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Experimental Therapeutics, Molecular Targets, and Chemical Biology

Increased β1 Integrin Is Associated with Decreased Survival in Invasive Breast Cancer

Evelyn S. Yao, Hui Zhang, Yunn-Yi Chen, Brian Lee, Karen Chew, Dan Moore and Catherine Park
Evelyn S. Yao
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Hui Zhang
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Yunn-Yi Chen
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Brian Lee
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Karen Chew
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Dan Moore
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Catherine Park
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DOI: 10.1158/0008-5472.CAN-06-2768 Published January 2007
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Abstract

Aberrant microenvironments and loss of balance in cell-extracellular matrix signaling are associated with breast cancer invasion, metastasis, and resistance to therapy. We have recently shown that increased β1 integrin signaling is involved in malignant progression and that inhibitory antibody to β1 integrin leads to selective apoptosis and decreased proliferation in three-dimensional cultures and in xenograft models of breast cancer in vivo. To investigate the clinical importance of these findings, in the present study we examined the expression of β1 integrin and extracellular β1 integrin ligands fibronectin and laminin-1 in a cohort of 249 breast cancer patients who had a median follow-up of 8.4 years. Among the 149 scorable cases, the highest β1 integrin intensity score (3+ versus 0–2+) was associated with significantly decreased 10-year overall survival of 48% versus 71% (P < 0.03) and decreased disease-free survival of 50% versus 80% (P < 0.05). Importantly, high fibronectin expression was associated with decreased overall and disease-free survival on univariate analysis (P < 0.04) and β1 integrin intensity score was significantly correlated with fibronectin expression (Kendall's tau-b = 0.19; P = 0.03). In a multivariate Cox proportional hazards model, β1 integrin intensity score remained a significant independent predictor of overall survival [hazard ratio (HR), 1.69; 95% confidence interval (95% CI), 1.19–2.38; P < 0.003] and disease-free survival (HR, 1.87; 95% CI, 1.21–2.88; P < 0.005). These findings show that β1 integrin expression has potential prognostic value in invasive breast cancer and that coexpression of fibronectin may help identify patients with more aggressive tumors who may benefit from targeted therapy. [Cancer Res 2007;67(2):659–64]

  • integrins
  • breast cancer
  • prognosis

Footnotes

    • Received July 27, 2006.
    • Revision received October 5, 2006.
    • Accepted November 14, 2006.
    • ©2007 American Association for Cancer Research.
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    Cancer Research: 67 (2)
    January 2007
    Volume 67, Issue 2
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    Increased β1 Integrin Is Associated with Decreased Survival in Invasive Breast Cancer
    Evelyn S. Yao, Hui Zhang, Yunn-Yi Chen, Brian Lee, Karen Chew, Dan Moore and Catherine Park
    Cancer Res January 15 2007 (67) (2) 659-664; DOI: 10.1158/0008-5472.CAN-06-2768

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    Increased β1 Integrin Is Associated with Decreased Survival in Invasive Breast Cancer
    Evelyn S. Yao, Hui Zhang, Yunn-Yi Chen, Brian Lee, Karen Chew, Dan Moore and Catherine Park
    Cancer Res January 15 2007 (67) (2) 659-664; DOI: 10.1158/0008-5472.CAN-06-2768
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