Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series

Christine Desmedt, Fanny Piette, Sherene Loi, Yixin Wang, Françoise Lallemand, Benjamin Haibe-Kains, Giuseppe Viale, Mauro Delorenzi, Yi Zhang, Mahasti Saghatchian D'Assignies, Jonas Bergh, Rosette Lidereau, Paul Ellis, Adrian L. Harris, Jan G M Klijn, John A. Foekens, Fatima Cardoso, Martine J. Piccart, Marc Buyse, Christos Sotiriou

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Abstract

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.

Original languageEnglish
Pages (from-to)3207-3214
Number of pages8
JournalClinical Cancer Research
Volume13
Issue number11
DOIs
Publication statusPublished - Jun 1 2007

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Breast Neoplasms
Neoplasm Metastasis
Genes
Survival
Gene Expression Profiling
Survival Analysis
Transcriptome
Research Design
Lymph Nodes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. / Desmedt, Christine; Piette, Fanny; Loi, Sherene; Wang, Yixin; Lallemand, Françoise; Haibe-Kains, Benjamin; Viale, Giuseppe; Delorenzi, Mauro; Zhang, Yi; D'Assignies, Mahasti Saghatchian; Bergh, Jonas; Lidereau, Rosette; Ellis, Paul; Harris, Adrian L.; Klijn, Jan G M; Foekens, John A.; Cardoso, Fatima; Piccart, Martine J.; Buyse, Marc; Sotiriou, Christos.

In: Clinical Cancer Research, Vol. 13, No. 11, 01.06.2007, p. 3207-3214.

Research output: Contribution to journalArticle

Desmedt, C, Piette, F, Loi, S, Wang, Y, Lallemand, F, Haibe-Kains, B, Viale, G, Delorenzi, M, Zhang, Y, D'Assignies, MS, Bergh, J, Lidereau, R, Ellis, P, Harris, AL, Klijn, JGM, Foekens, JA, Cardoso, F, Piccart, MJ, Buyse, M & Sotiriou, C 2007, 'Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series', Clinical Cancer Research, vol. 13, no. 11, pp. 3207-3214. https://doi.org/10.1158/1078-0432.CCR-06-2765
Desmedt, Christine ; Piette, Fanny ; Loi, Sherene ; Wang, Yixin ; Lallemand, Françoise ; Haibe-Kains, Benjamin ; Viale, Giuseppe ; Delorenzi, Mauro ; Zhang, Yi ; D'Assignies, Mahasti Saghatchian ; Bergh, Jonas ; Lidereau, Rosette ; Ellis, Paul ; Harris, Adrian L. ; Klijn, Jan G M ; Foekens, John A. ; Cardoso, Fatima ; Piccart, Martine J. ; Buyse, Marc ; Sotiriou, Christos. / Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 11. pp. 3207-3214.
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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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