Vascular endothelial growth factor is of high prognostic value in node-negative breast carcinoma

Purpose: The prognostic value of vascular endothelial growth factor (VEGF) protein, known to stimulate endothelial growth and angiogenesis, was evaluated in node-negative breast carcinoma (NNBC) and compared with established prognostic factors. Patients and Methods: In 525 consecutive patients with primary invasive NNBC (T1-2N0M0; tumor, node, metastasis stage), of whom 500 patients did not receive any systemic therapy, the cytosolic levels of VEGF(165) were measured by using a quantitative enzyme-linked immunosorbent assay The median follow-up was 46 months. Univariate and multivariate analyses were performed. Results: VEGF level was significantly inversely correlated with estrogen receptor (ER) positivity bur positively associated with tumor size and histologic grade. Patients with VEGF levels above the median value (2.40 pg/mu g of DNA) showed a significantly shorter survival time (P = .0012) than patients with levels less than the median value, also when analyzed as a continuous variable (P = .0277). Tumor size, grade, and ER expression were all statistically significant for overall survival in univariate analyses (P = .0069, P = .014, and P < .001, respectively). Multivariate analysis showed that VEGF level was the strongest predictor of overall survival (P = .0199). Histologic grade was also an independent predictor of survival (P = .0477). Among the 381 patients with ER-positive tumors, a group in general considered to have a good prognosis, we found a significant reduction in survival for those with levels of VEGF greater than the median value (P = .0009). Conclusion: The results suggest that the level of VEGF165 protein is an independent, strong prognostic factor for survival in patients with NNBC, especially in the subgroup of patients with ER positivity. Thus, cytosolic VEGF165 might be useful to select patients for adjuvant systemic therapy. J Clin Oncol 16:3121-3128. (C) 1998 by American Society of Clinical Oncology.