Journal of Clinical Oncology · 1998 · 270 citations · 23 references
MedicineOncologyPathologyBreast OncologyMetastasisMolecular OncologyAngiogenesisAngiogenesis In CancerBreast Cancer OncologyMalignant NeoplasmsMolecular Tumor ProfilingEstrogen Receptor ExpressionEstrogen Receptor StatusHistologic GradePrognostic Factors AnalysisPrognostic Value Of GradeTumor Size PrognosisVascular Endothelial Growth FactorVascular Endothelial Growth Factor Receptors
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 VEGF165 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 but positively associated with tumor size and histologic grade. Patients with VEGF levels above the median value (2.40 pg/microg 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.
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Tumor Angiogenesis and Metastasis — Correlation in Invasive Breast Carcinoma
Noel Weidner, Joseph P. Semple, William R. Welch et al. · New England Journal of Medicine · 1991 · 5.7K citations
Medicine, Cancer Biology, Oncology +15
Keith A. Houck, Napoleone Ferrara, Jane Winer et al. · Molecular Endocrinology · 1991 · 1.4K citations · Full text
J E Park, G A Keller, Napoleone Ferrara · Molecular Biology of the Cell · 1993 · 1.1K citations · Full text