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Breast Cancer Research and Treatment

, Volume 74, Issue 1, pp 65–76 | Cite as

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

  • Pamela J. Goodwin
  • Marguerite Ennis
  • Kathleen I. Pritchard
  • Maureen E. Trudeau
  • Jarley Koo
  • Warren Hartwick
  • Barry Hoffman
  • Nicky Hood
Article

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.

breast cancer distant recurrence IGFBP1 IGFBP3 survival 

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Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Pamela J. Goodwin
    • 1
    • 2
    • 3
    • 4
  • Marguerite Ennis
    • 1
    • 5
    • 4
  • Kathleen I. Pritchard
    • 1
    • 5
    • 4
  • Maureen E. Trudeau
    • 1
    • 6
    • 4
  • Jarley Koo
    • 7
    • 8
    • 4
  • Warren Hartwick
    • 9
    • 3
    • 4
  • Barry Hoffman
    • 9
    • 3
    • 4
  • Nicky Hood
    • 2
    • 3
  1. 1.Department of MedicineCanada
  2. 2.Division of Clinical EpidemiologySamuel Lunenfeld Research InstituteCanada
  3. 3.Mount Sinai HospitalCanada
  4. 4.University of TorontoCanada
  5. 5.Toronto-Sunnybrook Regional Cancer CentreCanada
  6. 6.Women's College HospitalCanada
  7. 7.Department of SurgeryCanada
  8. 8.St. Michael's HospitalCanada
  9. 9.Department of Pathology and Laboratory MedicineCanada

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