Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series.
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.
Desmedt
Christine
C
Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Piette
Fanny
F
Loi
Sherene
S
Wang
Yixin
Y
Lallemand
Françoise
F
Haibe-Kains
Benjamin
B
Viale
Giuseppe
G
Delorenzi
Mauro
M
Zhang
Yi
Y
d'Assignies
Mahasti Saghatchian
MS
Bergh
Jonas
J
Lidereau
Rosette
R
Ellis
Paul
P
Harris
Adrian L
AL
Klijn
Jan G M
JG
Foekens
John A
JA
Cardoso
Fatima
F
Piccart
Martine J
MJ
Buyse
Marc
M
Sotiriou
Christos
C
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
D014408:Biomarkers, Tumor