The effect of carcinoembryonic antigen on cytokine production in breast cancer patients

Introduction. Despite the fact that several studies have found a correlation between the level of carcinoembryonic antigen (CEA) in the blood and the molecular subtypes of breast cancer (BC), there are limitations to using CEA as a cancer marker in the early stages of BC due to its lack of sensitivity. New approaches are needed to improve the methodology for using CEA in detecting BC.

Aim. To evaluate the effect of CEA on the production of cytokines by blood leukocytes in patients with BC with various molecular subtypes.

Materials and methods. Blood samples of 109 women with breast cancer aged 25–85 years were analyzed. Patients with breast cancer were divided into five subgroups according to the molecular subtype. Enzyme immunoassay was used to study spontaneous and CEA-induced cytokine production: IL-6, IL-8, IL-10, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF and MCP-1. Results. In the luminal A subtype, there was a decrease in spontaneous and CEA-induced cytokine production compared to other molecular subtypes of breast cancer. When analyzing the ROC curves, it was found that exceeding the threshold values of the CEA influence index (II_CEA) on the production of TNF-α and G-CSF is characteristic of the luminal B HER2-negative subtype.
In the luminal B HER2 positive subtype, the following thresholds were exceeded: CEA of induced IL-6, IL-8, TNF-α and MCP-1 products; as well as II_CEA for IL-1Ra products. The HER2 positive subtype corresponded to exceeding the thresholds: spontaneous production of IL-8, G-CSF and MCP-1; CEA and II_CEA for GM-CSF products. The triple negative subtype was characterized by an increase in II_CEA thresholds for IL-8 products.

Conclusion. The determination of CEA-induced cytokine production by blood cells in patients with breast cancer makes it possible to identify molecular subtypes with an unfavorable outcome, in particular triple negative and HER2 positive subtypes even before surgery.

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