Abstract P2-11-16: Characterization of disseminated tumor cells (DTCs) in patients with triple-negative breast cancer (TNBC)

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Abstract Background: Despite successful treatment of the primary tumor, recurrence occurs in about 30% of breast cancer patients. One possible reason might be micro-metastases, so-called disseminated tumor cells (DTC) in the bone marrow (BM), which split off from the primary tumor in early stages of the disease. The most aggressive subtype is triple negative breast cancer (TNBC), which is hormone-receptor negative (<1% ER/ PR) and HER2 negative (IHC Score 0, 1 or 2 and CISH-). The majority of TNBCs are of high grade and show a high proliferation rate. Patients usually receive chemotherapy but have an increased risk of recurrence and poor prognosis. Particularly patients that do not achieve pathological complete remission (pCR) after chemotherapy might require targeted treatment approaches. Little is known concerning the characteristics of DTCs and their role in TNBC patients. Methods: BM aspirates were collected from the anterior iliac crest of 80 patients with primary (n=67) or recurrent (n=13) TNBC during surgery. After density gradient centrifugation, cell suspensions were transferred onto glass slides and subjected to a sequential multi-parameter immunofluorescence staining procedure, detecting pan-cytokeratin (CK), vimentin (vim), and for exclusion of hematopoietic cells CD45 in a first panel. Cells were digitalized and detected using the Zeiss Axioscan 7 scannig microscope. After enzymatic release of the fluorochromes, a second antibody panel including HER2, Ki67 and PD-L1 was applied to the same slides, followed by scanning and detection. Nuclei were identified using DAPI within the mounting media in both staining steps. We analyzed 2 x 106 cells per patient. Results: The DTC positive rate was 56% (n=45) among the cohort. In total, we detected 253 DTCs resulting in a median number of 4 DTCs per patient. Of the 64 patients treated with NACT, 35 were DTC positive and had a decreased pCR rate (54%) compared to DTC negative patients (n=29; pCR rate: 69%). Concerning epithelial-to-mesenchymal transition, phenotype characterization revealed that 14 patients showed epithelial DTCs (CK+/Vim-) only, 45 cases had epithelial (CK+/Vim-) as well as mesenchymal (CK-/vim+) DTCs and DTCs with mixed characteristics (CK+/vim+). One patient displayed mesenchymal DTCs only (CK-). Based on the phenotypical (panel 1) and therapeutic (panel 2) marker expressions, we found 20 different DTC subpopulations. The majority of epithelial DTCs (CK+/vim-) revealed no expression of PD-L1, Ki67 or HER2 (68%). However, DTCs with hybrid characteristics (CK+/vim+) displayed increased numbers of Ki67+ (85%) and PD-L1+/Ki67+ DTCs (30%). The most frequently occurring profile was CK+/vim+/PD-L1-/ Ki67+/ HER2- (n=75 cells). Interestingly, the mesenchymal DTCs (CK-/vim+) revealed elevated DTC numbers with PD-L1+/Ki67+/HER2± (45%) which increased up to 80% in the CK-/vim- DTCs. HER2 positive cells were predominantly found in non-epithelial DTCs (CK-). Conclusion: Our data indicate that the process of EMT might be linked to the occurrence of DTC subpopulations positive for Ki67, PD-L1 and HER2 which could be therapeutically relevant. Further, our results rise the question whether DTCs are dormant in TNBC patients. Citation Format: Anne Eckardt, Laura Weydandt, Annekathrin Höhn, Bahriye Aktas, Ivonne Nel. Characterization of disseminated tumor cells (DTCs) in patients with triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-11-16.

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