Dataset Information

Individualized Survival and Treatment Response Predictions in Breast Cancer Patients: Involvements of Phospho-EGFR and Phospho-Her2/neu Proteins.

ABSTRACT: Our robust prediction system for individual breast cancer patients combines three well-known machine-learning classifiers to provide stable and accurate clinical outcome prediction (N=269). The average performance of the selected classifiers is used as the evaluation criterion in breast cancer outcome predictions. A profile (incorporating histology, lymph node status, tumor grade, tumor stage, ER, PR, Her2/neu, patient's age and smoking status) generated over 95% accuracy in individualized disease-free survival and treatment response predictions. Furthermore, our analysis demonstrated that the measurement of phospho-EGFR and phospho-Her2/neu is more powerful in breast cancer survival prediction than that of total EGFR and total Her2/neu (p < 0.05). The incorporation of hormone receptor status, Her2/neu, patient's age and smoking status into the traditional pathologic markers creates a powerful standard to perform individualized survival and treatment outcome predictions for breast cancer patients.

SUBMITTER: Guo L

PROVIDER: S-EPMC4282131 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Individualized Survival and Treatment Response Predictions in Breast Cancer Patients: Involvements of Phospho-EGFR and Phospho-Her2/neu Proteins.

Guo Lan L Abraham Jame J Flynn Daniel C DC Castranova Vincent V Shi Xianglin X Qian Yong Y

The open clinical cancer journal 20080501

Our robust prediction system for individual breast cancer patients combines three well-known machine-learning classifiers to provide stable and accurate clinical outcome prediction (<i>N</i>=269). The average performance of the selected classifiers is used as the evaluation criterion in breast cancer outcome predictions. A profile (incorporating histology, lymph node status, tumor grade, tumor stage, ER, PR, Her2/neu, patient's age and smoking status) generated over 95% accuracy in individualize ...[more]

PMID: 25558292

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Project description:HER2/neu (HER2) and cyclin E are important prognostic indicators in breast cancer. As both are involved in cell cycle regulation we analyzed whether there was a direct interaction between the two. HER2 and cyclin E expression levels were determined in 395 breast cancer patients. Patients with HER2-overexpression and high levels of cyclin E had decreased 5-year disease-specific survival compared with low levels of cyclin E (14% versus 89%, P<0.0001). In vitro studies were performed in which HER2-mediated activity in HER2-overexpressing breast cancer cell lines was downregulated by transfection with HER2 small interfering RNA or treatment with trastuzumab. Cyclin E expression levels were determined by western blot analysis, and functional effects analyzed using kinase assays, MTT assays were used to assess cell viability as a marker of proliferation and fluorescence-activated cell sorting analysis was used to determine cell cycle profiles. Decreased HER2-mediated signaling resulted in decreased expression of cyclin E, particularly the low molecular weight (LMW) isoforms. Decreased HER2 and LMW cyclin E expression had functional consequences, including decreased cyclin E-associated kinase activity and decreased proliferation, because of increased apoptosis and an increased accumulation of cells in the G1 phase. In vivo studies performed in a HER2-overexpressing breast cancer xenograft model confirmed the effects of trastuzumab on cyclin E expression. Given the relationship between HER2 and cyclin E, in vitro clonogenic assays were performed to assess combination therapy targeting both proteins. Isobologram analysis showed a synergistic interaction between the two agents (trastuzumab targeting HER2 and roscovitine targeting cyclin E). Taken together, these studies show that HER2-mediated signaling effects LMW cyclin E expression, which in turn deregulates the cell cycle. LMW cyclin E has prognostic and predictive roles in HER2-overexpressing breast cancer, warranting further study of its potential as a therapeutic target.

Dataset Information

Individualized Survival and Treatment Response Predictions in Breast Cancer Patients: Involvements of Phospho-EGFR and Phospho-Her2/neu Proteins.

Publications

Individualized Survival and Treatment Response Predictions in Breast Cancer Patients: Involvements of Phospho-EGFR and Phospho-Her2/neu Proteins.

Similar Datasets

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