Association of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor-2 Genetic Polymorphisms With Outcome in a Trial of Paclitaxel Compared With Paclitaxel Plus Bevacizumab in Advanced Breast Cancer: ECOG 2100

摘要: Purpose No biomarkers have been identified to predict outcome with the use of an antiangiogenesis agent for cancer. Vascular endothelial growth factor (VEGF) genetic variability has associated altered risk breast cancer and variable promoter activity. Therefore, we evaluated association VEGF genotype efficacy toxicity in E2100, a phase III study comparing paclitaxel versus plus bevacizumab as initial chemotherapy metastatic Patients Methods DNA was extracted from tumor blocks patients E2100. Three hundred sixty-three samples were available evaluate associations between outcome. Genotyping performed selected polymorphisms receptor 2. Testing each polymorphism performed. Results The VEGF-2578 AA superior median overall survival (OS) combination arm when compared alternate genotypes combined (hazard ratio 0.58; 95% CI, 0.36 0.93; P .023). VEGF-1154 A allele also demonstrated OS additive effect active but not control 0.62; 0.46 0.83; .001). Two additional genotypes, VEGF-634 CC VEGF-1498 TT, significantly less grade 3 or 4 hypertension (P .005 .022, respectively).