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Imaging, Diagnosis, Prognosis

Glycoprotein Nonmetastatic B Is an Independent Prognostic Indicator of Recurrence and a Novel Therapeutic Target in Breast Cancer

April A.N. Rose, Andrée-Anne Grosset, Zhifeng Dong, Caterina Russo, Patricia A. MacDonald, Nicholas R. Bertos, Yves St-Pierre, Ronit Simantov, Michael Hallett, Morag Park, Louis Gaboury and Peter M. Siegel
April A.N. Rose
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Andrée-Anne Grosset
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Zhifeng Dong
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Caterina Russo
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Patricia A. MacDonald
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Nicholas R. Bertos
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Yves St-Pierre
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Ronit Simantov
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Michael Hallett
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Morag Park
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Louis Gaboury
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Peter M. Siegel
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DOI: 10.1158/1078-0432.CCR-09-1611
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Abstract

Purpose: Although the murine orthologue of glycoprotein nonmetastatic B (GPNMB), Osteoactivin, promotes breast cancer metastasis in an in vivo mouse model, its importance in human breast cancer is unknown. We have examined the significance of GPNMB expression as a prognostic indicator of recurrence and assessed its potential as a novel therapeutic target in breast cancer.

Experimental Design: The clinical significance of GPNMB expression in breast cancer was addressed by analyzing GPNMB levels in several published gene expression data sets and two independent tissue microarrays derived from human breast tumors. GPNMB-expressing human breast cancer cell lines were further used to validate a toxin-conjugated anti-GPNMB antibody as a novel therapeutic agent.

Results: GPNMB expression correlates with shorter recurrence times and reduced overall survival of breast cancer patients. Epithelial-specific GPNMB staining is an independent prognostic indicator for breast cancer recurrence. GPNMB is highly expressed in basal and triple-negative breast cancers and is associated with increased risk of recurrence within this subtype. GPNMB expression confers a more migratory and invasive phenotype on breast cancer cells and sensitizes them to killing by CDX-011 (glembatumumab vedotin), a GPNMB-targeted antibody-drug conjugate.

Conclusions: GPNMB expression is associated with the basal/triple-negative subtype and is a prognostic marker of poor outcome in patients with breast cancer. CDX-011 (glembatumumab vedotin) is a promising new targeted therapy for patients with metastatic triple-negative breast cancers, a patient population that currently lacks targeted-therapy options. Clin Cancer Res; 16(7); OF1–10

Keywords
  • Breast Cancer
  • Triple Negative
  • GPNMB
  • Recurrence

Footnotes

  • Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).

    • Received June 24, 2009.
    • Revision received January 23, 2010.
    • Accepted January 25, 2010.
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Published OnlineFirst March 9, 2010
doi: 10.1158/1078-0432.CCR-09-1611

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Glycoprotein Nonmetastatic B Is an Independent Prognostic Indicator of Recurrence and a Novel Therapeutic Target in Breast Cancer
April A.N. Rose, Andrée-Anne Grosset, Zhifeng Dong, Caterina Russo, Patricia A. MacDonald, Nicholas R. Bertos, Yves St-Pierre, Ronit Simantov, Michael Hallett, Morag Park, Louis Gaboury and Peter M. Siegel
Clin Cancer Res March 9 2010 DOI: 10.1158/1078-0432.CCR-09-1611

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Glycoprotein Nonmetastatic B Is an Independent Prognostic Indicator of Recurrence and a Novel Therapeutic Target in Breast Cancer
April A.N. Rose, Andrée-Anne Grosset, Zhifeng Dong, Caterina Russo, Patricia A. MacDonald, Nicholas R. Bertos, Yves St-Pierre, Ronit Simantov, Michael Hallett, Morag Park, Louis Gaboury and Peter M. Siegel
Clin Cancer Res March 9 2010 DOI: 10.1158/1078-0432.CCR-09-1611
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Clinical Cancer Research
eISSN: 1557-3265
ISSN: 1078-0432

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