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Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Systematic assessment of prognostic gene signatures for breast cancer shows distinct influence of time and ER status

Authors: Xi Zhao, Einar Andreas Rødland, Therese Sørlie, Hans Kristian Moen Vollan, Hege G Russnes, Vessela N Kristensen, Ole Christian Lingjærde, Anne-Lise Børresen-Dale

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

The aim was to assess and compare prognostic power of nine breast cancer gene signatures (Intrinsic, PAM50, 70-gene, 76-gene, Genomic-Grade-Index, 21-gene-Recurrence-Score, EndoPredict, Wound-Response and Hypoxia) in relation to ER status and follow-up time.

Methods

A gene expression dataset from 947 breast tumors was used to evaluate the signatures for prediction of Distant Metastasis Free Survival (DMFS). A total of 912 patients had available DMFS status. The recently published METABRIC cohort was used as an additional validation set.

Results

Survival predictions were fairly concordant across most signatures. Prognostic power declined with follow-up time. During the first 5 years of followup, all signatures except for Hypoxia were predictive for DMFS in ER-positive disease, and 76-gene, Hypoxia and Wound-Response were prognostic in ER-negative disease. After 5 years, the signatures had little prognostic power. Gene signatures provide significant prognostic information beyond tumor size, node status and histological grade.

Conclusions

Generally, these signatures performed better for ER-positive disease, indicating that risk within each ER stratum is driven by distinct underlying biology. Most of the signatures were strong risk predictors for DMFS during the first 5 years of follow-up. Combining gene signatures with histological grade or tumor size, could improve the prognostic power, perhaps also of long-term survival.
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Metadata
Title
Systematic assessment of prognostic gene signatures for breast cancer shows distinct influence of time and ER status
Authors
Xi Zhao
Einar Andreas Rødland
Therese Sørlie
Hans Kristian Moen Vollan
Hege G Russnes
Vessela N Kristensen
Ole Christian Lingjærde
Anne-Lise Børresen-Dale
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-211

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