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Abstract
Introduction. The detection of circulating tumor cells (CTCs) is associated with a poor prognosis in patients with metastatic breast cancer (BC). However, there is insufficient data to prove the prognostic value of CTC detection, their threshold level and phenotypic characteristics in patients with early-stage breast cancer (EBC).
Aim. To study the effect of CТC on the course of EBC, taking into account their level and qualitative composition using the flow cytometry method in accordance with the original methodology of the A. Tsyb MRRC.
Materials and Methods. The study involved 79 patients with EBC. The average age of the patients was 50 years. The median follow-up period was 43.3 months. Involvement of regional lymph nodes was found in half of the patients (53.2 %). The most common biological subtype of the tumor was triple negative (32.9 %). Before starting therapy, all patients underwent a CTC assessment using multiparameter flow cytometry according to the original methodology of the A. Tsyb MRRC. The number of CTCs and their immunophenotypic features were evaluated based on an analysis of the expression of CAM5.2, BerEP4, HLA-DR, and CD95 antigens. All patients were treated according to the stage and biological subtype of the tumor in accordance with the clinical recommendations of the Ministry of Health of the Russian Federation.
Results. CTCs in peripheral blood were detected in 43 patients (54.4 %), their number ranged from 2 to 98 cells in 7.5ml of blood. We have established that the threshold value that significantly affects the prognosis for EBC is 5 CTC in 7.5 ml of blood. The 3-year overall survival (OS) rate was 63.2% in the group with ≥5 CTC (n = 19), compared to 95% in the group with <5 CTC (n = 60), (p < 0.001). Similarly, the 3-year progression-free survival (PFS) rate was 47.4% and 90%, respectively (p < 0.001). Research has established the particular characteristics of the qualitative composition of CTC in relation to prognosis. The group with the CTC immunophenotype CAM5.2+BerEP4+ was prognostically unfavorable compared with the CAM5.2+BEREP4 group- 3-year OS, 80% vs. 100% (p = 0.008); 3-year FPS, 72.3% vs. 100%, respectively, (p = 0.012).
Conclusion. CTCs in EBC are detected in 54.4 % of cases and represent an immunophenotypically heterogeneous subpopulation of tumor cells with respect to the expression of pan-epithelial markers, which are significantly associated with the prognosis of EBC.
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