Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York.
Exact Sciences Corporation, Redwood City, CA.
NEJM Evid. 2024 Aug;3(8):EVIDoa2300267. doi: 10.1056/EVIDoa2300267. Epub 2024 Jul 23.
The 21-gene recurrence score (RS) assay (Oncotype DX) is used to guide adjuvant chemotherapy use for patients with hormone receptor-positive, HER2 (human epidermal growth factor receptor 2)-negative, axillary node-negative breast cancer. Its role, however, in providing prognostic information for late distant recurrence when added to clinicopathologic prognostic factors is unknown.
A patient-specific meta-analysis including 10,004 women enrolled in three trials was updated using extended follow-up data from TAILORx, integrating the RS with histologic grade, tumor size, and age at surgery for the RSClin tool. Cox models integrating clinicopathologic factors and the RS were compared by using likelihood ratio (LR) tests. External validation of prognosis for distant recurrence in years 0 to 10 and 5 to 10 was performed in an independent cohort of 1098 women in a real-world registry.
RSClin provided significantly more prognostic information than either the clinicopathologic factors (ΔLR chi-square, 86.2; P<0.001) or RS alone (ΔLR chi-square, 131.0; P<0.001). The model was prognostic in an independent cohort for distant recurrence by 10 years after diagnosis (standardized hazard ratio, 1.56; 95% confidence interval, 1.25 to 1.94), was associated with late distant recurrence risk between 5 and 10 years after diagnosis (standardized hazard ratio, 1.78; 95% confidence interval, 1.25 to 2.55), and approximated the observed 10-year distant recurrence risk (Lin concordance, 0.87) and 5- to 10-year distant recurrence risk (Lin concordance, 0.92).
The 21-gene RS is prognostic for distant recurrence and overall survival in early breast cancer. A model integrating the 21-gene RS and clinicopathologic factors improved estimates of distant recurrence risk compared with either used individually and stratified late distant recurrence risk. (Funded by the National Cancer Institute, National Institutes of Health [U10CA180820, U10CA180794, UG1CA189859, U10CA180868, and U10CA180822] and others.).
21 基因复发评分（RS）检测（Oncotype DX）用于指导激素受体阳性、HER2（人表皮生长因子受体 2）阴性、腋窝淋巴结阴性乳腺癌患者的辅助化疗。然而，当加入临床病理预后因素时，其在提供晚期远处复发的预后信息方面的作用尚不清楚。
使用 TAILORx 的扩展随访数据，对包括三项试验在内的 10004 名患者进行了患者特异性的荟萃分析，将 RS 与组织学分级、肿瘤大小和手术时的年龄整合到 RSClin 工具中。通过似然比（LR）检验比较整合临床病理因素和 RS 的 Cox 模型。在真实世界注册中心的 1098 名女性独立队列中，对远处复发 0 至 10 年和 5 至 10 年的预后进行外部验证。
RSClin 提供了比临床病理因素（LR 卡方差异，86.2；P<0.001）或 RS 单独（LR 卡方差异，131.0；P<0.001）更显著的预后信息。该模型在独立队列中对诊断后 10 年的远处复发具有预后意义（标准化风险比，1.56；95%置信区间，1.25 至 1.94），与诊断后 5 至 10 年的远处复发风险相关（标准化风险比，1.78；95%置信区间，1.25 至 2.55），并接近观察到的 10 年远处复发风险（Lin 一致性，0.87）和 5 至 10 年远处复发风险（Lin 一致性，0.92）。
21 基因 RS 对早期乳腺癌的远处复发和总生存具有预后意义。与单独使用或分层使用的任何一种方法相比，整合 21 基因 RS 和临床病理因素的模型提高了远处复发风险的估计。（由美国国立卫生研究院国家癌症研究所资助[U10CA180820、U10CA180794、UG1CA189859、U10CA180868 和 U10CA180822]和其他机构）。
