Dynamics of IGF-1R expression during endocrine breast cancer treatment

Mol Imaging Biol. 2014 Aug;16(4):529-37. doi: 10.1007/s11307-014-0723-6.

Abstract

Purpose: The aim was to assess changes in insulin-like growth factor 1 receptor (IGF-1R) expression with immunoSPECT/CT and to study the dynamics of IGF-1R expression of human breast tumors during endocrine treatment.

Procedures: Mice with MCF-7 xenografts were treated with estradiol or tamoxifen, and IGF-1R expression was measured by immunohistochemistry and immunoSPECT/CT using (111)In-R1507 (anti-IGF-1R antibody). Moreover, IGF-1R expression was analyzed immunohistochemically on 22 human breast tumors, treated preoperatively with endocrine therapy.

Results: Estradiol resulted in an increased expression of IGF-1R, as measured by immunohistochemistry and immunoSPECT/CT. In contrast, tamoxifen resulted in a downregulation of IGF-1R, whereas this could not be measured with immunoSPECT/CT. A downregulation was also detectable in 9 out of 22 (41 %) human breast tumors after endocrine therapy.

Conclusions: Anti-estrogen treatment can cause a reduction in membranous IGF-1R expression. Based on these results, a combination of anti-IGF-1R antibodies with anti-estrogen therapy might not be a rational treatment strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Estradiol / pharmacology
  • Estradiol / therapeutic use*
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • Middle Aged
  • Receptor, IGF Type 1 / metabolism*
  • Receptor, IGF Type 1 / pharmacology
  • Tamoxifen / pharmacology
  • Tamoxifen / therapeutic use*
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Tamoxifen
  • Estradiol
  • Receptor, IGF Type 1
  • teprotumumab