Abstract 195P
Background
Molecular subtype of breast cancer is a criterion that determines the treatment tactic and the prognosis of the clinical course of the disease. At the same time, CTCs can arise from the minor subpopulation of primary tumor cells, that do not express target molecules for prescribed therapy. Here we assessed the presence of ER/PR/Her2+ and Ki-67 in subpopulations of CTCs with different manifestations of EMT and stemness, which could dramatically effect on their capacity to migration, proliferation and finally forming a clinically detectable macrometastsis.
Methods
The prospective study included 84 breast cancer patients with stage T2-4N0-3M0. CTCs were detected only in 45 out 84 cases (54%). 256 phenotypes of CTCs were detected by flow cytometry (Novocyte 3000, ACEA Biosciences, USA) using monoclonal antibody cocktail.
Results
Patients were represented in a two-dimensional tSNE plane, and two clusters were identified via principal component analysis (PCA). In patients belonging to cluster 2 the number of CTCs was 3 times higher (p=0,00002). Cluster 1 included patients with three molecular subtypes (luminal A, luminal B, triple-negative (TN)), while cluster 2 was represented only by luminal subtypes. There were more patients with luminal A subtype in cluster 2 (p=0,06). Only 6 CTCs phenotypes were significantly different in two clusters. All phenotypes were characterized by absence of EMT traits and did not have the ability to proliferate. It is noteworthy that in cluster 2 the TN phenotypes of CTCs were predominant, while there were no patients with TN molecular subtype this cluster. A comparative analysis of the two clusters, depending on the clinicopathological parameters, revealed significant differences between patients having menstrual cycle and menopausal patients in cluster 2. Menopausal patients had more CTCs corresponding to TN phenotype, with no features of stemness, EMT and proliferation. Subpopulation of CTCs corresponding to luminal A subtype, with CD133 expression, without traits of EMT and proliferation, on the contrary, were less in menopausal patients.
Conclusions
The presence of CTCs corresponding to TN subtype in the cluster 2 confirms the possibility of tumor cells to converse molecular subtype during extravasation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Russian Science Foundation (grant #19-75-30016).
Disclosure
All authors have declared no conflicts of interest.