Background/Objectives: Breast cancer is the most commonly diagnosed cancer worldwide, with high rates of distant metastasis. While circulating tumor cells (CTCs) are the disseminatory units of metastasis and are indicative of a poor prognosis, CTC heterogeneity within individual patients, among breast cancer subtypes, and between primary and metastatic tumors within a patient obscures the relationship between CTCs and disease progression. EpCAM, its homolog Trop2, and a pan-Cytokeratin marker were evaluated to determine their contributions to CTC presence and clustering over the study period. We conducted a systematic longitudinal analysis of 51 breast cancer patients during the course of their treatment to deepen our understanding of CTC contributions to breast cancer progression.Methods: 272 total blood samples from 51 metastatic breast cancer (mBC) patients were included in the study. Patients received diverse treatment schedules based on discretion of the practicing oncologist. Patients were monitored from July 2020 to March 2023, with blood samples collected at scheduled care appointments. Nucleated cells were isolated, imaged, and analyzed using Rarecyte®technology, and statistical analysis was performed in R using the lmerTest and lme4 packages, as well as in Graphpad Prism version 10.4.1.Results: Both classical CTCs (DAPI+, EpCAM+, CK+, CD45– cells) and Trop2+ CTCs were detected in the blood of breast cancer patients. A high degree of correlation was found between CTC biomarkers, and CTC expression of EpCAM, Trop2, and the presence of CD45+ cells, all predicted cluster size, while Pan-CK did not. Furthermore, while analyses of biomarkers by receptor status revealed no significant differences among HR+, HER2+, and TNBC patients, longitudinal analysis found evidence for discrete trajectories of EpCAM, Trop2, and clustering between HR+ and HER2+ cancers after diagnosis of metastasis.Conclusions: Correlation and longitudinal analysis revealed that EpCAM+, Trop2+, and CD45+ cells were predictive of CTC cluster presence and size, and highlighted distinct trajectories of biomarker change over time between HR+ and HER2+ cancers following metastatic diagnosis.
背景/目的：乳腺癌是全球最常见的恶性肿瘤，其远处转移率较高。循环肿瘤细胞（CTCs）作为肿瘤转移的播散单元，通常提示不良预后。然而，患者个体内CTC的异质性、不同乳腺癌亚型间的差异以及同一患者原发灶与转移灶之间的异质性，使得CTC与疾病进展的关系难以明确。本研究通过评估上皮细胞黏附分子（EpCAM）、其同源蛋白Trop2及广谱细胞角蛋白标志物，旨在探究这些标志物在研究期间对CTC存在及聚集的贡献。我们对51例乳腺癌患者治疗过程进行了系统性纵向分析，以深化对CTC在乳腺癌进展中作用的理解。 方法：本研究纳入51例转移性乳腺癌（mBC）患者的272份血液样本。患者治疗方案由临床肿瘤医生根据个体情况制定。监测周期为2020年7月至2023年3月，血液样本在定期随访时采集。采用Rarecyte®技术分离、成像并分析有核细胞，使用R语言中的lmerTest和lme4软件包以及Graphpad Prism 10.4.1版本进行统计分析。 结果：在乳腺癌患者血液中检测到经典CTC（DAPI+、EpCAM+、CK+、CD45–细胞）和Trop2+ CTC。CTC生物标志物间呈现高度相关性，其中EpCAM、Trop2的表达水平及CD45+细胞的存在均能预测CTC团簇大小，而广谱细胞角蛋白（Pan-CK）无此预测作用。进一步分析显示，虽然不同受体状态（HR+、HER2+、三阴性乳腺癌）患者的生物标志物未见显著差异，但纵向分析发现HR+与HER2+乳腺癌患者在发生转移后，其EpCAM、Trop2表达及CTC聚集呈现不同的动态演变轨迹。 结论：相关性及纵向分析表明，EpCAM+、Trop2+及CD45+细胞对CTC团簇的存在和大小具有预测价值，并揭示了HR+与HER2+乳腺癌在转移诊断后生物标志物随时间变化的差异性轨迹。
肿瘤(癌症)患者之家