Lara M Tretschock, Hannah Clemente, Katharina Smetanay, Carlo Fremd, Verena Thewes, Kathrin Haßdenteufel, Anna S Scholz, Klaus Pantel, Sabine Riethdorf, Andreas Trumpp, Andreas Schneeweiss, Laura Michel, Thomas M Deutsch
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引用次数: 0
Abstract
Introduction: Significant progress has been made in the targeted therapy of metastatic breast cancer (mBC) in recent years. In this context, new biomarkers enable personalized therapy management and individualized therapy monitoring. Therefore, the systemic treatment is based increasingly on the biological characteristics of the tumor disease. Given the challenges of obtaining fresh tumor tissue through biopsies, the significance of liquid biopsies for assessing circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) is of growing importance for the detection of prognostic and predictive biomarkers. Multiple studies have shown that the number of CTCs decreases under therapy, especially under anti-HER2-targeted therapy, and that the expression of the HER2 status on CTCs could play a role in predicting therapy response and therapeutic monitoring. The aim of this study was to analyze the HER2 status of CTCs in mBC patients before and after 3 months of systemic therapy to evaluate changes in the number of HER2 positive CTCs. The study focuses on HER2-low, which plays an increasingly important role in clinical practice due to new developments of HER2 targeting antibody drug conjugates (ADCs). In this context, temporal and spatial heterogeneity of the disease represent a major diagnostic challenge.
Methods: A total of 324 patients with complete immunohistochemistry (IHC) of biopsied metastases were divided into five groups: HER2 negative (-)/hormone receptor (HR) negative (-), HER2 -/HR positive (+), HER2 +/HR +/-, HER2-low/ HR + and HER2-low/ HR -. Before and after 3 months of a new therapeutic line for mBC, CTCs were enumerated and analyzed for HER2 expression using the Cell-Search® system. Overall survival of all subgroups was calculated.
Results: The analyses revealed a discrepancy between the HER2 status of CTCs and corresponding tumor tissues in 98 patients (30.2%). The number of CTCs in general and the number of HER2 + CTCs decreased during systemic treatment, mainly in HER2 + tumors, but also in the other subgroups.
Conclusions: Discrepancy in the HER2 status of the metastases and of CTCs was observed in approximately one third of patients. Measuring HER2 on CTCs could potentially offer a means to longitudinally monitor HER2 status during therapy and simultaneously address challenges such as tumor heterogeneity. Therefore, the predictive value of HER2 on CTCs should be further investigated in clinical trials.
期刊介绍:
With the first issue in 2014, the journal ''Onkologie'' has changed its title to ''Oncology Research and Treatment''. By this change, publisher and editor set the scene for the further development of this interdisciplinary journal. The English title makes it clear that the articles are published in English – a logical step for the journal, which is listed in all relevant international databases. For excellent manuscripts, a ''Fast Track'' was introduced: The review is carried out within 2 weeks; after acceptance the papers are published online within 14 days and immediately released as ''Editor’s Choice'' to provide the authors with maximum visibility of their results. Interesting case reports are published in the section ''Novel Insights from Clinical Practice'' which clearly highlights the scientific advances which the report presents.