Prognostic analysis of tumour angiogenesis, determined by microvessel density and expression of vascular endothelial growth factor, in high-risk primary breast cancer patients treated with high-dose chemotherapy

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Abstract
In contrast to early breast cancer, the prognostic effect of tumour angiogenesis in tumours with advanced axillary spread has been less studied. We retrospectively analysed the effect of microvessel density (MVD) and vascular endothelial growth factor (VEGF) by immunohistochemistry on the outcome of 215 patients treated uniformly within prospective trials of high-dose chemotherapy for 4–9 and 10 positive nodes, and followed for a median of 9 (range 3–13) years. Microvessel density was associated with epidermal growth factor receptor (EGFR) expression (PP=0.001). Vascular endothelial growth factor overexpression (51% of patients) was associated with overexpression of EGFR (P=0.01) and HER2 (PP=0.3). High MVD was associated with worse relapse-free survival (74 vs 44%, Pvs 44%, P<0.001). Vascular endothelial growth factor overexpression had no effect on outcome. Multivariate analyses showed a prognostic effect of MVD independently of other known prognostic factors in this patient population. In conclusion, tumour angiogenesis, expressed as MVD, is a major independent prognostic factor in breast cancer patients with extensive axillary involvement.

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