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E-GEOD-7390 - Transcription profiling of human primary breast tumors to validate a 76-gene prognostic signature reveals strong time dependence of the 76-gene prognostic signature

Submitted on 28 March 2007, released on 16 June 2008, last updated on 27 March 2012
Homo sapiens
Samples (198)
Array (1)
Protocols (4)
Background: 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. Materials and Methods: Gene expression profiling of frozen samples from 198 N- systemically untreated patients was performed 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 performed 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 (TDM) were 98% (88%-100%) and 94% (83%-98%) respectively for the good profile group and 76% (68%- 82%) and 73% (65%-79%) for the poor profile group. The actual 5- and 10-year overall survival (OS) were 98% (88%-100%) and 87% (73%-94%) respectively for the good profile group and 84% (77%-89%) and 72% (63%-78%) for the poor profile group. We observed a strong time-dependency of this signature, leading to an adjusted HR 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 TDM and OS 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. Experiment Overall Design: dataset of microarray experiments from primary breast tumors used to validate the 76-gene signature (VERIDEX). No replicate, no reference sample.
Experiment types
transcription profiling by array, unknown experiment type
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. Clin Cancer Res 13(11):3207-14 (2007)