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

Bryan P. Schneider, Robert J. Gray, Milan Radovich, Fei Shen, Gail Vance, Lang Li, Guanglong Jiang, Kathy D. Miller, Julie R. Gralow, Maura N. Dickler, Melody A. Cobleigh, Edith A. Perez, Tamara N. Shenkier, Kirsten Vang Nielsen, Sven Müller, Ann Thor, George W. Sledge, Joseph A. Sparano, Nancy E. Davidson, Sunil S. Badve

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1281-1289
Number of pages9
JournalClinical Cancer Research
Volume19
Issue number5
DOIs
StatePublished - Mar 1 2013

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Gene Amplification
Paclitaxel
Vascular Endothelial Growth Factor A
Breast Neoplasms
Survival
Neoplasms
Progesterone Receptors
Estrogen Receptors
Multivariate Analysis
Triple Negative Breast Neoplasms
Bevacizumab
Paraffin
Disease-Free Survival
Single Nucleotide Polymorphism
Research Design
Biomarkers
Hormones

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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. / Schneider, Bryan P.; Gray, Robert J.; Radovich, Milan; Shen, Fei; Vance, Gail; Li, Lang; Jiang, Guanglong; Miller, Kathy D.; Gralow, Julie R.; Dickler, Maura N.; Cobleigh, Melody A.; Perez, Edith A.; Shenkier, Tamara N.; Nielsen, Kirsten Vang; Müller, Sven; Thor, Ann; Sledge, George W.; Sparano, Joseph A.; Davidson, Nancy E.; Badve, Sunil S.

In: Clinical Cancer Research, Vol. 19, No. 5, 01.03.2013, p. 1281-1289.

Research output: Contribution to journalArticle

Schneider, BP, Gray, RJ, Radovich, M, Shen, F, Vance, G, Li, L, Jiang, G, Miller, KD, Gralow, JR, Dickler, MN, Cobleigh, MA, Perez, EA, Shenkier, TN, Nielsen, KV, Müller, S, Thor, A, Sledge, GW, Sparano, JA, Davidson, NE & Badve, SS 2013, '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', Clinical Cancer Research, vol. 19, no. 5, pp. 1281-1289. https://doi.org/10.1158/1078-0432.CCR-12-3029
Schneider, Bryan P. ; Gray, Robert J. ; Radovich, Milan ; Shen, Fei ; Vance, Gail ; Li, Lang ; Jiang, Guanglong ; Miller, Kathy D. ; Gralow, Julie R. ; Dickler, Maura N. ; Cobleigh, Melody A. ; Perez, Edith A. ; Shenkier, Tamara N. ; Nielsen, Kirsten Vang ; Müller, Sven ; Thor, Ann ; Sledge, George W. ; Sparano, Joseph A. ; Davidson, Nancy E. ; Badve, Sunil S. / 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. In: Clinical Cancer Research. 2013 ; Vol. 19, No. 5. pp. 1281-1289.
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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.",
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T1 - 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

AU - Schneider, Bryan P.

AU - Gray, Robert J.

AU - Radovich, Milan

AU - Shen, Fei

AU - Vance, Gail

AU - Li, Lang

AU - Jiang, Guanglong

AU - Miller, Kathy D.

AU - Gralow, Julie R.

AU - Dickler, Maura N.

AU - Cobleigh, Melody A.

AU - Perez, Edith A.

AU - Shenkier, Tamara N.

AU - Nielsen, Kirsten Vang

AU - Müller, Sven

AU - Thor, Ann

AU - Sledge, George W.

AU - Sparano, Joseph A.

AU - Davidson, Nancy E.

AU - Badve, Sunil S.

PY - 2013/3/1

Y1 - 2013/3/1

N2 - 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.

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