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.

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

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

Department of Surgery Skåne University Hospital Malmö Sweden

Department of Translational Cancer Research Lund University Lund Sweden

Institute of Biotechnology BIOCEV Centre Czech Academy of Sciences Vestec u Prahy Czech Republic

Skåne Department of Oncology Skåne University Hospital Lund Sweden

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Recent Advances in Methods for Circulating Tumor Cell Detection