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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Cohort Studies
  • Databases, Genetic*
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling / methods*
  • Humans
  • Prognosis
  • Receptors, Estrogen / biosynthesis
  • Receptors, Estrogen / genetics*
  • Reproducibility of Results
  • Survival Rate / trends
  • Time Factors

Substances

  • Receptors, Estrogen