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BMC Cancer. 2014 Mar 19;14:211. doi: 10.1186/1471-2407-14-211.

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

Author information

1
Department of Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Montebello 0310 Oslo, Norway. xi.cameron@me.com.

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.

PMID:
24645668
PMCID:
PMC4000128
DOI:
10.1186/1471-2407-14-211
[Indexed for MEDLINE]
Free PMC Article

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