Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC)

Eckardt, Anne; Nel, Ivonne; Weydandt, Laura; Brochwitz, Elisa; Höhn, Anne Kathrin; Winter, Karsten; Aktas, Bahriye

doi:10.3390/cells14120857

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Open AccessArticle

Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC)

by

Anne Eckardt

^1,†,

Ivonne Nel

^1,*,†,

Laura Weydandt

¹

,

Elisa Brochwitz

¹,

Anne Kathrin Höhn

²,

Karsten Winter

³ and

Bahriye Aktas

¹

Department of Gynecology, Medical Center, Leipzig University, 04103 Leipzig, Germany

²

Department of Pathology, Medical Center, Leipzig University, 04103 Leipzig, Germany

³

Institute of Anatomy, Medical Faculty, Leipzig University, 04103 Leipzig, Germany

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Cells 2025, 14(12), 857; https://doi.org/10.3390/cells14120857

Submission received: 15 April 2025 / Revised: 2 June 2025 / Accepted: 3 June 2025 / Published: 6 June 2025

(This article belongs to the Special Issue How Can We Optimise Cancer Therapy? Tumour Microenvironment and Immune Evasion Strategies)

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Abstract

Triple negative breast cancer (TNBC) is the most aggressive molecular subtype and it lacks targetable receptors. Patients have an increased risk of recurrence and poor prognosis. Little is known concerning the characteristics of disseminated tumor cells (DTCs) and their role in TNBC patients. We analyzed the bone marrow aspirates of 80 patients with primary (n = 67) or recurrent (n = 13) TNBC, using a multi-parameter immunofluorescence staining procedure, including Pan-CK as an epithelial marker, vimentin (vim) as a marker of epithelial–mesenchymal transition, Ki67 for cell proliferation, and HER2 as well as PD-L1 as therapy-related markers. The DTC positive rate was 56% (n= 45) among the cohort. We found 20 different DTC subpopulations. The most frequently detected profile was CK+Vim+Ki67+ (n = 75 cells). The occurrence of CK- DTCs (n = 69) was significantly correlated to PD-L1 (r = −0.305, p < 0.01) and HER2 positivity (r = −0.234, p < 0.001). DTC positive patients that received neoadjuvant chemotherapy (NACT) and did not reach pathologic complete response were more likely to have CK- DTCs. Our data indicate that the occurrence of DTC subpopulations positive for Vim, Ki67, and HER2 appear to be markers for bad prognosis and could be therapeutically relevant. Furthermore, our results raise the question of whether DTCs are dormant in TNBC patients and persistent towards chemotherapy.

Keywords: triple negative; breast cancer (TNBC); disseminated tumor cells (DTCs); bone marrow; neoadjuvant chemotherapy; pathologic complete remission (pCR); Ki67; HER2; PD-L1

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MDPI and ACS Style

Eckardt, A.; Nel, I.; Weydandt, L.; Brochwitz, E.; Höhn, A.K.; Winter, K.; Aktas, B. Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC). Cells 2025, 14, 857. https://doi.org/10.3390/cells14120857

AMA Style

Eckardt A, Nel I, Weydandt L, Brochwitz E, Höhn AK, Winter K, Aktas B. Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC). Cells. 2025; 14(12):857. https://doi.org/10.3390/cells14120857

Chicago/Turabian Style

Eckardt, Anne, Ivonne Nel, Laura Weydandt, Elisa Brochwitz, Anne Kathrin Höhn, Karsten Winter, and Bahriye Aktas. 2025. "Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC)" Cells 14, no. 12: 857. https://doi.org/10.3390/cells14120857

APA Style

Eckardt, A., Nel, I., Weydandt, L., Brochwitz, E., Höhn, A. K., Winter, K., & Aktas, B. (2025). Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC). Cells, 14(12), 857. https://doi.org/10.3390/cells14120857

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Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC)

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