Research Papers:

Molecular characterization of circulating tumor cells from patients with metastatic breast cancer reflects evolutionary changes in gene expression under the pressure of systemic therapy

Kristina E. Aaltonen _, Vendula Novosadová, Pär-Ola Bendahl, Cecilia Graffman, Anna-Maria Larsson and Lisa Rydén

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Oncotarget. 2017; 8:45544-45565. https://doi.org/10.18632/oncotarget.17271

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Kristina E. Aaltonen1, Vendula Novosadová2, Pär-Ola Bendahl1, Cecilia Graffman3, Anna-Maria Larsson3,4 and Lisa Rydén5,6

1Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden

2Institute of Biotechnology, BIOCEV Centre, Czech Academy of Sciences, Vestec, Czech Republic

3Skåne Department of Oncology, Skåne University Hospital, Lund, Sweden

4Department of Translational Cancer Research, Lund University, Lund, Sweden

5Department of Clinical Sciences Lund, Division of Surgery, Lund University, Lund, Sweden

6Department of Surgery, Skåne University Hospital, Malmö, Sweden

Correspondence to:

Kristina E. Aaltonen, email: [email protected]

Keywords: metastatic breast cancer, circulating tumor cells, gene expression, human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER)

Received: November 10, 2016    Accepted: March 30, 2017    Published: April 20, 2017


Resistance to systemic therapy is a major problem in metastatic breast cancer (MBC) that can be explained by initial tumor heterogeneity as well as by evolutionary changes during therapy and tumor progression. Circulating tumor cells (CTCs) detected in a liquid biopsy can be sampled and characterized repeatedly during therapy in order to monitor treatment response and disease progression.

Our aim was to investigate how CTC derived gene expression of treatment predictive markers (ESR1/HER2) and other cancer associated markers changed in patient blood samples during six months of first-line systemic treatment for MBC. CTCs from 36 patients were enriched using CellSearch (Janssen Diagnostics) and AdnaTest (QIAGEN) before gene expression analysis was performed with a customized gene panel (TATAA Biocenter).

Our results show that antibodies against HER2 and EGFR were valuable to isolate CTCs unidentified by CellSearch and possibly lacking EpCAM expression. Evaluation of patients with clinically different breast cancer subgroups demonstrated that gene expression of treatment predictive markers changed over time. This change was especially prominent for HER2 expression.

In conclusion, we found that changed gene expression during first-line systemic therapy for MBC could be a possible explanation for treatment resistance. Characterization of CTCs at several time-points during therapy could be informative for treatment selection.

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