Clinical significance of angiogenic factors in breast cancer

Growth, progression, and metastasis of breast cancer, as well as of most of the other tumors, are angiogenesis-dependent processes. Several pro-angiogenic growth factors and endogenous inhibitors of angiogen esis have been identified and sequenced, and experimental studies suggest t hat angiogenic activity of a tumor may result from downregulation of inhibi tors of angiogenesis or up-regulation of endothelial growth factors. The me chanisms leading to the alteration of the balance between positive and nega tive modulators of angiogenesis are only partially known. We are at the beginning of research to identify the more active angiogenic factors in human breast cancer, and little information is presently availab le on their clinical significance. Preliminary results suggest that among t he known angiogenic peptides, both vascular endothelial growth factor (VEGF ) and platelet-derived endothelial cell growth factor/ thymidine phosphoryl ase (PD-ECGF/TP) have promising prognostic and, perhaps, predictive value. No data are available on the clinical value of co-determination of positive and negative regulators of angiogenesis to look at the angiogenic balance of each single tumor. Only a few studies have assessed the role of endogeno us inhibitors of angiogenesis in human breast cancer, with results availabl e only on thrombospondin-1 and -2 (TSP-1, -2). Finally, the determination of some integrins such as alpha 6 and alpha(v)be ta(3) and of some other endothelial-adhesion molecules seems to be of poten tial prognostic value. Recognizing which are the more biologically active positive and negative an giogenic factors is the key for the identification not only of new prognost ic markers but also of targets for antiangiogenic therapy in human breast c ancer.