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Cancers
Volume 11
Issue 3
10.3390/cancers11030342
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Article

Molecular Subtype Conversion between Primary and Metastatic Breast Cancer Corresponding to the Dynamics of Apoptotic and Intact Circulating Tumor Cells

by
Stefan Stefanovic
1,*,
Thomas M. Deutsch
2,
Ralph Wirtz
3,
Andreas Hartkopf
4,
Peter Sinn
5,
Florian Schuetz
2,
Christof Sohn
2,
Michael K. Bohlmann
1,
Marc Sütterlin
1,
Andreas Schneeweiss
2,6 and
Markus Wallwiener
2
1
Department of Gynecology and Obstetrics, Mannheim University Hospital, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
2
Department of Gynecology and Obstetrics, Heidelberg University Hospital, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany
3
Stratifyer Molecular Pathology GmbH, Werthmannstr. 1c, 50935 Cologne, Germany
4
Department of Women’s Health, University Hospital Tübingen, Calwerstr. 7, 72076 Tübingen, Germany
5
Department of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany
6
National Center for Tumor Diseases (NCT) Heidelberg, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(3), 342; https://doi.org/10.3390/cancers11030342
Submission received: 25 February 2019 / Accepted: 5 March 2019 / Published: 11 March 2019
(This article belongs to the Special Issue Liquid Biopsy for Cancer)
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Abstract

The presence of circulating tumor cells (CTCs), detected as a form of liquid biopsy is associated with poor survival in both early and metastatic breast cancer. Monitoring tumor biology based on intrinsic subtypes delivers treatment-relevant information on the heterogeneity or biomarker conversion between primary and metastatic tumors. This study aimed to correlate the change of the apoptotic and intact CTC counts with mRNA-assessed intrinsic subtype change. Thirty-four breast cancer patients with available triplets of primary tumors, distant metastasis biopsies and data on intact and apoptotic CTC dynamics were included in the analysis. The intrinsic subtype was determined per RT-qPCR quantification of the gene expression ESR1, PGR, ERBB2 and MKI67. Both luminal (p = 0.038) and triple negative (p = 0.035) patients showed a significant downregulation of apoptotic CTCs. Repeated biopsies of distant metastatic sites, as well as determining a potential shift of the intrinsic subtype, combined with data on intact and apoptotic CTC dynamics from liquid biopsies might help personalize systemic therapy and generate additional surrogate markers for successful systemic therapy.
Keywords: breast cancer; intrinsic subtype; biomarker conversion; circulating tumor cells; RT-qPCR breast cancer; intrinsic subtype; biomarker conversion; circulating tumor cells; RT-qPCR

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MDPI and ACS Style

Stefanovic, S.; Deutsch, T.M.; Wirtz, R.; Hartkopf, A.; Sinn, P.; Schuetz, F.; Sohn, C.; Bohlmann, M.K.; Sütterlin, M.; Schneeweiss, A.; et al. Molecular Subtype Conversion between Primary and Metastatic Breast Cancer Corresponding to the Dynamics of Apoptotic and Intact Circulating Tumor Cells. Cancers 2019, 11, 342. https://doi.org/10.3390/cancers11030342

AMA Style

Stefanovic S, Deutsch TM, Wirtz R, Hartkopf A, Sinn P, Schuetz F, Sohn C, Bohlmann MK, Sütterlin M, Schneeweiss A, et al. Molecular Subtype Conversion between Primary and Metastatic Breast Cancer Corresponding to the Dynamics of Apoptotic and Intact Circulating Tumor Cells. Cancers. 2019; 11(3):342. https://doi.org/10.3390/cancers11030342

Chicago/Turabian Style

Stefanovic, Stefan, Thomas M. Deutsch, Ralph Wirtz, Andreas Hartkopf, Peter Sinn, Florian Schuetz, Christof Sohn, Michael K. Bohlmann, Marc Sütterlin, Andreas Schneeweiss, and et al. 2019. "Molecular Subtype Conversion between Primary and Metastatic Breast Cancer Corresponding to the Dynamics of Apoptotic and Intact Circulating Tumor Cells" Cancers 11, no. 3: 342. https://doi.org/10.3390/cancers11030342

APA Style

Stefanovic, S., Deutsch, T. M., Wirtz, R., Hartkopf, A., Sinn, P., Schuetz, F., Sohn, C., Bohlmann, M. K., Sütterlin, M., Schneeweiss, A., & Wallwiener, M. (2019). Molecular Subtype Conversion between Primary and Metastatic Breast Cancer Corresponding to the Dynamics of Apoptotic and Intact Circulating Tumor Cells. Cancers, 11(3), 342. https://doi.org/10.3390/cancers11030342

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