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 FIR= 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 FIR= 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 FIR= 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.
Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer / M. Buyse, S. Loi, L. van't Veer, G. Viale, M. Delorenzi, A.M. Glas, M.S. d'Assignies, J. Bergh, R. Lidereau, P. Ellis, A. Harris, J. Bogaerts, P. Therasse, A. Floore, M. Amakrane, F. Piette, E. Rutgers, C. Sotiriou, F. Cardoso, M.J. Piccart. - In: JOURNAL OF THE NATIONAL CANCER INSTITUTE. - ISSN 0027-8874. - 98:17(2006 Sep 06), pp. 1183-1192.
Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer
G. Viale;
2006
Abstract
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 FIR= 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 FIR= 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 FIR= 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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