Clinical significance of determination of surrogate markers of angiogenesis in breast cancer

Compelling experimental and clinical data support the concept that breast carcinoma, as most of the ether solid tumors, needs to develop the angiogenic phenotype for invasiveness, progression and metastasis. Several studies have determined intratumoral microvessel density by panendothelial markers and immunohistochemical techniques, with most of them showing that the degree of vascularity is associated with prognosis of the patients operated of early-stage invasive breast cancer. More recently, certain angiogenic peptides have been assessed in human breast cancer: vascular endothelial growth factor (VEGF), platelet derived-endothelial cell growth factor (PD-ECGF, also known as thymidine phosphorylase, TP) and fibroblast growth factor family (FGFs). Among these, the most studied is VEGF, which appears to be a powerful prognostic indicator. Little data are available on the clinical significance of naturally occurring antiangiogenic factors, with few studies reporting on interleukin-12 and thrombospondins. In vivo techniques for dynamic assessment of tumor blood network are presently under extensive research, in particular for monitoring activity of inhibitors of angiogenesis. The methods of assessment of angiogenic activity and the results of published clinical studies in peer reviewed Journals with a computerized overview of literature will be presented. Overall, the results of the reported studies suggest that human breast cancer is an angiogenic-dependent tumor for which antiangiogenic therapy represents a promising novel antitumoral therapeutic strategy. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.