Phenotypic Characterization of Molecular Biological Variants of Individual Her2-positive Circulating Tumor Cells in Luminal Molecular Subtypes of Breast Cancer

Aim. To study the co-expression patterns of molecular biological subtype (MBS) markers on individual circulating tumor cells (CTCs) in luminal subtypes of breast cancer (BC) and their association with the expression of stemness and epithelial – mesenchymal transition (EMT) markers.

Materials and methods. The study analyzed venous blood and primary tumor biopsies from 51 BC patients (N1– 4N0–3M0), including 21 cases with luminal A, 19 cases with luminal B (HER2–), and 11 cases with luminal B (HER2+) MBS. Flow cytometry was used to assess the expression of CD45, EpCAM, N-/E-cadherin, CD44, CD24, CD133, Her2neu, ER, PR, and Ki67 in CTCs before therapy initiation. Statistical analysis was performed using Statistica 10.0 (p < 0.05).

Results. In luminal A and B (HER2–) primary tumor MBS, phenotypic conversion of CTCs was observed, characterized by the emergence of HER2+ CTCs, which were often ER-negative and exhibited various coexpression patterns of stemness markers. The key practical finding was the identification of a metastasis-associated CTC phenotype in luminal HER2– MBS: CD45–EpCAM+ER–PR–Her2neu+Ki67–. This phenotype corresponds to the classical HER2+ subtype at the level of a single cell.

Conclusion. The study results support the feasibility of determining MBS marker expression on a single CTC for predicting the risk of hematogenous metastasis in luminal A and B (HER2–) primary tumor MBS and for optimizing treatment strategies.

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