TY - JOUR
T1 - Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series
AU - Desmedt, Christine
AU - Piette, Fanny
AU - Loi, Sherene
AU - Wang, Yixin
AU - Lallemand, Françoise
AU - Haibe-Kains, Benjamin
AU - Viale, Giuseppe
AU - Delorenzi, Mauro
AU - Zhang, Yi
AU - D'Assignies, Mahasti Saghatchian
AU - Bergh, Jonas
AU - Lidereau, Rosette
AU - Ellis, Paul
AU - Harris, Adrian L.
AU - Klijn, Jan G M
AU - Foekens, John A.
AU - Cardoso, Fatima
AU - Piccart, Martine J.
AU - Buyse, Marc
AU - Sotiriou, Christos
PY - 2007/6/1
Y1 - 2007/6/1
N2 - Purpose: 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. Experimental Design: 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. Conclusion: 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.
AB - Purpose: 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. Experimental Design: 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. Conclusion: 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.
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U2 - 10.1158/1078-0432.CCR-06-2765
DO - 10.1158/1078-0432.CCR-06-2765
M3 - Article
C2 - 17545524
AN - SCOPUS:34250652449
VL - 13
SP - 3207
EP - 3214
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 11
ER -