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

ΤίτλοςEvaluation of the Insulin-like Growth Factor Receptor Pathway in Patients with Advanced Breast Cancer Treated with Trastuzumab.
Publication TypeJournal Article
Year of Publication2018
AuthorsChristodoulou, C., Oikonomopoulos G., Koliou G. Angeliki, Kostopoulos I., Kotoula V., Bobos M., Pentheroudakis G., Lazaridis G., Skondra M., Chrisafi S., Koutras A., Bafaloukos D., Razis E., Papadopoulou K., Papakostas P., Kalofonos H. P., Pectasides D., Skarlos P., Kalogeras K. T., & Fountzilas G.
JournalCancer Genomics Proteomics
Volume15
Issue6
Pagination461-471
Date Published2018 Nov-Dec
ISSN1790-6245
Λέξεις κλειδιάAdult, Aged, Aged, 80 and over, Breast Neoplasms, Disease-Free Survival, Female, Gene Expression Regulation, Humans, Middle Aged, Neoplasm Metastasis, Neoplasm Proteins, Receptor, IGF Type 1, Retrospective Studies, Signal Transduction, Survival Rate, Trastuzumab
Abstract

BACKGROUND: Trastuzumab is a monoclonal antibody against HER2-positive breast cancer. Despite improving the natural history of the disease, there is a number of patients who are resistant to it, whereas all patients will eventually develop resistance and disease will progress. Inconsistent preclinical data show that the IGF-R pathway may contribute to either de novo or acquired resistance to trastuzumab.
MATERIALS AND METHODS: In total, 227 trastuzumab-treated metastatic breast cancer patients were evaluated for IGF-1, IGF-1R, GLP-1R, Akt1, Akt2 Akt3 mRNA expression, and IGF-1Rα, IGF-1Rβ, IGF-2R protein expression.
RESULTS: Only 139 patients were truly HER2-positive by central assessment. Among HER2-positive patients, high Akt2 and GLP-1R mRNA expression showed a trend towards higher and lower risk of progression, respectively (HR=1.83, 95%CI=0.90-3.72, p=0.094 and HR=0.62, 95%CI=0.36-1.06, p=0.079), while high Akt1 and GLP-1R mRNA expression presented a trend towards unfavorable survival (HR=1.67, 95%CI=0.93-2.99, p=0.086 and HR=1.67, 95%CI=0.94-2.96, p=0.080). Among HER2-negative patients, high GLP-1R mRNA expression and negative stromal IGF-1Rβ protein expression showed a trend towards worse survival (HR=2.31, 95%CI=0.87-6.13, p=0.094 and HR=2.03, 95%CI=0.94-4.35, p=0.071, respectively). In the multivariate analyses, HER2-positive patients with high Akt1 and GLP-1R mRNA expression had a worse survival (HR=1.86, 95%CI=1.01-3.43, p=0.045 and HR=1.83, 95%CI=0.99-3.41, p=0.055, respectively).
CONCLUSION: This study revealed a crosstalk between the IGF-R pathway and HER2. There was evidence that high Akt1 and GLP-1R mRNA expression might affect survival among HER2-positive metastatic breast cancer patients treated with trastuzumab.

DOI10.21873/cgp.20105
Alternate JournalCancer Genomics Proteomics
PubMed ID30343280
PubMed Central IDPMC6299784

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