Molecular characterization of circulating tumor cells from patients with metastatic breast cancer reflects evolutionary changes in gene expression under the pressure of systemic therapy
| Autor: | Pär-Ola Bendahl, Kristina Aaltonen, Lisa Rydén, Anna Maria Larsson, Cecilia Graffman, Vendula Novosadova |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
0301 basic medicine estrogen receptor (ER) Pathology medicine.medical_specialty Receptor ErbB-2 Breast Neoplasms Kaplan-Meier Estimate circulating tumor cells 03 medical and health sciences 0302 clinical medicine Circulating tumor cell Breast cancer human epidermal growth factor receptor 2 (HER2) Gene expression Biomarkers Tumor Humans Medicine Neoplasm Metastasis Liquid biopsy skin and connective tissue diseases Aged Neoplasm Staging Aged 80 and over business.industry Gene Expression Profiling Cancer Middle Aged Neoplastic Cells Circulating medicine.disease Metastatic breast cancer Gene Expression Regulation Neoplastic Gene expression profiling 030104 developmental biology Receptors Estrogen Oncology Drug Resistance Neoplasm Tumor progression 030220 oncology & carcinogenesis gene expression Disease Progression Cancer research Female metastatic breast cancer Transcriptome business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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