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 ( = 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, < 0.001] as well as within predefined risk groups (high versus low; HR = 2.57, 95% CI 1.36-4.85, < 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 ( = 297), those classified as high-risk demonstrated inferior OS compared to low-risk tumors (7-year OS 77.8% versus 96.8%, < 0.001). The HER2DX mRNA 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.

中文翻译：

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HER2DX 在早期 HER2 阳性乳腺癌中的预后价值：对瑞典癌症组分析网络 - 乳腺数据集 (SCAN-B) 中 757 名患者的综合分析

HER2DX 风险评分在之前针对早期人类表皮生长因子受体 2 (HER2) 阳性 (HER2+) 乳腺癌患者的调查中经过了严格验证。在本研究中，我们展示了瑞典癌症组分析网络 - 乳腺癌 (SCAN-B) HER2+ 队列最新发布的 HER2DX 风险评分结果。此次更新的检查受益于更大的患者样本、更长的随访时间和详细的治疗信息。 SCAN-B 数据集中的临床和 RNAseq 数据取自 Gene Expression Omnibus (GSE81538)。在 6600 名患者中，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。 HER2DX 风险评分通过 (i) 作为连续变量和 (ii) 使用预定义的截止值进行评估。这项研究的主要终点是总生存期（OS）。 Kaplan-Meier 方法和 Cox 模型用于估计 OS，并拟合了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 (= 757)。最常见的全身治疗是曲妥珠单抗化疗（82.0%），大多数肿瘤被分类为T1-T2（97.1%）。调整临床变量和治疗方案后，HER2DX 风险评分作为连续变量与 OS 显着相关[每 10 单位增量的风险比 (HR) = 1.31，95% 置信区间 (CI) 1.13-1.51，< 0.001]以及预定义风险组内（高风险组与低风险组；HR = 2.57，95% CI 1.36-4.85，< 0.001）。被归类为 HER2DX 高风险的患者 (i) 乳腺癌复发和 (ii) 先前未复发的死亡风险也较高。在 HER2+ T1N0 肿瘤亚组 (= 297) 中，与低风险肿瘤相比，被归类为高风险的肿瘤表现出较差的 OS（7 年 OS 77.8% vs 96.8%，< 0.001）。 HER2DX mRNA 评分与临床 HER2 状态相关（受试者工作特征曲线下面积 = 0.91）。对于早期 HER2+ 乳腺癌患者，HER2DX 风险评分提供临床病理学变量之外的预后信息，包括使用或不使用曲妥珠单抗的治疗方案。