Validation and Clinical Utility of a 70-Gene Prognostic Signature for Women With Node-Negative Breast Cancer
Identifieur interne : 001601 ( Main/Exploration ); précédent : 001600; suivant : 001602Validation and Clinical Utility of a 70-Gene Prognostic Signature for Women With Node-Negative Breast Cancer
Auteurs : Marc Buyse ; Sherene Loi ; Laura Van'T Veer ; Giuseppe Viale ; Mauro Delorenzi ; Annuska M. Glas ; Mahasti Saghatchian D'Assignies ; Jonas Bergh ; Rosette Lidereau ; Paul Ellis ; Adrian Harris ; Jan Bogaerts ; Patrick Therasse ; Arno Floore ; Mohamed Amakrane ; Fanny Piette ; Emiel Rutgers ; Christos Sotiriou ; Fatima Cardoso ; Martine J. PiccartSource :
- Journal of the National Cancer Institute [ 0027-8874 ] ; 2006-09-06.
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 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.
Url:
DOI: 10.1093/jnci/djj329
Affiliations:
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<front><div type="abstract" xml:lang="en">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.</div>
</front>
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<affiliations><list></list>
<tree><noCountry><name sortKey="Amakrane, Mohamed" sort="Amakrane, Mohamed" uniqKey="Amakrane M" first="Mohamed" last="Amakrane">Mohamed Amakrane</name>
<name sortKey="Bergh, Jonas" sort="Bergh, Jonas" uniqKey="Bergh J" first="Jonas" last="Bergh">Jonas Bergh</name>
<name sortKey="Bogaerts, Jan" sort="Bogaerts, Jan" uniqKey="Bogaerts J" first="Jan" last="Bogaerts">Jan Bogaerts</name>
<name sortKey="Buyse, Marc" sort="Buyse, Marc" uniqKey="Buyse M" first="Marc" last="Buyse">Marc Buyse</name>
<name sortKey="Cardoso, Fatima" sort="Cardoso, Fatima" uniqKey="Cardoso F" first="Fatima" last="Cardoso">Fatima Cardoso</name>
<name sortKey="Delorenzi, Mauro" sort="Delorenzi, Mauro" uniqKey="Delorenzi M" first="Mauro" last="Delorenzi">Mauro Delorenzi</name>
<name sortKey="Ellis, Paul" sort="Ellis, Paul" uniqKey="Ellis P" first="Paul" last="Ellis">Paul Ellis</name>
<name sortKey="Floore, Arno" sort="Floore, Arno" uniqKey="Floore A" first="Arno" last="Floore">Arno Floore</name>
<name sortKey="Glas, Annuska M" sort="Glas, Annuska M" uniqKey="Glas A" first="Annuska M." last="Glas">Annuska M. Glas</name>
<name sortKey="Harris, Adrian" sort="Harris, Adrian" uniqKey="Harris A" first="Adrian" last="Harris">Adrian Harris</name>
<name sortKey="Lidereau, Rosette" sort="Lidereau, Rosette" uniqKey="Lidereau R" first="Rosette" last="Lidereau">Rosette Lidereau</name>
<name sortKey="Loi, Sherene" sort="Loi, Sherene" uniqKey="Loi S" first="Sherene" last="Loi">Sherene Loi</name>
<name sortKey="Piccart, Martine J" sort="Piccart, Martine J" uniqKey="Piccart M" first="Martine J." last="Piccart">Martine J. Piccart</name>
<name sortKey="Piette, Fanny" sort="Piette, Fanny" uniqKey="Piette F" first="Fanny" last="Piette">Fanny Piette</name>
<name sortKey="Rutgers, Emiel" sort="Rutgers, Emiel" uniqKey="Rutgers E" first="Emiel" last="Rutgers">Emiel Rutgers</name>
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<name sortKey="Therasse, Patrick" sort="Therasse, Patrick" uniqKey="Therasse P" first="Patrick" last="Therasse">Patrick Therasse</name>
<name sortKey="Van T Veer, Laura" sort="Van T Veer, Laura" uniqKey="Van T Veer L" first="Laura" last="Van'T Veer">Laura Van'T Veer</name>
<name sortKey="Viale, Giuseppe" sort="Viale, Giuseppe" uniqKey="Viale G" first="Giuseppe" last="Viale">Giuseppe Viale</name>
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