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.
journal_name
Cancer Genomics Proteomicsjournal_title
Cancer genomics & proteomicsauthors
Christodoulou C,Oikonomopoulos G,Koliou GA,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 HP,Pectasides D,Skarlos Pdoi
10.21873/cgp.20105subject
Has Abstractpub_date
2018-11-01 00:00:00pages
461-471issue
6eissn
1109-6535issn
1790-6245pii
15/6/461journal_volume
15pub_type
杂志文章abstract:BACKGROUND/AIM:The outcome of patients with advanced hepatocellular carcinoma (HCC) remains poor and therapeutic options, including sorafenib, the first anti-cancer drug proved to prolong survival in patients with advanced HCC, are limited. However, no clinically useful predictive biomarker for sorafenib has been repor...
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journal_title:Cancer genomics & proteomics
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journal_title:Cancer genomics & proteomics
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journal_title:Cancer genomics & proteomics
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更新日期:2006-03-01 00:00:00
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