Trial Information

VEGF Gene Amplification/Deletion and Haplotype as Biomarkers for Bevacizumab in Breast Cancer

OBJECTIVES:

Primary

- 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
in ECOG-E2100.

- 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.

Secondary

- 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.