GRB7 protein over-expression and clinical outcome in breast cancer

Betsy Ramsey, Tao Bai, Amy Hanlon Newell, Megan Troxell, Byung Park, Susan Olson, Edward Keenan, Shiuh Wen Luoh

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The growth factor receptor-bound protein-7 gene (GRB7) encodes a multi-domain signal transduction molecule. The purpose of this study was to examine the clinical significance of GRB7 protein expression in human breast cancer. Western blotting analysis of protein extracts from 563 annotated frozen breast tumors was performed. Expression status of GRB7 and HER-2 was correlated with clinical covariates and outcomes. Cox proportional hazards were used to identify factors associated with breast cancer-free interval. The median follow-up was 71 months. P values <0.05 were considered statistically significant (two-sided). A discrepancy between HER-2 and GRB7 protein over-expression was observed. GRB7 protein over-expression was associated with negative estrogen and progesterone receptor status, higher tumor grade, larger primary tumor size, (more) axillary lymph node involvement, higher clinical stage, and shortened breast cancer-free interval. HER-2 protein over-expression was associated only with higher tumor grade. Multi-variate analysis revealed that GRB7 protein over-expression was an independent adverse prognostic factor for breast cancer-free interval (hazard ratio 1.69, 95% confidence interval 1.07-2.67; P = 0.024). The same was true of the subset of patients who did not receive any adjuvant systemic therapy (hazard ratio 1.68, 95% confidence interval 1.16-2.31; P = 0.0055). Using FISH analysis, 32/32 (100%; 95% CI 89-100%) tumors which over-expressed both HER-2 and GRB7 proteins and 1/35 (3%; 95% CI 0-15%) tumors with HER-2 but no GRB7 protein over-expression with Western blotting analysis demonstrated HER-2 gene amplification. GRB7 protein over-expression is an independent adverse prognostic factor in human breast cancer.

Original languageEnglish (US)
Pages (from-to)659-669
Number of pages11
JournalBreast Cancer Research and Treatment
Volume127
Issue number3
DOIs
StatePublished - Jun 1 2011

Keywords

  • Biomarker
  • Breast cancer
  • GRB7 gene
  • Gene amplification
  • HER-2 gene
  • Oncogenes
  • Prognostic marker
  • Signal transduction

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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