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Breast Cancer Research and Treatment

, Volume 129, Issue 3, pp 725–736 | Cite as

Divergent effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple negative invasive ductal breast carcinoma

  • Hermien Hartog
  • Hugo M. Horlings
  • Bert van der Vegt
  • Bas Kreike
  • Abderrahim Ajouaou
  • Marc J. van de Vijver
  • H. Marike Boezen
  • Geertruida H. de Bock
  • Winette T. A. van der Graaf
  • Jelle WesselingEmail author
Preclinical study

Abstract

The insulin-like growth factor type 1 receptor (IGF1R) is involved in progression of breast cancer and resistance to systemic treatment. Targeting IGF1R signaling may, therefore, be beneficial in systemic treatment. We report the effect of IGF1R expression on prognosis in invasive ductal breast carcinoma (IDC), the most common type of breast cancer. Immunohistochemistry was performed on tumor tissue of a consecutive cohort of 429 female patients treated for operable primary IDC. Associations between IGF1R expression with clinicopathological parameters, disease free survival (DFS) and breast cancer specific survival (BCSS) were evaluated by multivariate analyses focusing on ER-positive and triple negative IDC (TN-IDC). To enlarge the TN-IDCs cohort, we analyzed a combined dataset of 51 TN-IDC tumors from our series with 64 TN-IDCs with similar clinicopathological parameters. Patients with tumors expressing cytoplasmic IGF1R have a longer DFS and BCSS (DFS: HR 0.46, 95% CI 0.27–0.49, P = 0.005, BCSS: HR 0.38, 95% CI 0.19–0.74, P = 0.005). This effect was most prominent in ER-positive tumors. However, in a combined series of 105 TN-IDCs cytoplasmic IGF1R expression was associated with a shorter DFS (HR = 2.29, 95% CI 1.08–4.84, P = 0.03), also when combined in a multivariate model, including well-known prognostic factors (HR 2.06; 95% CI 0.95–4.47; P = 0.07). IGF1R expression in ER-positive IDC is strongly related to a favorable DFS and BCSS, but to a shorter DFS in TN-IDC tumors. This divergent effect of IGF1R expression in subgroups of IDC may affect selection of patients for IGF1R targeted therapy.

Keywords

Insulin-like growth factor type 1 receptor Breast cancer Ductal type Prognosis Triple negative breast tumors Estrogen receptor 

Notes

Conflict of interest

No potential conflict of interest relevant to this article was reported.

Supplementary material

10549_2010_1256_MOESM1_ESM.doc (117 kb)
Supplementary material 1 (DOC 117 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Hermien Hartog
    • 1
  • Hugo M. Horlings
    • 4
  • Bert van der Vegt
    • 2
  • Bas Kreike
    • 4
    • 5
  • Abderrahim Ajouaou
    • 4
  • Marc J. van de Vijver
    • 7
  • H. Marike Boezen
    • 3
  • Geertruida H. de Bock
    • 3
  • Winette T. A. van der Graaf
    • 8
  • Jelle Wesseling
    • 6
    Email author
  1. 1.Department of Medical Oncology, University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
  2. 2.Department of Pathology, University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
  3. 3.Department of Epidemiology, University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
  4. 4.Division of Experimental TherapyNetherlands Cancer Institute/Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  5. 5.Department of RadiotherapyNetherlands Cancer Institute/Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  6. 6.Department of PathologyNetherlands Cancer Institute/Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  7. 7.Department of PathologyAcademic Medical CenterAmsterdam The Netherlands
  8. 8.Department of Medical OncologyRadboud University Nijmegen Medical CenterNijmegenThe Netherlands

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