title: Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series.
abstract: OBJECTIVE
  Recently, a 76-gene prognostic signature able to predict distant metastases in lymph node-negative (N(-)) breast cancer patients was reported. The aims of this study conducted by TRANSBIG were to independently validate these results and to compare the outcome with clinical risk assessment.
  
  
  METHODS
  Gene expression profiling of frozen samples from 198 N(-) systemically untreated patients was done at the Bordet Institute, blinded to clinical data and independent of Veridex. Genomic risk was defined by Veridex, blinded to clinical data. Survival analyses, done by an independent statistician, were done with the genomic risk and adjusted for the clinical risk, defined by Adjuvant! Online.
  
  
  RESULTS
  The actual 5- and 10-year time to distant metastasis were 98% (88-100%) and 94% (83-98%), respectively, for the good profile group and 76% (68-82%) and 73% (65-79%), respectively, for the poor profile group. The actual 5- and 10-year overall survival were 98% (88-100%) and 87% (73-94%), respectively, for the good profile group and 84% (77-89%) and 72% (63-78%), respectively, for the poor profile group. We observed a strong time dependence of this signature, leading to an adjusted hazard ratio of 13.58 (1.85-99.63) and 8.20 (1.10-60.90) at 5 years and 5.11 (1.57-16.67) and 2.55 (1.07-6.10) at 10 years for time to distant metastasis and overall survival, respectively.
  
  
  CONCLUSIONS
  This independent validation confirmed the performance of the 76-gene signature and adds to the growing evidence that gene expression signatures are of clinical relevance, especially for identifying patients at high risk of early distant metastases.
authors.affiliation: Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Desmedt
authors.forename: Fanny
authors.initials: F
authors.lastname: Piette
authors.forename: Sherene
authors.initials: S
authors.lastname: Loi
authors.forename: Yixin
authors.initials: Y
authors.lastname: Wang
authors.forename: Françoise
authors.initials: F
authors.lastname: Lallemand
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haibe-Kains
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Mauro
authors.initials: M
authors.lastname: Delorenzi
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mahasti Saghatchian
authors.initials: MS
authors.lastname: d'Assignies
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: Rosette
authors.initials: R
authors.lastname: Lidereau
authors.forename: Paul
authors.initials: P
authors.lastname: Ellis
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Harris
authors.forename: Jan G M
authors.initials: JG
authors.lastname: Klijn
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
authors.forename: Fatima
authors.initials: F
authors.lastname: Cardoso
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Piccart
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D015203:Reproducibility of Results; D012306:Risk; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor