Desmedt Christine, Piette Fanny, Loi Sherene, Wang Yixin, Lallemand Françoise, Haibe-Kains Benjamin, Viale Giuseppe, Delorenzi Mauro, Zhang Yi, d'Assignies Mahasti Saghatchian, Bergh Jonas, Lidereau Rosette, Ellis Paul, Harris Adrian L, Klijn Jan G M, Foekens John A, Cardoso Fatima, Piccart Martine J, Buyse Marc, Sotiriou Christos
Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Clin Cancer Res. 2007 Jun 1;13(11):3207-14. doi: 10.1158/1078-0432.CCR-06-2765.
Recently, a 76-gene prognostic signature able to predict distant metastases in lymph node-negative (N(-)) breast cancer patients was reported. The aims of this study conducted by TRANSBIG were to independently validate these results and to compare the outcome with clinical risk assessment.
Gene expression profiling of frozen samples from 198 N(-) systemically untreated patients was done at the Bordet Institute, blinded to clinical data and independent of Veridex. Genomic risk was defined by Veridex, blinded to clinical data. Survival analyses, done by an independent statistician, were done with the genomic risk and adjusted for the clinical risk, defined by Adjuvant! Online.
The actual 5- and 10-year time to distant metastasis were 98% (88-100%) and 94% (83-98%), respectively, for the good profile group and 76% (68-82%) and 73% (65-79%), respectively, for the poor profile group. The actual 5- and 10-year overall survival were 98% (88-100%) and 87% (73-94%), respectively, for the good profile group and 84% (77-89%) and 72% (63-78%), respectively, for the poor profile group. We observed a strong time dependence of this signature, leading to an adjusted hazard ratio of 13.58 (1.85-99.63) and 8.20 (1.10-60.90) at 5 years and 5.11 (1.57-16.67) and 2.55 (1.07-6.10) at 10 years for time to distant metastasis and overall survival, respectively.
This independent validation confirmed the performance of the 76-gene signature and adds to the growing evidence that gene expression signatures are of clinical relevance, especially for identifying patients at high risk of early distant metastases.
最近，有报道称一种76基因预后特征能够预测淋巴结阴性（N(-)）乳腺癌患者的远处转移情况。TRANSBIG开展的这项研究旨在独立验证这些结果，并将结果与临床风险评估进行比较。
在博尔德研究所对198例未经全身治疗的N(-)患者的冷冻样本进行基因表达谱分析，分析过程对临床数据保密且与Veridex无关。由Veridex在对临床数据保密的情况下定义基因组风险。由独立统计学家进行生存分析，分析时考虑基因组风险并根据由Adjuvant! Online定义的临床风险进行校正。
良好特征组实际发生远处转移的5年和10年时间分别为98%（88 - 100%）和94%（83 - 98%），不良特征组分别为76%（68 - 82%）和73%（65 - 79%）。良好特征组实际的5年和10年总生存率分别为98%（88 - 100%）和87%（73 - 94%），不良特征组分别为84%（77 - 89%）和72%（63 - 78%）。我们观察到该特征具有很强的时间依赖性，对于远处转移时间，5年时校正风险比为13.58（1.85 - 99.63），10年时为8.20（1.10 - 60.90）；对于总生存率，5年时校正风险比为5.11（1.57 - 16.67），10年时为2.55（1.07 - 6.10）。
这项独立验证证实了76基因特征的性能，并进一步证明基因表达特征具有临床相关性，特别是对于识别早期远处转移高风险患者。
