VEGF Gene Amplification/Deletion and Haplotype as Biomarkers for Bevacizumab in Breast Cancer
- To demonstrate that vascular endothelial growth factor-A (VEGFA) haplotypes that are
associated with an increased VEGFA expression will predict superior outcome for
patients with metastatic breast cancer receiving bevacizumab in ECOG-E2100 (but not for
the control arm).
- To demonstrate that candidate single nucleotide polymorphisms (SNPs) will further
improve the predictive capacity of outcome (efficacy and toxicity) in patients enrolled
- To demonstrate that tumor VEGFA amplification or borderline amplification (estimated
14% frequency) will predict superior outcome for patients with metastatic breast cancer
receiving bevacizumab on ECOG-E2100 whereas those with VEGFA deletion (estimated 11%
frequency) will predict inferior outcome.
- To demonstrate that VEGFA amplification/deletion will not predict outcome in the
control arm of ECOG-E2100.
- To demonstrate that tumor VEGFA amplification will predict increased protein expression
as ascertained by IHC.
- To demonstrate that a combined algorithm calculated from tumor-specific variability
(VEGFA amplification/deletion) and host-specific variability (SNPs) will optimally
predict outcome (efficacy) with bevacizumab in patients enrolled on ECOG-E2100.
OUTLINE: This is a multicenter study.
Previously collected tumor-derived DNA is analyzed for VEGFA amplification/deletion and
haplotype as biomarkers for outcome after bevacizumab treatment. Gene expression,
polymorphism, protein expression analysis, and IHC are performed on the samples.
Comparison between VEGF haplotype and median overall survival (OS) and grade 3/4 hypertension (HTN)
Bryan P. Schneider, MD
Indiana University Melvin and Bren Simon Cancer Center