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HER2(-Low) Expression on Circulating Tumor Cells and Corresponding Metastatic Tissue in Metastatic Breast Cancer
Lara M Tretschock1, Hannah Clemente1, Katharina Smetanay1
1Heidelberg University Women's Hospital, Heidelberg, Germany.
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 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. In this context, temporal and spatial heterogeneity of the disease represent a major diagnostic challenge.
Methods:
A total of 324 patients with complete immunohistochemistry 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 CellSearch® 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.
Insights
Liquid biopsies reveal discrepancies in HER2 status between circulating tumor cells (CTCs) and tumor tissue in metastatic breast cancer (mBC). Monitoring HER2 on CTCs may offer insights into therapy response and heterogeneity.
Area of Science:
- Oncology
- Molecular Diagnostics
- Biomarker Discovery
Background:
- Metastatic breast cancer (mBC) treatment advances with personalized therapies based on tumor biomarkers.
- Liquid biopsies, analyzing circulating tumor cells (CTCs) and DNA, are crucial for monitoring due to biopsy challenges.
- HER2 status in CTCs is increasingly important for predicting therapy response and monitoring treatment.
Purpose of the Study:
- To analyze HER2 status in CTCs of mBC patients before and after 3 months of systemic therapy.
- To evaluate changes in the number of HER2-positive CTCs and their correlation with HER2-low status.
- To address diagnostic challenges posed by tumor heterogeneity in mBC.
Main Methods:
- 324 mBC patients with complete immunohistochemistry of biopsied metastases were categorized into five HER2/HR groups.
- Circulating tumor cells (CTCs) were enumerated and analyzed for HER2 expression using CellSearch® before and after 3 months of therapy.
- Overall survival was calculated for all patient subgroups.
Main Results:
- A HER2 status discrepancy between CTCs and tumor tissue was observed in 30.2% of patients.
- Systemic treatment led to a decrease in both total CTCs and HER2-positive CTCs across most subgroups.
- The reduction in CTCs was most pronounced in HER2-positive tumors but also evident in other subgroups.
Conclusions:
- Approximately one-third of patients showed a discrepancy in HER2 status between metastases and CTCs.
- Measuring HER2 on CTCs offers a potential method for longitudinal monitoring of HER2 status during therapy.
- Further clinical trials are warranted to investigate the predictive value of HER2 on CTCs, especially concerning tumor heterogeneity.
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