The presence of various populations of circulating tumor cells in the blood of breast cancer patients before treatment: association with five-year metastasis-free survival
Localized and metastatic tumors are known to lead to the formation of circulating tumor cell (CTC) clusters in the blood. Currently, there is a heightened interest in the study of molecular and biological characteristics of CTCs. Recent studies have shown the presence of different populations of CTCs in the blood of cancer patients. Some cells are cancer stem cells, some tumor cells undergo epithelial-mesenchymal transition (EMT), and most CTCs do not have features of either stem cells or EMT. The aim of the study was to evaluate the five-year metastasis-free survival rate in patients with invasive breast carcinoma, depending on the presence of various populations of circulating tumor cells in the blood before treatment. Material and Methods. A prospective study included 47 patients with newly diagnosed invasive breast cancer (T1-4N0-3M0), who were treated at Cancer Research institute, Tomsk National Research Medical Center. The patients aged 31 to 69 years. The presence of different populations of CTCs in the blood of patients before treatment was determined by multicolor flow cytometry on the BD FACS Canto system, using different fluorochrome-labeled monoclonal antibodies to EpCam, CD45, CD44, CD24, and N-cadherin. Five-year metastasis-free survival was evaluated by the Kaplan-Meier method. The differences were considered significant at p<0.05. Results. The results obtained demonstrated that the presence of both stem-like and non-stem CTCs showing signs of EMT with Epcam+CD45-CD44-CD24-Ncadherin+, Epcam+CD45-CD44+CD24-Ncadherin+, and Epcam(m)-CD45-CD44+CD24-Ncadherin+ phenotypes in the blood of breast cancer patients before treatment reduced the five-year metastasis-free survival rate (p=0.0016, p=0.017 and p=0.011, respectively). Conclusion. Thus, CTCs in the EMT state are informative for liquid biopsy to assess the risk of hematogenous metastasis and can be considered as targets for selection of personalized chemotherapy.