Microvascular Density of Breast Cancer in Bone Metastasis: Influence of Therapy

Abstract

Background: Bone is the most frequent site of systemic progression of breast cancer (BRC). Angiosuppressive therapy has now entered the management of progressing cancers, therefore it is clinically important to obtain information on vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) of bone metastasis of BRC. Materials and Methods: VEGF expression and MVD were evaluated in bone metastases of BRC immunohistochemically in paraffin samples of 18 patients and compared to their primary tumors. MVD was determined by using the hot-spot method and the endothelial marker, CD34. Results: Chemo- and/or endocrine therapy-naïve BRC cases progressed to the bone with a concomitant increase in their angiogenic potential, suggesting that this is the “natural history” of BRC progression. On the other hand, this study revealed that vascularization of the bone metastases of BRC patients that had received adjuvant (chemo- and/or endocrine) therapy was significantly decreased compared to the corresponding primary tumors, also supported by a decreased VEGF expression in metastases, both suggesting that the treatment significantly affected the angiogenic phenotype of the progressing disease. Conclusion: Angiosuppressive therapy is a new approach to cancer management including BRC and is frequently applied in the advanced stage of disease. Tumors with a prominent angiogenic phenotype (high MVD and VEGF) are primary candidates for such regimes. The fact that chemo-endocrine adjuvant therapy of BRC resulted in a weaker angiogenic phenotype in bone metastases compared to non-treated cases may suggest that these latter patients are better candidates for angiosuppressive interventions.