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Breast Cancer Research and Treatment

, Volume 106, Issue 1, pp 39–47 | Cite as

Insulin receptor is an independent predictor of a favorable outcome in early stage breast cancer

  • Anna Marie Mulligan
  • Frances P. O’Malley
  • Marguerite Ennis
  • I. George Fantus
  • Pamela J. GoodwinEmail author
Preclinical Study

Abstract

Fasting insulin is related to outcome in early breast cancer. We evaluated the expression of insulin receptor (IR) and its prognostic significance in patients with early stage breast cancer. Tumors from 191 patients with T1-3, N0-1, M0 breast cancer who were enrolled at a single center of a multicenter cohort study were used to construct microarrays with subsequent immunohistochemical evaluation of IR, IGF-IR, ER, PgR and HER2/neu. Correlation of biomarker expression with traditional prognostic factors, serum biochemistry (notably insulin) and clinical outcome was assessed. IR was strongly positive (Allred score = 8) in 54% of tumors. High IR expression significantly correlated with favorable prognostic markers (low tumor grade, lymph node negativity and progesterone receptor positivity) but not with fasting levels of circulating insulin. At a median follow-up of 9.1 years, high vs. low IR expression (an Allred score of 8 vs. 0-7) was associated with statistically significant improved distant disease-free survival (multivariate hazard ratio (HR) = 0.4; P = 0.027) and overall survival (multivariate HR = 0.26; P = 0.005). IR is highly expressed in the majority of early stage breast cancers but this expression is not clearly down-regulated in the presence of high insulin levels. Furthermore, high expression of IR is independently and significantly associated with more favorable clinical outcomes. Follow-up intervention research is recommended.

Keywords

Breast cancer Insulin  Insulin receptor Insulin-like growth factor receptor Prognostic markers 

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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Anna Marie Mulligan
    • 1
    • 2
  • Frances P. O’Malley
    • 1
    • 2
  • Marguerite Ennis
    • 3
  • I. George Fantus
    • 4
    • 5
    • 6
  • Pamela J. Goodwin
    • 2
    • 4
    • 7
    Email author
  1. 1.Pathology and Laboratory MedicineMount Sinai HospitalTorontoCanada
  2. 2.University of TorontoTorontoCanada
  3. 3.Applied StatisticianMarkhamCanada
  4. 4.Department of MedicineMount Sinai HospitalTorontoCanada
  5. 5.Department of PhysiologyUniversity of TorontoTorontoCanada
  6. 6.Banting and Best Diabetes CentreUniversity of TorontoTorontoCanada
  7. 7.Samuel Lunenfeld Research Institute at Mount Sinai HospitalTorontoCanada

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