HER2DX and survival outcomes in early-stage HER2-positive breast cancer: an individual patient-level meta-analysis.

Although HER2-targeted therapies have markedly improved outcomes, current clinical-pathological variables and pathological complete response after neoadjuvant therapy are insufficient to fully capture biological heterogeneity and guide personalised treatment.

尽管HER2靶向治疗显著改善了治疗结果，但目前的临床病理变量和新辅助治疗后的病理完全缓解仍不足以完全捕捉生物学异质性并指导个性化治疗。

HER2DX is a genomic test that integrates tumour biology and clinical data to stratify risk.

HER2DX 是一种整合肿瘤生物学和临床数据的基因组测试，用于分层风险。

Here, we conducted an individual patient-level meta-analysisto evaluate the association between the HER2DX risk score and survival outcomes in early-stage HER2-positive breast cancer.

在这里，我们进行了一项个体患者水平的荟萃分析，以评估 HER2DX 风险评分与早期 HER2 阳性乳腺癌生存结果之间的关联。

Methods

We conducted a systematic reviewand individual patient-level meta-analysisusing data from studies of stage 1-3 HER2-positive breast cancer, incorporating HER2DX risk scores, clinical information, and survival outcomes.

我们开展了一项系统综述和个体患者水平的荟萃分析，利用了1-3期HER2阳性乳腺癌研究的数据，整合了HER2DX风险评分、临床信息及生存结果。

A systematic literature search was conducted in PubMed on Dec 15, 2024, and complemented by a review of in-house databases to identify eligible studies with HER2DX testing and patient-level data.

我们在2024年12月15日在PubMed进行了系统文献检索，并补充审查了内部数据库，以识别具有HER2DX检测和患者级数据的合格研究。

Eligible studies were required to include more than 50 patients with HER2-positive early breast cancer treated with anti-HER2 therapy, with available survival outcomes, and HER2DX testing performed.

符合条件的研究必须包括超过50名接受抗HER2治疗的HER2阳性早期乳腺癌患者，具有可获得的生存结果，并进行了HER2DX检测。

Individual-level data were requested from study investigators or accessed through public repositories.

向研究调查员请求了个别数据，或通过公共数据库访问。

HER2DX risk score was evaluated as continuous score and as a risk group using pre-established cutoffs (low vs high).

HER2DX风险评分被评估为连续分数以及使用预先设定的截断值（低风险与高风险）作为风险组。

The primary endpoint of the study was event-free survival, estimated using the Kaplan-Meier method.

该研究的主要终点是无事件生存率，使用Kaplan-Meier方法进行估计。

Univariable and multivariable stratified Cox models were used to estimate stratified hazard ratios (HRs).

使用单变量和多变量分层Cox模型来估计分层风险比（HRs）。

The study was registered in PROSPERO (CRD42025634137).

该研究已在PROSPERO注册（CRD42025634137）。

Results

11 studies met the inclusion criteria (APT, ATEMPT, CALGB40601, DAPHNe, GOM-HGUGM-2018-05, NEOHER, SOLTI-PAMELA, PHERGain, HUAC, SCAN-B, and DFCI-14-409) and were selected for the meta-analysis.

符合纳入标准的11项研究（APT、ATEMPT、CALGB40601、DAPHNe、GOM-HGUGM-2018-05、NEOHER、SOLTI-PAMELA、PHERGain、HUAC、SCAN-B和DFCI-14-409）被选用于荟萃分析。

Of 3244 patients identified across the selected studies, 2518 were included in the analysis (those with available HER2DX clinical data and survival outcomes).

在选定的研究中，共有3244名患者被识别出来，其中2518名患者的HER2DX临床数据和生存结果可用，因此被纳入分析。

The median follow-up was 6·1 years (95% CI 6·0-6·3).

中位随访时间为6.1年（95%置信区间6.0-6.3年）。

Of 2518 patients, 891 (35·4%) had stage 1 disease, 1133 (45·0%) stage 2 disease, and 494 (19·6%) stage 3 disease.

在2518名患者中，891名（35.4%）患有1期疾病，1133名（45.0%）患有2期疾病，494名（19.6%）患有3期疾病。

Hormone receptor-positive disease was present in 1660 (65·9%) of 2518 patients and 1259 (50·0%) of 2518 patients had a high HER2DX risk score.

在2518名患者中，1660名（65.9%）存在激素受体阳性疾病，2518名患者中有1259名（50.0%）具有高HER2DX风险评分。

In the multivariable analysis, HER2DX as a continuous variable was independently associated with event-free survival (stratified HR per 10-unit increment 1·25, 95% CI 1·14-1·38; p<0·0001).

在多变量分析中，HER2DX作为连续变量与无事件生存期独立相关（分层风险比每增加10单位为1.25，95%置信区间1.14-1.38；p<0.0001）。

Patients classified as HER2DX low risk had a 6-year event-free survival rate of 93·6% (95% CI 92·0-95·2), compared with 82·9% (80·0-85·5) for the HER2DX high-risk group, representing a 10·7% absolute difference (stratified HR 2·72, 95% CI 1·97-3·76; p<0·0001).

被分类为HER2DX低风险的患者6年无事件生存率为93.6%（95%置信区间92.0-95.2），而HER2DX高风险组为82.9%（80.0-85.5），绝对差异为10.7%（分层风险比2.72，95%置信区间1.97-3.76；p<0.0001）。

This association was consistent across subgroups, regardless of tumour stage, nodal stage, pathological complete response, or hormone receptor status.

这种关联在各个亚组中是一致的，无论肿瘤分期、淋巴结分期、病理完全缓解还是激素受体状态。

interpretation

HER2DX provides clinically meaningful prognostic stratification in early-stage HER2-positive breast cancer, beyond standard clinical-pathological variables and pathological response.

HER2DX 在早期 HER2 阳性乳腺癌中提供了超越标准临床病理变量和病理反应的临床意义重大的预后分层。

These results support its use in tailoring treatment intensity and guiding clinical decision making.

这些结果支持其在定制治疗强度和指导临床决策中的使用。

funding

Reveal Genomics.

揭示基因组学。