Validation and Clinical Utility of a 70-Gene Prognostic Signature for Women With Node-Negative Breast Cancer

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ID: 295801
2006
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Abstract
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.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.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.The 70-gene signature adds independent prognostic information to clinicopathologic risk assessment for patients with early breast cancer.
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Authors Marc Buyse, Sherene Loi, Laura van't Veer, Giuseppe Viale, Mauro Delorenzi, Annuska M. Glas, Mahasti Saghatchian d'Assignies, Jonas Bergh, Rosette Lidereau, Peter Ellis, Adrian L. Harris, Jan Bogaerts, Patrick Therasse, Arno Floore, Mohamed Amakrane, Fanny Piette, Emiel J. Rutgers, Christos Sotiriou, Fátima Cardoso, Martine Piccart
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Journal JNCI Journal of the National Cancer Institute
Year 2006
DOI
10.1093/jnci/djj329
URL
https://academic.oup.com/jnci/article-pdf/98/17/1183/7687596/djj329.pdf
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