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Ann Oncol. 2010 Mar;21(3):466-73. doi: 10.1093/annonc/mdp346. Epub 2009 Aug 28.

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

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

Abstract

BACKGROUND:

Growth factor receptor-bound protein-7 (Grb7) is an adapter-type signaling protein recruited to various tyrosine kinases, including HER2/neu. Grb7-specific inhibitors are in early development. As with other targeted therapies, response to therapy might be associated with target expression.

MATERIALS AND METHODS:

Tissue microarrays containing 638 primary breast cancer specimens with 15-year patient follow-up were employed to assess Grb7 expression using our Automated QUantitative Analysis method; cytokeratin defines pixels as breast cancer (tumor mask) within the histospot, and Grb7 expression within the mask is measured with Cy5-conjugated antibodies.

RESULTS:

High Grb7 expression was strongly associated with decreased survival in the entire cohort and in the node-positive subset (P = 0.0034 and P = 0.0019, respectively). On multivariable analysis, it remained an independent prognostic marker (P = 0.01). High Grb7 was strongly associated with high HER2/neu, and coexpression of these molecules was associated with worse prognosis than HER2/neu overexpression alone.

CONCLUSIONS:

High Grb7 defines a subset of breast cancer patients with decreased survival, indicating that Grb7 might be a valuable prognostic marker and drug target. Coexpression with HER2/neu indicates that cotargeting these molecules might be an effective approach for treating HER2/neu-positive breast cancers. Future studies using Grb7-targeting agents should include assessment of Grb7 levels.

PMID:
19717535
[PubMed - indexed for MEDLINE]
PMCID:
PMC2826097
Free PMC Article
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