Prognostic and predictive value of tumor vascular endothelial growth factor gene amplification in metastatic breast cancer treated with paclitaxel with and without bevacizumab; results from ECOG 2100 trial Journal Article
| Authors: | Schneider, B. P.; Gray, R. J.; Radovich, M.; Shen, F.; Vance, G.; Li, L.; Jiang, G.; Miller, K. D.; Gralow, J. R.; Dickler, M. N.; Cobleigh, M. A.; Perez, E. A.; Shenkier, T. N.; Nielsen, K. V.; Müller, S.; Thor, A.; Sledge, G. W. Jr; Sparano, J. A.; Davidson, N. E.; Badve, S. S. |
| Article Title: | Prognostic and predictive value of tumor vascular endothelial growth factor gene amplification in metastatic breast cancer treated with paclitaxel with and without bevacizumab; results from ECOG 2100 trial |
| Abstract: | Purpose: Clinically validated biomarkers for anti-angiogenesis agents are not available. We have previously reported associations between candidate VEGFA single-nucleotide polymorphisms (SNP) and overall survival (OS) in E2100. The associations between tumor VEGFA amplification and outcome are evaluated here. Experimental Design: E2100 was a phase III trial comparing paclitaxel with or without bevacizumab for patients with metastatic breast cancer. FISH to assess gene amplification status for VEGFA was conducted on paraffin-embedded tumors from 363 patients in E2100. Evaluation for association between amplification status and outcomes was conducted. Results: Estrogen receptor (ER)+ or progesterone receptor (PR)+ tumors were less likely to have VEGFA amplification than ER/PR- tumors (P = 0.020). VEGFA amplification was associated with worse OS (20.2 vs. 25.3 months; P = 0.013) in univariate analysis with a trend for worse OS in multivariate analysis (P = 0.08). There was a significant interaction between VEGFA amplification, hormone receptor status, and study arm. Patients with VEGFA amplification and triple-negative breast cancers (TNBC) or HER2 amplification had inferior OS (P = 0.047); amplification did not affect OS for those who were ER+ or PR+ and HER2-. Those who received bevacizumab with VEGFA amplification had inferior progression-free survival (PFS; P= 0.010) and OS (P = 0.042); no association was seen in the control arm. Test for interaction between study arm and VEGFA amplification with OS was not significant. Conclusion: VEGFA amplification in univariate analysis was associated with poor outcomes; this was particularly prominent in HER2+ or TNBCs. Additional studies are necessary to confirm the trend for poor OS seen on multivariate analysis for patients treated with bevacizumab. © 2012 American Association for Cancer Research. |
| Keywords: | adult; controlled study; human tissue; treatment outcome; aged; aged, 80 and over; middle aged; vascular endothelial growth factor a; survival rate; retrospective studies; human cell; major clinical study; overall survival; bevacizumab; paclitaxel; follow-up studies; neoplasm staging; in situ hybridization, fluorescence; progression free survival; gene amplification; protein protein interaction; randomized controlled trial; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor 2; genetic association; breast neoplasms; fluorescence in situ hybridization; vasculotropin a; neoplasm metastasis; tissue array analysis; receptor, erbb-2; receptors, estrogen; receptors, progesterone; phase 3 clinical trial; estrogen receptor; progesterone receptor; hormone receptor; breast metastasis; predictive value; paraffin; triple negative breast cancer; antibodies, monoclonal, humanized |
| Journal Title: | Clinical Cancer Research |
| Volume: | 19 |
| Issue: | 5 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2013-03-01 |
| Start Page: | 1281 |
| End Page: | 1289 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-12-3029 |
| PROVIDER: | scopus |
| PMCID: | PMC3594423 |
| PUBMED: | 23340303 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 April 2013" - "CODEN: CCREF" - "Source: Scopus" |
