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Updated: Sep 18, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC)
Anne Eckardt1, Ivonne Nel1, Laura Weydandt1
1Department of Gynecology, Medical Center, Leipzig University, 04103 Leipzig, Germany.
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.
Insights
Disseminated tumor cells (DTCs) in triple-negative breast cancer (TNBC) are linked to poor prognosis. Certain DTC profiles, like Vim+, Ki67+, and HER2+, may indicate a worse outcome and offer therapeutic targets.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Pathology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options.
- The characteristics and role of disseminated tumor cells (DTCs) in TNBC remain poorly understood.
- DTCs are associated with increased recurrence risk and poor prognosis in cancer patients.
Purpose of the Study:
- To investigate the characteristics of DTCs in patients with triple-negative breast cancer.
- To identify potential prognostic and therapeutic markers among DTC subpopulations.
- To explore the relationship between DTCs and treatment response in TNBC.
Main Methods:
- Analysis of bone marrow aspirates from 80 TNBC patients (primary and recurrent).
- Multi-parameter immunofluorescence staining for epithelial (Pan-CK), mesenchymal transition (vimentin), proliferation (Ki67), and therapy markers (HER2, PD-L1).
- Identification and characterization of DTC subpopulations and their correlation with clinical data.
Main Results:
- 56% of patients had detectable DTCs.
- 20 different DTC subpopulations were identified, with CK+Vim+Ki67+ being the most frequent.
- CK- DTCs correlated significantly with PD-L1 and HER2 negativity.
- DTC positivity, particularly CK- DTCs, was associated with poor response to neoadjuvant chemotherapy (NACT).
- DTCs positive for vimentin, Ki67, and HER2 were linked to worse prognosis.
Conclusions:
- DTC subpopulations expressing vimentin, Ki67, and HER2 are potential markers for poor prognosis in TNBC.
- These DTC profiles may represent therapeutically relevant targets.
- The study raises questions about DTC dormancy and chemotherapy persistence in TNBC.
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