RISK SCORE MODEL FOR PREDICTING CARDIOTOXICITY IN BREAST CANCER: DIAGNOSTIC VALUE OF HIGH-SENSITIVITY CARDIAC TROPONIN T. / ШКАЛА РИЗИКУ КАРДІОТОКСИЧНОСТІ У ХВОРИХ НА РАК ГРУДНОЇ ЗАЛОЗИ: ДІАГНОСТИЧНЕ ЗНАЧЕННЯ ВИСОКОЧУТЛИВОГО СЕРЦЕВОГО ТРОПОНІНУ Т.

Cardiovascular diseases are the second leading cause of death among breast cancer (BC) patients. Prediction of cardiovascular toxicity (CT) is an important part of the successful treatment and survival of patients. OBJECTIVE: to develop a risk score model for cardiovascular toxicity (CT) predicting, based on cardiovascular risk factors (RFs), RFs associated with cancer therapy, and troponin levels. MATERIAL AND METHODS: The study included 76 BC patients with a prospective analysis of their clinical and treatment data, RFs, echocardiographic indicators before the start of treatment and after 6 months, and an increase in troponin level. Among all RFs, the most significant RFs of CT were: radiation therapy, treatment with anthracyclines, and cardiovascular diseases. Based on the obtained results, a combined CT risk score was developed and proposed.According to the sum of points, patients were divided into groups: group 1 - with a low risk of CT development, the sum of points < 5; group 2 - moderate risk, 6-7 points; group 3 - high risk, > 8 points. RESULTS: In a pilot prospective study, an analysis of the RFs of CT was provided, compared to echocardiography data and the degree of troponin increase in dynamic observation; the risk score model for the CT prediction was developed for BC patients stratification. According to the developed score, BC patients with a total of > 8 points are considered to have a high risk of CT complications. CONCLUSIONS: The use of the proposed risk model score with calculation of the RFs of CT along with high-sensitivity troponin increase during cancer treatment allows predicting the risk of CT developing at the early stages - before the onset of clinical manifestations. Accordingly, these BC patients have a high risk of CT, and the use of personalized cardiac monitoring together with cardioprotective therapy can prevent cardiovascular complications.

CARDIOTOXICITY IN BREAST CANCER PATIENTS: RELATIONSHIP OF HS-TROPONIN T CHANGES AND HEART FUNCTION IN CANCER TREATMENT. / KARDIOTOKSYChNIST' U KhVORYKh NA RAK GRUDNOÏ ZALOZY: VZAIeMOZVIaZOK ZMIN TROPONINU T TA FUNKTsIÏ SERTsIa NA FONI KOMPLEKSNOÏ PROTYPUKhLYNNOÏ TERAPIÏ.

Breast cancer patients (BC) have a high risk of cardiotoxicity (CT) due to a combination of cancer treatments.Cardiovascular (CV) complications lead to delay or withdrawal of BC therapy and worsen the survival. Therefore, it isimportant to detect CT at the early stages before the occurrence of cardiac dysfunction and heart failure (HF) signs. OBJECTIVE: to study the dynamic changes of high-sensitivity (hs) troponin (Tn) T (hs-TnT) level in BC patients during cancer treatment with the use of chemotherapy and radiation therapy (RT) to predict and prevent CV complications during individualized management. MATERIAL AND METHODS: 40 BC patients were included in the pilot study. The analysis of the dynamic changes of hs-TnT and ejection fraction (EF) of the left ventricle (LV) was performed before and within 6 months of cancer treatment. Based on the data analysis, a definition of a significant increase in hs-TnT was developed and proposed. Therise of hs-TnT was calculated by the difference (%) between its baseline level and in the 6 months of cancer treatment. BC patients are grouped into tertiles according to the hs-TnT increase: group 1 - low level (0-50 %), group 2 -moderate level (> 50-100 %), and group 3 - high level (> 100 %). RESULTS: Before the start of cancer treatment, LVEF did not differ significantly between groups (mean EF (62.6 ± 1.0) %)and the hs-TnT level was also within normal values (0.008±0.001 ng/ml). In 6 months of cancer treatment, LVEF waswithin the normal ranges and did not differ significantly in patients of group 1. However, in patients of groups 2and 3 - LVEF drop (δLV EF) was 5.7 % (р < 0.01) and 10.8 % (р < 0.01), consequently. According to the correlationanalysis, the percentage of increase in hs-TnT (δhs-TnT) was associated with δEF LV (r = 0.39, р < 0.05) and the useof anthracyclines (AC) (r = 0.37, р < 0.05). Using logistic regression and ROC analysis, the diagnostic threshold valueof the hs-TnT increase > 165 % was defined, which can be considered as a reliable marker of early biochemical CT,with a sensitivity of 99 % and a specificity of 56 %. CONCLUSIONS: In BC patients, based on the level of hs-TnT increase, proposed a new early biochemical CT detectionmethod. Under the new approach, BC patients with hsTnT increase of > 165 % from baseline can be considered as areliable marker of early biochemical CT, with a sensitivity of 99 % and a specificity of 56 %.

