Harashchenko O. Optimization of the diagnostic and treatment algorithm in breast cancer patients

The dissertation presents for the first time a scientific justification and a new solution to a problem that is relevant for modern oncology - increasing the effectiveness of the treatment of patients with breast cancer by developing a diagnostic and treatment algorithm, which includes studying the possibilities of personalizing diagnosis, treatment and monitoring the clinical course of the disease using PCT schemes after determining individual sensitivity of tumor cells to cytostatic action and creation of a diagnostic miRNA panel. The use of an optimized diagnostic and treatment algorithm in patients who were treated taking into account the sensitivity of the tumor to PCT in the neoadjuvant regimen compared to patients who underwent PCT according to standard protocols, led to a significant increase in the treatment effectiveness of patients with breast cancer. The overall 3-year survival rates in the study and control groups were 92.06+3.8% and 82.3+5.0%, respectively, while the 5-year survival rates were 88.2+5.0% and 80.4+ 10.5% respectively. The difference of these indicators is statistically significant (p = 0.04). The 3-year recurrence-free survival rates in the study and control groups were 72.4+6.7% and 76.5+8.4%, respectively, and the 5-year survival rates were 58.6+9.0% and 31.7+9 .5% respectively. The difference is statistically significant only for indicators of 5-year recurrence-free survival (26.9%, p = 0.03). Thanks to the analysis of the level of plasma miRNAs of the patients, trends in their correlation with the clinical course of the disease were determined, which can be a reasonable starting point for the development of an individual therapy strategy. When evaluating the levels of miRNA expression, it was found that the age characteristics of the patients were significant in terms of changes in the expression of miRNA-27 and miRNA-497 equally for the group that received APHT and after NPHT. At the same time, the expression of these 2 miRNAs had the opposite dependence, in miRNA-27 it was significantly lower in premenopausal women and increased with age, and the expression of miRNA-497 was significantly higher in patients regardless of age. In the course of clinical monitoring of female patients, it was established for the first time that, compared to healthy women, the expression of miRNA in breast cancer patients has certain differences. Namely, there is a trend towards an increase in the expression of miRNA-497 at IIIA-IV stage and miRNA-200 at IV stage, as well as a decrease of miRNA-27 at IIV-IV stage. The conducted study opens up the prospects of using data from the analysis of the expression of the specified miRNAs for the purpose of evaluating the effectiveness of treatment and forecasting the clinical course of the disease in patients with breast cancer.