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Evaluation of the Insulin-like Growth Factor Receptor Pathway in Patients with Advanced Breast Cancer Treated with

Christos Christodoulou1, Georgios Oikonomopoulos2, Georgia Angeliki Koliou3

  • 1Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece c_christodoulou@yahoo.gr.

Cancer Genomics & Proteomics
|October 22, 2018
PubMed
Abstract

Insights

This study investigated the Insulin-like Growth Factor Receptor (IGF-R) pathway in HER2-positive breast cancer patients treated with trastuzumab. High Akt1 and GLP-1R mRNA expression correlated with worse survival, suggesting a link between these pathways and treatment resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacogenomics

Background:

  • Trastuzumab is a key therapy for HER2-positive breast cancer, but resistance limits its efficacy.
  • The Insulin-like Growth Factor Receptor (IGF-R) pathway's role in trastuzumab resistance is unclear.
  • Understanding resistance mechanisms is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the association between the IGF-R pathway and trastuzumab resistance in metastatic breast cancer.
  • To evaluate the expression of key pathway molecules in relation to treatment response and survival.
  • To explore potential biomarkers for predicting trastuzumab efficacy.

Main Methods:

  • Analysis of mRNA and protein expression of IGF-1, IGF-1R, GLP-1R, Akt1, Akt2, Akt3, IGF-1Rα, IGF-1Rβ, and IGF-2R in 227 trastuzumab-treated patients.
  • Correlation of molecular markers with progression-free survival and overall survival.
  • Multivariate analysis to identify independent prognostic factors.

Main Results:

  • High Akt1 and GLP-1R mRNA expression showed a trend towards unfavorable survival in HER2-positive patients.
  • Multivariate analysis confirmed that high Akt1 and GLP-1R mRNA expression were associated with worse survival in HER2-positive patients (HR=1.86, p=0.045 and HR=1.83, p=0.055, respectively).
  • Trends towards altered survival were also observed in HER2-negative patients based on GLP-1R and IGF-1Rβ expression.

Conclusions:

  • Evidence suggests a crosstalk between the IGF-R pathway and HER2 signaling in breast cancer.
  • High Akt1 and GLP-1R mRNA expression may serve as indicators of poor survival in HER2-positive metastatic breast cancer patients receiving trastuzumab.
  • Further research is warranted to elucidate these interactions and develop targeted therapeutic strategies.
Keywords:
HER2-negative breast cancerHER2-positive breast cancerIGF-Radvanced breast cancertrastuzumab

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