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Open AccessArticle

Impact of mRNA-Assessed Molecular Subtype Conversion, Intact and Apoptotic Circulating Tumor Cells on Survival of Metastatic Breast Cancer Patients: Proof of Principle

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Department of Gynecology and Obstetrics, Mannheim University Hospital, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
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Department of Gynecology and Obstetrics, Heidelberg University Hospital, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany
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Stratifyer Molecular Pathology GmbH, Werthmannstr. 1c, 50935 Cologne, Germany
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Department of Women’s Health, University Hospital Tübingen, Calwerstr. 7, 72076 Tübingen, Germany
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Department of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany
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Department of Hematology and Immunology, Clinical Center of Nis, University of Nis, Bulevar Zorana Djindjica 48, 18000 Nis, Serbia
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National Center for Tumor Diseases (NCT) Heidelberg, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany
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German Cancer Research Center (DKFZ), Heidelberg, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
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Author to whom correspondence should be addressed.
Diagnostics 2020, 10(6), 369; https://doi.org/10.3390/diagnostics10060369
Received: 18 April 2020 / Revised: 31 May 2020 / Accepted: 1 June 2020 / Published: 4 June 2020
(This article belongs to the Section Pathology and Molecular Diagnostics)
Breast cancers (BC) can mutate, allowing metastatic tumors (MT) to sometimes differ to primary tumors (PT) in gene expression. Despite contemporary metastatic breast cancer (MBC) therapy, subtype conversion seems prognostically disadvantageous. We strived to determine the influence of mRNA-assessed intrinsic subtype stability comparing PT and MT biopsies and circulating tumor cell (CTC)-based liquid biopsies on progression free survival (PFS) and overall survival (OS). Additional analyzed prognostic factors were PT subtype, MT subtype and hormone receptor loss. Kaplan-Meier curves and the log rank tests were used to compare PFSs and OSs. The proportions of luminal B and triple negative subtype MTs were increased compared to those observed in PTs. Fifteen patients were found to have tumors that underwent intrinsic subtype conversion and their OS was significantly decreased (p = 0.038). No such difference was observed when it comes to PFS. The majority of these tumors switched to a more aggressive intrinsic subtype. No significant differences in PFSs or OSs were observed between subtype converters with triple negative PTs compared to those with luminal subtype PTs. The same is true of subtype stable patients. Total CTC, iCTC and aCTC counts decreased with therapy, but there were no significant differences between subtype converters and subtype stable patients. Our data confirm a poorer overall survival of the intrinsic subtype converters and emphasize the importance of acquiring biopsies and re-biopsies of all available metastatic lesions alongside with CTC-based liquid biopsies for earlier recognition of patients with poorer prognosis and in need of altered individualized therapy regimens. View Full-Text
Keywords: breast cancer; circulating tumor cells; intrinsic subtype; biomarker conversion; survival; RT-qPCR breast cancer; circulating tumor cells; intrinsic subtype; biomarker conversion; survival; RT-qPCR
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Stefanovic, S.; Deutsch, T.M.; Wirtz, R.; Hartkopf, A.; Sinn, P.; Kohler, M.; Hofmann, J.; Bankovic, S.; Vassilev, K.; Sütterlin, M.; Schneeweiss, A.; Wallwiener, M. Impact of mRNA-Assessed Molecular Subtype Conversion, Intact and Apoptotic Circulating Tumor Cells on Survival of Metastatic Breast Cancer Patients: Proof of Principle. Diagnostics 2020, 10, 369.

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