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Breast Cancer Research
Published in: Breast Cancer Research 1/2019

Open Access 01-12-2019 | Metastasis | Research article

Clonality of circulating tumor cells in breast cancer brain metastasis patients

Authors: Carlotta Riebensahm, Simon A. Joosse, Malte Mohme, Annkathrin Hanssen, Jakob Matschke, Yvonne Goy, Isabell Witzel, Katrin Lamszus, Jolanthe Kropidlowski, Cordula Petersen, Anja Kolb-Kokocinski, Sascha Sauer, Kerstin Borgmann, Markus Glatzel, Volkmar Müller, Manfred Westphal, Sabine Riethdorf, Klaus Pantel, Harriet Wikman

Published in: Breast Cancer Research | Issue 1/2019

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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.
Appendix
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Metadata
Title
Clonality of circulating tumor cells in breast cancer brain metastasis patients
Authors
Carlotta Riebensahm
Simon A. Joosse
Malte Mohme
Annkathrin Hanssen
Jakob Matschke
Yvonne Goy
Isabell Witzel
Katrin Lamszus
Jolanthe Kropidlowski
Cordula Petersen
Anja Kolb-Kokocinski
Sascha Sauer
Kerstin Borgmann
Markus Glatzel
Volkmar Müller
Manfred Westphal
Sabine Riethdorf
Klaus Pantel
Harriet Wikman
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2019
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-019-1184-2

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