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 language | English (US) |
|---|---|
| Pages (from-to) | 1281-1289 |
| Number of pages | 9 |
| Journal | Clinical Cancer Research |
| Volume | 19 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 1 2013 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84874885959&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874885959&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-12-3029
DO - 10.1158/1078-0432.CCR-12-3029
M3 - Article
C2 - 23340303
AN - SCOPUS:84874885959
VL - 19
SP - 1281
EP - 1289
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 5
ER -