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A population-based gene signature is predictive of breast cancer survival and chemoresponse.

Authors
Rathnagiriswaran-S; Wan-YW; Abraham-J; Castranova-V; Qian-Y; Guo-NL
Source
Int J Oncol 2010 Mar; 36(3):607-616
NIOSHTIC No.
20036454
Abstract
It remains a critical issue to improve the survival rate in patients with recurrent or metastatic breast cancer. This study sought to develop a prognostic scheme based on a 28-gene signature in a broad patient population, including those with advanced disease. Clinically annotated transcriptional profiles of 1,734 breast cancer patients were obtained to validate the 28-gene signature in prognostic categorization. The 28-gene signature generated significant patient stratification with regard to breast cancer disease-free survival (log-rank P<0.0001; n=1,337) and overall survival (log-rank P<0.0001; n=806) in Kaplan-Meier analyses. The gene expression signature provides refined prognosis of disease-free survival (log-rank P<0.006; Kaplan-Meier analysis) within each classic clinicopathologic factor-defined subgroup, including LN-, LN+, ER-, ER+ and tumor grade II. Furthermore, it was investigated whether this gene signature predicts chemoresponse to drugs commonly used to treat breast cancer. The mRNA expression levels of this gene signature in NCI-60 cell lines were used to predict chemoresponse to CMF, tamoxifen, paclitaxel, docetaxel, and doxorubicin (adriamycin). The 28-gene prognostic signature accurately (P<0.02) predicted chemotherapeutic response to the studied drugs. This study confirmed the prognostic applicability of the breast cancer gene signature in a broad clinical setting. This prognostic signature is also predictive of drug response in cancer cell lines.
Keywords
Cancer; Breast-cancer; Epidemiology; Statistical-analysis; Genes; Gene-mutation; Genetics; Author Keywords: gene signature; breast cancer prognosis; chemosensitivity prediction; NCI-60 cell lines
Contact
Dr Nancy L. Guo, Mary Babb Randolph Cancer Center, Morgantown, WV 26506-9300, USA
CODEN
IJONES
Publication Date
20100301
Document Type
Journal Article
Email Address
lguo@hsc.wvu.edu
Fiscal Year
2010
NTIS Accession No.
NTIS Price
Issue of Publication
3
ISSN
1019-6439
NIOSH Division
HELD
Source Name
International Journal of Oncology
State
WV
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