Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China; Breast Cancer Institute, Fujian Medical University, Fuzhou, Fujian Province, China.
Genesky Biotechnologies Inc., Shanghai, 201315, China.
Breast. 2022 Apr;62:114-122. doi: 10.1016/j.breast.2022.02.002. Epub 2022 Feb 8.
The quantitative relationship between HER2 copy number and prognosis in HER2 positive adjuvant setting remain controversial, and few studies have focused on adjuvant setting to illustrate the potential clinical relevance of HER2 in cfDNA. Our study aim to develop a novel method in HER2 quantification and explore the relationship between HER2 copy number in primary tumors or cfDNA and prognosis in HER2 positive early breast cancer.
Two hundred and two patients with early breast cancer were prospectively included in a study where primary tumors, matching non-cancer breast tissue, corresponding plasma, and the plasma from 20 healthy volunteers were collected. Cox proportional hazard analysis was employed to determine the prognostic value of HER2 gene copy number in tissue and cfDNA. Tissue based nomograms and time-dependent decision curve analysis were used to evaluate the practicality of HER2 copy number stratification.
HER2 amplification by CNVplex demonstrated a robust concordance with FISH (concordance 89.2%). A three-tiered system of tissue and a two-tiered system of cfDNA classification were shown to be independent prognostic factors. A tissue copy number-based nomogram was fitted and further evaluation revealed a good performance in discrimination (c statistic 0.801) and calibration.
We first report CNVplex as a viable alternative for HER2 detection. Quantitative evaluation of HER2 presents tremendous potential for use in risk stratification. We also uncover the potential for using HER2 copy number in cfDNA as a biomarker for prognosis in a HER2 positive adjuvant setting.
HER2 拷贝数与 HER2 阳性辅助治疗中的预后之间的定量关系仍存在争议，很少有研究关注辅助治疗中 HER2 在 cfDNA 中的潜在临床相关性。我们的研究旨在开发一种新的 HER2 定量方法，并探讨原发肿瘤或 cfDNA 中的 HER2 拷贝数与 HER2 阳性早期乳腺癌预后之间的关系。
前瞻性纳入 202 例早期乳腺癌患者，收集其原发肿瘤、匹配的非癌乳腺组织、相应的血浆以及 20 名健康志愿者的血浆。采用 Cox 比例风险分析确定组织和 cfDNA 中 HER2 基因拷贝数的预后价值。组织基列线图和时间依赖性决策曲线分析用于评估 HER2 拷贝数分层的实用性。
CNVplex 检测的 HER2 扩增与 FISH 具有良好的一致性（一致性 89.2%）。三分类组织和二分类 cfDNA 分类系统均为独立的预后因素。建立了组织拷贝数的列线图，进一步评估显示其在鉴别能力（c 统计量 0.801）和校准方面表现良好。
我们首次报道了 CNVplex 作为一种可行的 HER2 检测替代方法。HER2 的定量评估在风险分层中有很大的应用潜力。我们还发现，cfDNA 中的 HER2 拷贝数可能成为 HER2 阳性辅助治疗中预后的生物标志物。
