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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.

SUBMITTER: Schneider BP 

PROVIDER: S-EPMC3594423 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Publications

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.

Schneider Bryan P BP   Gray Robert J RJ   Radovich Milan M   Shen Fei F   Vance Gail G   Li Lang L   Jiang Guanglong G   Miller Kathy D KD   Gralow Julie R JR   Dickler Maura N MN   Cobleigh Melody A MA   Perez Edith A EA   Shenkier Tamara N TN   Vang Nielsen Kirsten K   Müller Sven S   Thor Ann A   Sledge George W GW   Sparano Joseph A JA   Davidson Nancy E NE   Badve Sunil S SS  

Clinical cancer research : an official journal of the American Association for Cancer Research 20130122 5


<h4>Purpose</h4>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.<h4>Experimental design</h4>E2100 was a phase III trial comparing paclitaxel with or without bevacizumab for patients with metastatic breast cancer. FISH to assess gene amplification  ...[more]

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