SOLTI Breast Cancer Research Group, Barcelona; Statistics Unit, Vall d'Hebron Institute of Oncology, Barcelona.
SOLTI Breast Cancer Research Group, Barcelona; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona; Medical Oncology Department, Hospital Clínic, Barcelona.
ESMO Open. 2024 Mar;9(3):102388. doi: 10.1016/j.esmoop.2024.102388. Epub 2024 Mar 4.
The HER2DX risk-score has undergone rigorous validation in prior investigations involving patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive (HER2+) breast cancer. In this study, we present the outcomes of the HER2DX risk-score within the most recent release of the Sweden Cancerome Analysis Network-Breast (SCAN-B) HER2+ cohort. This updated examination benefits from a larger patient sample, an extended follow-up duration, and detailed treatment information.
Clinical and RNAseq data from the SCAN-B dataset were retrieved from Gene Expression Omnibus (GSE81538). Among the 6600 patients, 819 had HER2+ breast cancer, with 757 individuals with research-based HER2DX risk-scores and corresponding survival outcomes. The HER2DX risk-score was evaluated (i) as a continuous variable and (ii) using predefined cut-offs. The primary endpoint for this study was overall survival (OS). The Kaplan-Meier method and Cox models were used to estimate OS and a multistate model with four states was fitted to better characterize patients' follow-up.
The median follow-up time was 7.5 years (n = 757). The most common systemic therapy was chemotherapy with trastuzumab (82.0%) and most tumors were classified as T1-T2 (97.1%). The HER2DX risk-score as a continuous variable was significantly associated with OS after adjustment for clinical variables and treatment regimen [hazard ratios (HR) per 10-unit increment = 1.31, 95% confidence interval (CI) 1.13-1.51, P < 0.001] as well as within predefined risk groups (high versus low; HR = 2.57, 95% CI 1.36-4.85, P < 0.001). Patients classified as HER2DX high-risk also had higher risk of (i) breast cancer recurrence and (ii) death without previous recurrence. Within the subgroup of HER2+ T1N0 tumors (n = 297), those classified as high-risk demonstrated inferior OS compared to low-risk tumors (7-year OS 77.8% versus 96.8%, P < 0.001). The HER2DX mRNA ERBB2 score was associated with clinical HER2 status (area under the receiver operating characteristic curve = 0.91).
In patients with early-stage HER2+ breast cancer, HER2DX risk-score provides prognostic information beyond clinicopathological variables, including treatment regimen with or without trastuzumab.
HER2DX 风险评分在先前涉及人表皮生长因子受体 2（HER2）阳性（HER2+）早期乳腺癌患者的研究中已经经过严格验证。在本研究中，我们展示了最新版瑞典癌症组分析网络-乳腺（SCAN-B）HER2+队列中 HER2DX 风险评分的结果。此次更新的检查得益于更大的患者样本、更长的随访时间和详细的治疗信息。
从基因表达 Omnibus（GSE81538）中检索了来自 SCAN-B 数据集的临床和 RNAseq 数据。在 6600 名患者中，有 819 名患有 HER2+乳腺癌，其中 757 名患者具有基于研究的 HER2DX 风险评分和相应的生存结果。评估了 HER2DX 风险评分（i）作为连续变量和（ii）使用预定义的截止值。本研究的主要终点是总生存期（OS）。使用 Kaplan-Meier 方法和 Cox 模型估计 OS，并拟合了一个具有四个状态的多状态模型，以更好地描述患者的随访情况。
中位随访时间为 7.5 年（n=757）。最常见的系统治疗是曲妥珠单抗联合化疗（82.0%），大多数肿瘤被归类为 T1-T2（97.1%）。HER2DX 风险评分作为连续变量，在调整临床变量和治疗方案后，与 OS 显著相关[每增加 10 个单位的风险比（HR）=1.31，95%置信区间（CI）1.13-1.51，P<0.001]，以及在预定风险组内（高 vs 低；HR=2.57，95%CI 1.36-4.85，P<0.001）。被归类为 HER2DX 高风险的患者也有更高的（i）乳腺癌复发和（ii）无复发前死亡的风险。在 HER2+T1N0 肿瘤亚组（n=297）中，与低风险肿瘤相比，高风险肿瘤的 OS 较差（7 年 OS 77.8%对 96.8%，P<0.001）。HER2DX mRNA ERBB2 评分与临床 HER2 状态相关（接受者操作特征曲线下面积=0.91）。
在早期 HER2+乳腺癌患者中，HER2DX 风险评分提供了比临床病理变量更具预后意义的信息，包括有无曲妥珠单抗的治疗方案。
