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Clonality of circulating tumor cells in breast cancer brain metastasis patients

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Item Type:Article
Title:Clonality of circulating tumor cells in breast cancer brain metastasis patients
Creators Name:Riebensahm, C. and Joosse, S.A. and Mohme, M. and Hanssen, A. and Matschke, J. and Goy, Y. and Witzel, I. and Lamszus, K. and Kropidlowski, J. and Petersen, C. and Kolb-Kokocinski, A. and Sauer, S. and Borgmann, K. and Glatzel, M. and Müller, V. and Westphal, M. and Riethdorf, S. and Pantel, K. and Wikman, H.
Abstract:BACKGROUND: The incidence of brain metastases in breast cancer (BCBM) patients is increasing. These patients have a very poor prognosis, and therefore, identification of blood-based biomarkers, such as circulating tumor cells (CTCs), and understanding the genomic heterogeneity could help to personalize treatment options. METHODS: Both EpCAM-dependent (CellSearch® System) and EpCAM-independent Ficoll-based density centrifugation methods were used to detect CTCs from 57 BCBM patients. DNA from individual CTCs and corresponding primary tumors and brain metastases were analyzed by next-generation sequencing (NGS) in order to evaluate copy number aberrations and single nucleotide variations (SNVs). RESULTS: CTCs were detected after EpCAM-dependent enrichment in 47.7% of the patients (≥ 5 CTCs/7.5 ml blood in 20.5%). The CTC count was associated with ERBB2 status (p = 0.029) of the primary tumor as well as with the prevalence of bone metastases (p = 0.021). EpCAM-independent enrichment revealed CTCs in 32.6% of the patients, especially among triple-negative breast cancer (TNBC) patients (70.0%). A positive CTC status after enrichment of either method was significantly associated with decreased overall survival time (p < 0.05). Combining the results of both enrichment methods, 63.6% of the patients were classified as CTC positive. In three patients, the matched tumor tissue and single CTCs were analyzed by NGS showing chromosomal aberrations with a high genomic clonality and mutations in pathways potentially important in brain metastasis formation. CONCLUSION: The detection of CTCs, regardless of the enrichment method, is of prognostic relevance in BCBM patients and in combination with molecular analysis of CTCs can help defining patients with higher risk of early relapse and suitability for targeted treatment.
Keywords:CTC, Breast Cancer, Brain Metastases, Clonality, CNA, NGS, Chromosomal Aberrations
Source:Breast Cancer Research and Treatment
Page Range:101
Date:3 September 2019
Official Publication:https://doi.org/10.1186/s13058-019-1184-2
PubMed:View item in PubMed

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