Measurement of neovascularization is an independent prognosticator of survival in node-negative breast cancer patients with long-term follow-up

We measured neovascularization, epidermal growth factor receptor, and c-erb B-2 expression in a consecutive series of 233 surgically resected axillary lymph node-negative breast cancer patients with a long-term follow-up to de fine the usefulness of these parameters as independent prognostic indicator s of overall survival (OAS), Microvessel count (MVC), as a measure of neova scularization, was determined using a monoclonal antibody against human fac tor VIII-related antigen. The median MVC of 20 (range, 4-76) was used as a cutoff value for discriminating between low and high vascularized tumors. E pidermal growth factor receptor and c-erbB-2 expression were evaluated by i mmunohistochemistry, Tumors were considered positive if > 10% of the cells showed specific membrane staining. OAS curves were estimated by the Kaplan- Meier method, The indepen-dent prognostic effect of each variable was deter mined with the Cox proportional hazards model. High MVC (P = 0.04), high nu clear grade (P = 0.005), and high S-phase (P = 0.02) significantly affected OAS at univariate analysis. In a Cox multivariate analysis, the characteri stics with an independent prognostic effect on OAS were: MVC (relative haza rd, 2.12; 95% confidence interval, 1.18-3.81; P = 0.01) and nuclear grade ( relative hazard, 2.83; 95% confidence interval, 1.12-7.17; P = 0.01), These results demonstrate that quantification of neovascularization adds useful independent prognostic information on survival in node-negative breast canc er patients with long-term follow-up.