapeutic target, both alone and in combination with other standard agents. Recent evidence suggests that growth factors and their receptors may be important for regulating programmed cell death (apoptosis) in breast cancer. A second emerging area involves matrix metalloproteinases. Breast cancer invasion and metastasis involves and requires activation of enzymes capable of dissolving natural barriers to spread. The most heavily studied of these are the matrix metalloproteinases, for which considerable in vitro and in vivo evidence suggests an important role in breast cancer. The recent advent of compounds with matrix metalloproteinase inhibitory activity makes a therapeutic intervention against matrix metalloproteinases appear reasonable. In vivo laboratory evidence suggests that their use may occur in the very near future. A third emerging area revolves around the question of neoangiogenesis (new blood vessel formation) in breast cancer. Breast cancers (indeed, all solid tumors) are incapable of growth beyond a certain critical diameter without new blood vessel formation. Recent work has demonstrated that breast cancers produce angiogenic factors stimulating this new growth. Therapies aimed at blocking this stimulation, and preventing neovascularization represent a promising therapeutic target. Numerous agents capable of preventing new blood vessel formation have been discovered in the laboratory and are poised to enter clinical trials.