The Role of Angiogenesis in Breast Cancer Progression

Increasingly abundant evidence indicates that the ability of a tumor to command angiogenesis is an important determinant of its phenotype. The data that support this viewpoint were first gained in patients with carcinoma of the breast (Weidner et al, 1991), and confirmatory data have subsequently been obtained in studies conducted in breast and many other solid tumors (see Chapter 4). Additionally, the discovery of various proangiogenic and antiangiogenic molecules has led to the viewpoint that in the normally quiescent vasculature of an adult, the effects of angiogenesis inhibitors predominate for endothelial cells. Therefore, it follows that in angiogenic tumors, the balance between inhibition and stimulation of angiogenesis is disrupted so that endothelial stimulation is favored. Much effort has been directed toward identifying particular angiogenesis stimulators or inhibitors important in neoangiogenesis of breast cancer. Although a multiplicity of candidate stimulators and inhibitors have been investigated, and although vascular endothelial growth factor (VEGF) has been correlated with poor prognosis in breast cancer (Toi et al, 1995a; Gasparini et al, 1997; Relf et al, 1997; Eppenberger et al, 1998), it is becoming clear that we will probably not find any single angiogenic molecule that is responsible for the neovascularization of this disease. It appears more likely that tumors can influence expression of a large number of angiogenesis stimulators and inhibitors, and that this influence extends to molecules expressed by stromal cells as well as those expressed by the tumor cells themselves (reviewed in Pluda, 1997).