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Insulin-like growth factor binding proteins 1 and 3 and breast cancer outcomes

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Abstract

The IGF family of growth factors is believed to play a role in the development and progression of breast cancer. We recently identified an adverse prognostic effect of insulin in breast cancer; we now report prognostic effects of circulating IGFBP's 1 and 3. 512 women with T1-3, N0-1, M0 breast cancer provided fasting blood which was analysed for IGFBP's 1 and 3. Information on body size, diet and traditional prognostic factors and treatment was obtained; women were followed for recurrence and death. IGFBP-1 levels correlated inversely with insulin levels (Spearman r = −0.60, p < 0.0001), reflecting known inhibition of IGFBP-1 gene expression by insulin. Insulin explained 36% of the variance in IGFBP-1 levels. IGFBP-1 levels were also correlated with obesity and diet. Levels of IGFBP-1 significantly predicted distant recurrence and death, hazard ratio (95% CI) for lower versus upper quartile 2.08 (1.20–3.61) and 3.0 (1.45–6.21), respectively. These effects persisted after adjustment for tumor-related variables and treatment but were not independent of insulin levels. High levels of IGFBP-3 predicted distant recurrence (hazard ratio upper v.s. lower quartile 1.8, 95% CI 1.1–3.0) but not death (hazard ratio 1.0, 95% CI 0.5–1.9). The effect on distant recurrence was restricted to postmenopausal women (hazard ratio 3.8, 95% CI 1.6–9.0) and to those with estrogen receptor positive tumors (p = 0.002). Prognostic effects of IGFBP-1 appear related to the known effect of insulin on IGFBP-1 gene expression. The adverse effect of IGFBP-3 on distant recurrence in postmenopausal women with estrogen receptor positive breast cancer should be further investigated.

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Authors and Affiliations

  1. Department of Medicine, Canada

    Pamela J. Goodwin, Marguerite Ennis, Kathleen I. Pritchard & Maureen E. Trudeau

  2. Division of Clinical Epidemiology, Samuel Lunenfeld Research Institute, Canada

    Pamela J. Goodwin & Nicky Hood

  3. Mount Sinai Hospital, Canada

    Pamela J. Goodwin, Warren Hartwick, Barry Hoffman & Nicky Hood

  4. University of Toronto, Canada

    Pamela J. Goodwin, Marguerite Ennis, Kathleen I. Pritchard, Maureen E. Trudeau, Jarley Koo, Warren Hartwick & Barry Hoffman

  5. Toronto-Sunnybrook Regional Cancer Centre, Canada

    Marguerite Ennis & Kathleen I. Pritchard

  6. Women's College Hospital, Canada

    Maureen E. Trudeau

  7. Department of Surgery, Canada

    Jarley Koo

  8. St. Michael's Hospital, Canada

    Jarley Koo

  9. Department of Pathology and Laboratory Medicine, Canada

    Warren Hartwick & Barry Hoffman

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  1. Pamela J. Goodwin
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  2. Marguerite Ennis
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  8. Nicky Hood
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Goodwin, P.J., Ennis, M., Pritchard, K.I. et al. Insulin-like growth factor binding proteins 1 and 3 and breast cancer outcomes. Breast Cancer Res Treat 74, 65–76 (2002). https://doi.org/10.1023/A:1016075709022

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  • DOI: https://doi.org/10.1023/A:1016075709022

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