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

Aaltonen, Kristina E. LU ; Novosadová, Vendula; Bendahl, Pär Ola LU ; Graffman, Cecilia LU ; Larsson, Anna Maria LU and Rydén, Lisa LU (2017) In Oncotarget 8(28). p.45544-45565
Abstract

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... (More)

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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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Circulating tumor cells, Estrogen receptor (ER), Gene expression, Human epidermal growth factor receptor 2 (HER2), Metastatic breast cancer
in
Oncotarget
volume
8
issue
28
pages
22 pages
publisher
Impact Journals, LLC
external identifiers
  • scopus:85022190280
  • wos:000405504600049
ISSN
1949-2553
DOI
10.18632/oncotarget.17271
language
English
LU publication?
yes
id
608e05cb-0815-4aec-99dd-964ccf45c929
date added to LUP
2017-08-22 10:12:33
date last changed
2017-09-18 11:42:27
@article{608e05cb-0815-4aec-99dd-964ccf45c929,
  abstract     = {<p>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.</p>},
  author       = {Aaltonen, Kristina E. and Novosadová, Vendula and Bendahl, Pär Ola and Graffman, Cecilia and Larsson, Anna Maria and Rydén, Lisa},
  issn         = {1949-2553},
  keyword      = {Circulating tumor cells,Estrogen receptor (ER),Gene expression,Human epidermal growth factor receptor 2 (HER2),Metastatic breast cancer},
  language     = {eng},
  number       = {28},
  pages        = {45544--45565},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Molecular characterization of circulating tumor cells from patients with metastatic breast cancer reflects evolutionary changes in gene expression under the pressure of systemic therapy},
  url          = {http://dx.doi.org/10.18632/oncotarget.17271},
  volume       = {8},
  year         = {2017},
}