Yang SX, Steinberg SM, Nguyen D, Wu TD, Modrusan Z, Swain SMGene expression profile and angiogenic marker correlates with response to neoadjuvant bevacizumab followed by bevacizumab plus chemotherapy in breast cancer. Clin Cancer Res 14(18): 5893-5899

National Clinical Target Validation Laboratory, Division of Cancer Treatment and Diagnosis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Clinical Cancer Research (Impact Factor: 8.72). 10/2008; 14(18):5893-9. DOI: 10.1158/1078-0432.CCR-07-4762
Source: PubMed


To identify biomarkers and gene expression profile signatures to distinguish patients with partial response (PR) from those with stable disease (SD) and progressive disease (PD).
Twenty patients with inflammatory breast cancer and one patient with locally advanced breast cancer received one cycle of bevacizumab followed by six cycles of bevacizumab plus docetaxel-doxorubicin before surgery. Baseline angiogenic/tumor markers were examined by immunohistochemistry and gene expression profiles were measured by Agilent Whole Human Genome arrays. All were assessed for clinical response.
Fourteen patients (67%, 95% confidence interval, 43-85.4%) had PR, five had SD, and two had PD. Expression of CD31 and platelet-derived growth factor receptor-beta (PDGFR-beta) in the tumor vasculature by immunohistochemistry was significantly associated with response (PR versus SD/PD; CD31 median, 33.5 versus 13.2; P = 0.0004; PDGFR-beta median, 5.9 versus 0.6; P = 0.01). Tumor VEGF-A showed a trend towards association with response (2.65 versus 0.25; P = 0.04). pVEGFR2(Y996), pVEGFR2(Y951), MVD, Ki67, apoptosis, grade, ER, HER-2/neu, and p53 were not associated with response. Twenty-six of 1,339 Gene Ontology (GO) classes at the gene transcriptional level were differentially expressed between patients with PR and SD/PD (P < 0.005). Representative significant GO classes include spindle (11 genes; P = 0.001), vascular endothelial growth factor receptor activity including PDGFR-beta (5 genes; P = 0.002), and cell motility including CD31 (80 genes; P = 0.005).
Baseline CD31, PDGFR-beta, and GO classes for vascular endothelial growth factor receptor activity and mitosis were significantly associated with response to bevacizumab followed by bevacizumab plus chemotherapy.

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    • "Although the search for a validated gene signature predictive for bevacizumab benefit did not bear fruit, some findings are consistently reported. Gene expression profiling studies in bevacizumab-treated patients with glioblastomas, breast and colon cancer identified predictive gene signatures with little or no gene overlap which possessed however a common repertoire of the gene functional ontologies implicated: cell proliferation, mitochondrial energy production, lipid metabolism, migration/invasion, hypoxia regulation and immune response [32-35]. The genes identified here are also characterized by the functional roles above. "
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