title: Systematic assessment of prognostic gene signatures for breast cancer shows distinct influence of time and ER status.
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.
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Montebello 0310 Oslo, Norway. xi.cameron@me.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhao
authors.forename: Einar Andreas
authors.initials: EA
authors.lastname: Rødland
authors.forename: Therese
authors.initials: T
authors.lastname: Sørlie
authors.forename: Hans Kristian Moen
authors.initials: HK
authors.lastname: Vollan
authors.forename: Hege G
authors.initials: HG
authors.lastname: Russnes
authors.forename: Vessela N
authors.initials: VN
authors.lastname: Kristensen
authors.forename: Ole Christian
authors.initials: OC
authors.lastname: Lingjærde
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D015331:Cohort Studies; D030541:Databases, Genetic; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D011379:Prognosis; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics*; D015203:Reproducibility of Results; D015996:Survival Rate / Q000639:trends; D013997:Time Factors
chemical_list: D011960:Receptors, Estrogen