Circulating tumor cells and breast cancer‑specific mutations in primary breast cancer

Mego, Michal; Karaba, Marián; Sedláčková, Tatiana; Benca, Juraj; Repiská, Gabriela; Krasnicanova, Lucia; Macuch, Jan; Sieberova, Gabriela; Jurišová, Silvia; Pinďák, Daniel; Kalavska, Katarína; Mardiak, Jozef; Minárik, Gabriel

doi:10.3892/mco.2020.2026

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…The main cause of death among BC patients is metastasis, where circulating tumor cells (CTCs) play a crucial role [ 2 ]. In fact, CTCs’ detection and enumeration have been reported in early as well as in metastatic BC and have been associated with poor clinical outcome (decreased PFS and OS) [ 3 , 4 ]. Epithelial markers, such as EpCAM or cytokeratins (CKs), have been widely used for the characterization of CTCs.…”

Section: Introductionmentioning

confidence: 99%

Immune Checkpoint and EMT-Related Molecules in Circulating Tumor Cells (CTCs) from Triple Negative Breast Cancer Patients and Their Clinical Impact

Vardas

Tolios

Christopoulou

et al. 2023

Cancers

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Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype. There are few targeted therapies for these patients, leading to an unmet need for new biomarkers. The present study aimed to investigate the expression of PD-L1, CTLA-4, GLU, and VIM in CTCs of TNBC patients. Ninety-five patients were enrolled in this study: sixty-four TNBC and thirty-one luminal. Of these patients, 60 were in the early stage, while 35 had metastatic disease. Protein expression was identified by immunofluorescence staining experiments and VyCAP analysis. All the examined proteins were upregulated in TNBC patients. The expression of the GLU+VIM+CK+ phenotype was higher (50%) in metastatic TNBC compared to early TNBC patients (17%) (p = 0.005). Among all the BC patients, a significant correlation was found between PD-L1+CD45−CK+ and CTLA-4+CD45−CK+ phenotypes (Spearman test, p = 0.024), implying an important role of dual inhibition in BC. Finally, the phenotypes GLU+VIM+CK+ and PD-L1+CD45−CK+ were associated with shorter OS in TNBC patients (OS: log-rank p = 0.048, HR = 2.9, OS: log-rank p < 0.001, HR = 8.7, respectively). Thus, PD-L1, CTLA-4, GLU, and VIM constitute significant biomarkers in TNBC associated with patients’ outcome, providing new therapeutic targets for this difficult breast cancer subtype.

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Section: Introductionmentioning

confidence: 99%

Immune Checkpoint and EMT-Related Molecules in Circulating Tumor Cells (CTCs) from Triple Negative Breast Cancer Patients and Their Clinical Impact

Vardas

Tolios

Christopoulou

et al. 2023

Cancers

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“…Furthermore, secretion of cathepsins by breast cancer cells has been shown to regulate neutrophils, enabling formation of metastatic niches in the lung [ 26 ]. EMT as well as modification of the extracellular matrix and peritumoral milieu have also been reported to be associated with increased tumor cell dissemination in breast cancer [ 27 , 28 ]. These findings may offer a molecular explanation for the association between high RS values and tumor cell dissemination into the BM.…”

Section: Discussionmentioning

confidence: 99%

Association between 21-gene-assay and detection of disseminated tumor cells in patients with early breast cancer: results from the IRMA trial

Volmer

Dannehl

Engler

et al. 2023

Breast Cancer Res Treat

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Purpose Disseminated tumor cells (DTCs) in the bone marrow (BM) are known to be of prognostic value for patients with early breast cancer (EBC). In addition to histopathological features, multigene expression assays, such as the commercially available 21-gene Breast Recurrence Score® assay, have been validated for evaluating prognosis and making decisions concerning adjuvant treatment in EBC. In a previous retrospective study from our group, the 21-gene assay was shown to be associated with DTC-detection. A secondary endpoint of the prospective IRMA trial was to evaluate the association between Recurrence Score® (RS) result and tumor cell dissemination in patients with EBC. Methods DTC-status and RS result were assessed in patients with ER-positive/HER2-negative EBC with 0–3 pathologic lymph nodes who underwent primary surgical treatment at the Department for Women’s Health of Tuebingen University, Germany. Results Patients with a high RS result (≥ 26) were more frequently DTC-positive (22.6%) than patients with a low RS result (8.6%, p = 0.034). The odds for DTC-positivity increased with rising RS values (p = 0.047). Conclusion We therefore confirm that a high genomic risk is associated with tumor cell dissemination into the BM. Further trials are needed to investigate whether therapeutic decisions could be further individualized by combining DTC-status and prognostic gene signature testing.

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“…Studies have shown that potential diagnostic biomarkers representing stemness [ 20 ], immunogenic CTC [ 18 ], and signaling molecules that promote breast cancer metastasis [ 19 ] are found in CTCs. The mutation and expression levels of breast cancer-associated genes such as BRCA 1/2 are also detectable by liquid biopsy [ 15 , 21 ].…”

Section: Breast Cancer and Circulating Tumor Cellsmentioning

confidence: 99%

Cellular Mechanisms of Circulating Tumor Cells During Breast Cancer Metastasis

Park

Brown

Kim

2020

IJMS

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Circulating tumor cells (CTCs) are cancer cells that detach from the primary site and travel in the blood stream. A higher number of CTCs increases the risk of breast cancer metastasis, and it is inversely associated with the survival rates of patients with breast cancer. Although the numbers of CTCs are generally low and the majority of CTCs die in circulation, the survival of a few CTCs can seed the development of a tumor at a secondary location. An increasing number of studies demonstrate that CTCs undergo modification in response to the dynamic biophysical environment in the blood due in part to fluid shear stress. Fluid shear stress generates reactive oxygen species (ROS), triggers redox-sensitive cell signaling, and alters the function of intracellular organelles. In particular, the mitochondrion is an important target organelle in determining the metastatic phenotype of CTCs. In healthy cells, mitochondria produce adenosine triphosphate (ATP) via oxidative phosphorylation in the electron transport chain, and during oxidative phosphorylation, they produce physiological levels of ROS. Mitochondria also govern death mechanisms such as apoptosis and mitochondrial permeability transition pore opening to, in order eliminate unwanted or damaged cells. However, in cancer cells, mitochondria are dysregulated, causing aberrant energy metabolism, redox homeostasis, and cell death pathways that may favor cancer invasiveness. In this review, we discuss the influence of fluid shear stress on CTCs with an emphasis on breast cancer pathology, then discuss alterations of cellular mechanisms that may increase the metastatic potentials of CTCs.

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Circulating tumor cells and breast cancer‑specific mutations in primary breast cancer

Cited by 6 publications

References 39 publications

Immune Checkpoint and EMT-Related Molecules in Circulating Tumor Cells (CTCs) from Triple Negative Breast Cancer Patients and Their Clinical Impact

Immune Checkpoint and EMT-Related Molecules in Circulating Tumor Cells (CTCs) from Triple Negative Breast Cancer Patients and Their Clinical Impact

Association between 21-gene-assay and detection of disseminated tumor cells in patients with early breast cancer: results from the IRMA trial

Cellular Mechanisms of Circulating Tumor Cells During Breast Cancer Metastasis

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