70基因预后特征对淋巴结阴性乳腺癌女性患者的验证及临床应用价值

Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer.

作者信息

Buyse Marc, Loi Sherene, van't Veer Laura, Viale Giuseppe, Delorenzi Mauro, Glas Annuska M, d'Assignies Mahasti Saghatchian, Bergh Jonas, Lidereau Rosette, Ellis Paul, Harris Adrian, Bogaerts Jan, Therasse Patrick, Floore Arno, Amakrane Mohamed, Piette Fanny, Rutgers Emiel, Sotiriou Christos, Cardoso Fatima, Piccart Martine J

机构信息

International Drug Development Institute, Brussels, Belgium.

出版信息

J Natl Cancer Inst. 2006 Sep 6;98(17):1183-92. doi: 10.1093/jnci/djj329.

DOI:10.1093/jnci/djj329

PMID:16954471

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.

摘要

背景

先前研究表明，一种70基因特征对淋巴结阴性乳腺癌患者具有预后价值。我们的目标是在一组独立患者中验证该特征。

方法

来自欧洲五个中心的患者（n = 307，中位随访13.6年后有137例事件发生）根据基因特征分类和临床风险分类分为高风险组和低风险组。如果基因特征估计的5年无远处转移生存率大于90%，则将患者分配到基因特征低风险组。如果根据辅助软件估计的10年生存率，雌激素受体（ER）阳性患者大于88%，ER阴性患者大于92%，则将患者分配到临床病理低风险组。估计风险比（HR）以比较高风险组和低风险组发生远处转移的时间、无病生存期和总生存期。

结果

在预测所有终点方面，70基因特征优于临床病理风险评估。对于远处转移时间，基因特征在未调整临床风险时产生的HR = 2.32（95%置信区间[CI] = 1.35至4.00），在调整各种临床风险估计值后，风险比范围为2.13至2.15；使用辅助软件的临床病理风险产生的未调整HR = 1.68（95% CI = 0.92至3.07）。对于总生存期，基因特征产生的未调整HR = 2.79（95% CI = 1.60至4.87），调整后的风险比范围为2.63至2.89；临床病理风险产生的未调整HR = 1.67（95% CI = 0.93至2.98）。对于基因特征高风险组的患者，临床风险低和高的两组患者10年总生存期均为0.69；对于基因特征低风险组的患者，10年生存率分别为0.88和0.89。