Nicolò Eleonora, Serafini Mara Serena, Munoz-Arcos Laura, Pontolillo Letizia, Molteni Elisabetta, Bayou Nadia, Andreopoulou Eleni, Curigliano Giuseppe, Reduzzi Carolina, Cristofanilli Massimo
Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy.
Department of Oncology and Hematology-Oncology, University of Milan, Milan, Italy.
J Liq Biopsy. 2023 Oct 8;2:100117. doi: 10.1016/j.jlb.2023.100117. eCollection 2023 Dec.
The human epidermal growth factor receptor 2 (HER2) plays a central role in breast cancer (BC). Therefore, it is critical to develop a method that can capture its spatial and temporal heterogeneity. Nowadays, therapeutic decisions for BC patients relies on evaluation of HER2 status from tissue biopsies using immunohistochemistry and hybridization. Nevertheless, considering the technical and logistical challenges associated with tissue biopsies, there is an unmet need for a non-invasive and accurate approach to obtain assessment of HER2 status. In this context, circulating biomarkers, particularly circulating tumor cells (CTCs), emerged as promising candidates. HER2 assessment on CTCs can be performed at genomic, transcriptomic, and protein levels on both bulk CTCs and at the single-cell resolution. However, the main limitation of the literature to date is the lack of a consistent definition of HER2-positive CTCs, which poses a major challenge for both, future research and clinical applications. Several studies revealed discordance in HER2 status between the primary tumor and corresponding CTCs. For instance, HER2-positive CTCs have been detected among patients with HER2-negative BC and . As a result, researchers have evaluated the prognostic and predictive value of HER2 status in CTCs, both in the early and metastatic settings, to increase the possibility of using anti-HER2 therapy also for these patients and to dissect mechanisms of treatment resistance. This review aims to provide an overview of the methods to determine HER2 status in CTCs and to summarize the evidence and future perspective on how CTCs-HER2 assessment can be integrated into the clinical management of BC patients.
人表皮生长因子受体2（HER2）在乳腺癌（BC）中起着核心作用。因此，开发一种能够捕捉其时空异质性的方法至关重要。如今，BC患者的治疗决策依赖于通过免疫组织化学和杂交技术对组织活检样本进行HER2状态评估。然而，考虑到与组织活检相关的技术和后勤挑战，对于获得HER2状态的非侵入性准确评估方法仍存在未满足的需求。在这种背景下，循环生物标志物，特别是循环肿瘤细胞（CTC），成为有前景的候选者。可以在整体CTC以及单细胞分辨率水平上，在基因组、转录组和蛋白质水平对CTC进行HER2评估。然而，迄今为止文献的主要局限性在于缺乏对HER2阳性CTC的一致定义，这给未来研究和临床应用都带来了重大挑战。多项研究揭示了原发性肿瘤与相应CTC之间HER2状态的不一致性。例如，在HER2阴性BC患者中检测到了HER2阳性CTC。因此，研究人员评估了CTC中HER2状态在早期和转移阶段的预后和预测价值，以增加这些患者使用抗HER2治疗的可能性，并剖析治疗耐药机制。本综述旨在概述确定CTC中HER2状态的方法，并总结关于如何将CTC-HER2评估整合到BC患者临床管理中的证据和未来展望。
