title: Survivin is an independent prognostic marker for risk stratification of breast cancer patients.
abstract: BACKGROUND
  Results in previous qualitative studies of the association of the apoptosis inhibitor survivin with prognosis of breast cancer patients have been contradictory.
  
  
  METHODS
  Survivin mRNA was measured by quantitative TaqMan reverse transcription-PCR in 275 breast cancer tissues from patients with operable tumors and was correlated with established clinicopathologic factors, relapse-free survival [(RFS); 102 events], and overall survival [(OS); 81 events].
  
  
  RESULTS
  High survivin mRNA concentrations were found mainly in tissues from younger patients and in high-grade cancer tissues. High survivin concentrations were most strongly associated with estrogen receptor- or progesterone receptor-negative tumors. In univariate Cox regression analysis for RFS, survivin concentrations were significantly associated with poor prognosis with a hazard ratio (HR) of 1.99 (95% confidence interval, 1.31-3.02; P = 0.001) for every 10-fold increase in expression. For OS, a significant contribution of survivin to poor prognosis was found with a HR of 2.76 (1.67-4.55; P <0.001). Multivariate analyses were performed including established clinicopathologic factors. For RFS, age (P = 0.027), nodal category (P <0.001), and survivin [HR = 1.78 (1.18-2.68); P = 0.006] contributed significantly to the model. For OS, only nodal category (P <0.001) and survivin [HR = 3.05 (1.83-5.10); P <0.001] were significant.
  
  
  CONCLUSIONS
  Survivin demonstrates a strong, independent, association with poor prognosis. Survivin might be used as a new marker to stratify breast cancer patients for more optimal treatment modalities, or it could be a promising new target for therapy.
authors.affiliation: Departments of Chemical Endocrinology, Clinical Chemistry, Medical Oncology, University Medical Center Nijmegen, Nijmegen, The Netherlands. p.span@ace.umcn.nl
authors.forename: Paul N
authors.initials: PN
authors.lastname: Span
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Erwin T G
authors.initials: ET
authors.lastname: Wiegerinck
authors.forename: Vivianne C G
authors.initials: VC
authors.lastname: Tjan-Heijnen
authors.forename: Peggy
authors.initials: P
authors.lastname: Manders
authors.forename: Louk V A M
authors.initials: LV
authors.lastname: Beex
authors.forename: Jaques B
authors.initials: JB
authors.lastname: de Kok
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000175:diagnosis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000032:analysis* / Q000235:genetics; D015999:Multivariate Analysis; D009363:Neoplasm Proteins; D012333:RNA, Messenger / Q000032:analysis; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D015996:Survival Rate; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin