Real-time assessment of HER2 status in circulating tumor cells of breast cancer patients: Methods of detection and clinical implications

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 biops...

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Main Authors: Eleonora Nicolò, Mara Serena Serafini, Laura Munoz-Arcos, Letizia Pontolillo, Elisabetta Molteni, Nadia Bayou, Eleni Andreopoulou, Giuseppe Curigliano, Carolina Reduzzi, Massimo Cristofanilli
Format: Article
Language:English
Published: Elsevier 2023-12-01
Series:The Journal of Liquid Biopsy
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Online Access:http://www.sciencedirect.com/science/article/pii/S2950195423001170
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author Eleonora Nicolò
Mara Serena Serafini
Laura Munoz-Arcos
Letizia Pontolillo
Elisabetta Molteni
Nadia Bayou
Eleni Andreopoulou
Giuseppe Curigliano
Carolina Reduzzi
Massimo Cristofanilli
author_facet Eleonora Nicolò
Mara Serena Serafini
Laura Munoz-Arcos
Letizia Pontolillo
Elisabetta Molteni
Nadia Bayou
Eleni Andreopoulou
Giuseppe Curigliano
Carolina Reduzzi
Massimo Cristofanilli
author_sort Eleonora Nicolò
collection DOAJ
description 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 in situ 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 real-time 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 vice versa. 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.
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spelling doaj-art-89eab89b25b84e08a2924abb642ee2ea2024-11-22T07:41:23ZengElsevierThe Journal of Liquid Biopsy2950-19542023-12-012100117Real-time assessment of HER2 status in circulating tumor cells of breast cancer patients: Methods of detection and clinical implicationsEleonora Nicolò0Mara Serena Serafini1Laura Munoz-Arcos2Letizia Pontolillo3Elisabetta Molteni4Nadia Bayou5Eleni Andreopoulou6Giuseppe Curigliano7Carolina Reduzzi8Massimo Cristofanilli9Division 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; Department of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY, USA; Corresponding author. Department of Medicine Division of Hematology-Oncology, 1300 York Avenue, New York, NY, 10065, USA.Department of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY, USADepartment of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY, USADepartment of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY, USA; Medical Oncology Department, Catholic University of Sacred Heart, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyDepartment of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY, USA; Department of Medicine, University of Udine, Via Chiusaforte, Udine, ItalyDepartment of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY, USA; Human Genetics Laboratory (LR99ES10), Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, 2092, TunisiaDepartment of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY, USADivision of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Hematology-Oncology, University of Milan, Milan, ItalyDepartment of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY, USADepartment of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY, USAThe 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 in situ 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 real-time 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 vice versa. 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.http://www.sciencedirect.com/science/article/pii/S2950195423001170Circulating tumor cellsBreast cancerHER2HER2-LowPrognostic valuePredictive value
spellingShingle Eleonora Nicolò
Mara Serena Serafini
Laura Munoz-Arcos
Letizia Pontolillo
Elisabetta Molteni
Nadia Bayou
Eleni Andreopoulou
Giuseppe Curigliano
Carolina Reduzzi
Massimo Cristofanilli
Real-time assessment of HER2 status in circulating tumor cells of breast cancer patients: Methods of detection and clinical implications
The Journal of Liquid Biopsy
Circulating tumor cells
Breast cancer
HER2
HER2-Low
Prognostic value
Predictive value
title Real-time assessment of HER2 status in circulating tumor cells of breast cancer patients: Methods of detection and clinical implications
title_full Real-time assessment of HER2 status in circulating tumor cells of breast cancer patients: Methods of detection and clinical implications
title_fullStr Real-time assessment of HER2 status in circulating tumor cells of breast cancer patients: Methods of detection and clinical implications
title_full_unstemmed Real-time assessment of HER2 status in circulating tumor cells of breast cancer patients: Methods of detection and clinical implications
title_short Real-time assessment of HER2 status in circulating tumor cells of breast cancer patients: Methods of detection and clinical implications
title_sort real time assessment of her2 status in circulating tumor cells of breast cancer patients methods of detection and clinical implications
topic Circulating tumor cells
Breast cancer
HER2
HER2-Low
Prognostic value
Predictive value
url http://www.sciencedirect.com/science/article/pii/S2950195423001170
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