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Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer

Y Nadler1, A M González2, R L Camp3

  • 1Department of Medicine, Yale University School of Medicine, New Haven, CT.

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|September 1, 2009
PubMed
Abstract

Insights

High Grb7 expression in breast cancer patients is linked to poorer survival. This finding suggests Grb7 could be a prognostic marker and a potential drug target, especially when coexpressed with HER2/neu.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Growth factor receptor-bound protein-7 (Grb7) is an adapter-type signaling protein.
  • Grb7 interacts with tyrosine kinases like HER2/neu.
  • Grb7-specific inhibitors are under development.

Purpose of the Study:

  • To assess Grb7 expression in breast cancer.
  • To determine the prognostic value of Grb7 expression.
  • To investigate the relationship between Grb7 and HER2/neu expression.

Main Methods:

  • Utilized tissue microarrays from 638 primary breast cancer specimens.
  • Employed Automated QUantitative Analysis for Grb7 expression measurement.
  • Assessed 15-year patient follow-up data.

Main Results:

  • High Grb7 expression correlated with decreased patient survival (P = 0.0034).
  • Grb7 remained an independent prognostic marker in multivariable analysis (P = 0.01).
  • High Grb7 was associated with high HER2/neu; coexpression worsened prognosis.

Conclusions:

  • High Grb7 expression identifies a subset of breast cancer patients with poor prognosis.
  • Grb7 may serve as a valuable prognostic marker and therapeutic target.
  • Coexpression with HER2/neu suggests cotargeting may benefit HER2/neu-positive breast cancers.

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