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ARTICLE |
Validation and Clinical Utility of a 70-Gene Prognostic Signature for Women With Node-Negative Breast Cancer
On behalf of the TRANSBIG Consortium
Affiliations of authors: International Drug Development Institute, Brussels, Belgium (MB, MA, FP); Institut Jules Bordet, Brussels, Belgium (SL, CS, FC, MJP); Netherlands Cancer Institute, Amsterdam, The Netherlands (LvV, ER); European Institute of Oncology and University of Milan School of Medicine, Milan, Italy (GV); National Center of Competence in Research Molecular Oncology, Swiss Institute of Experimental Cancer Research, Epalinges & the Swiss Institute of Bioinformatics, Lausanne, Switzerland (MD); Agendia B.V. Amsterdam, The Netherlands (LvV, AMG, AF); Institut Gustave Roussy, Villejuif, France (MSd'A); Karolinska Institute, Stockholm, Sweden (JB); Centre René Huguenin and Institut National de la Santé et de la Recherche Médicale, St Cloud, France (RL); Guy's Hospital, London, U.K. (PE); John Radcliffe Hospital, Oxford, U.K. (AH); European Organisation for the Research and Treatment of Cancer Data Center, Brussels, Belgium (JB, PT)
Correspondence to: BIG/TRANSBIG Secretariat, Institut Jules Bordet, 121 Boulevard de Waterloo, 1000 Brussels, Belgium (e-mail: TRANSBIG{at}bordet.be).
Background: A 70-gene signature was previously shown to have prognostic value in patients with node-negative breast cancer. Our goal was to validate the signature in an independent group of patients. Methods: Patients (n = 307, with 137 events after a median follow-up of 13.6 years) from five European centers were divided into high- and low-risk groups based on the gene signature classification and on clinical risk classifications. Patients were assigned to the gene signature low-risk group if their 5-year distant metastasis–free survival probability as estimated by the gene signature was greater than 90%. Patients were assigned to the clinicopathologic low-risk group if their 10-year survival probability, as estimated by Adjuvant! software, was greater than 88% (for estrogen receptor [ER]–positive patients) or 92% (for ER-negative patients). Hazard ratios (HRs) were estimated to compare time to distant metastases, disease-free survival, and overall survival in high- versus low-risk groups. Results: The 70-gene signature outperformed the clinicopathologic risk assessment in predicting all endpoints. For time to distant metastases, the gene signature yielded HR = 2.32 (95% confidence interval [CI] = 1.35 to 4.00) without adjustment for clinical risk and hazard ratios ranging from 2.13 to 2.15 after adjustment for various estimates of clinical risk; clinicopathologic risk using Adjuvant! software yielded an unadjusted HR = 1.68 (95% CI = 0.92 to 3.07). For overall survival, the gene signature yielded an unadjusted HR = 2.79 (95% CI = 1.60 to 4.87) and adjusted hazard ratios ranging from 2.63 to 2.89; clinicopathologic risk yielded an unadjusted HR = 1.67 (95% CI = 0.93 to 2.98). For patients in the gene signature high-risk group, 10-year overall survival was 0.69 for patients in both the low– and high–clinical risk groups; for patients in the gene signature low-risk group, the 10-year survival rates were 0.88 and 0.89, respectively. Conclusions: The 70-gene signature adds independent prognostic information to clinicopathologic risk assessment for patients with early breast cancer.
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- Development and Evaluation of Therapeutically Relevant Predictive Classifiers Using Gene Expression Profiling
- Richard Simon
J Natl Cancer Inst 2006 98: 1169-1171.[Extract] [Full Text] [PDF]
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