PROGNOSTIC ROLE OF RESIDUAL TUMOR FEATURES IN HER2-NEGATIVE BREAST CANCER.

The aim of the study was to examine the prognostic value of immunobiological markers (tumor-infiltrating lymphocytes (TILs) and their subpopulations) in residual tumor after neoadjuvant chemotherapy (NACT) completion in patients with triple negative (TNBC) and luminal B HER2-neu negative breast cancer (LBBC). MATERIALS AND METHODS: The analysis of the treatment results of 59 patients with TNBC and 56 patients with LBBC with stage IIB-IIIB who received NACT was performed. The levels of TILs and their subpopulations (FOXP3+, CD4+, CD8+) in patients at the time of diagnosis in core-needle biopsy material and in residual tumor in postoperative material were studied by immunohistochemical method. RESULTS: The risk of recurrence in patients with LBBC who received NACT before surgery is associated mainly with 4 factors: FOXP3+ lymphocytes, Ki-67 index in residual tumor, the number of affected axillary lymph nodes after NACT and viable residual tumor volume. Analysis of the treatment outcome in patients with TNBC revealed that the lack of pathologic complete response (pCR) after NACT increases the risk of disease recurrence by 2.9 times, hazard ratio (HR) = 2.9 (95% confidence interval (CI) 1.4-6.1; p = 0.005) compared with patients in which pCR was achieved after NACT. It was also found that the presence of residual tumor in patients with TNBC after NACT increases the risk of death from this disease by 2.7 times (95% CI 1.0-7.1; p = 0.05). Increased intratumoral and stromal CD8+ lymphocyte counts in the residual tumor after NACT significantly reduces the risk of death from TNBC, HR = 0.6 (95% CI 0.5-0.9; p = 0.01) and HR = 0.6 (95% CI 0.4-0.9; p = 0.008), respectively. Increase in intratumoral CD4+ lymphocytes in residual tumor in the non-pCR group reduces by half the risk of death from TNBC, HR = 0.5 (95% CI 0.3-1.0; p = 0.05). CONCLUSION: The results of our study indicate a favorable prognostic value of TILS in residual tumor in TNBC. It is also reasonable to include the determination of the level of FOXP3+ lymphocytes in the residual tumor in the standard algorithms for stratification of risk groups.

CARDIOTOXICITY RISK PREDICTION IN BREAST CANCER PATIENTS. / PROGNOZUVANNIa RYZYKU KARDIOTOKSYChNOSTI U KhVORYKh NA RAK GRUDNOÏ ZALOZY.

Breast cancer patients receive combined antitumor treatment (surgery, chemotherapy, targeted drugs and radia-tion), so they are considered to be the patients with potentially high risk of cardiotoxicity (CT). Risk stratificationof cardiovascular complications before the beginning and during the cancer treatment is an important issue. OBJECTIVE: to develop a CT risk model score taking into account cardiological, oncological and individual risks. MATERIAL AND METHODS: The study included 52 breast cancer patients with retrospective analysis of their medicalhistory, risk factors, and echocardiographic parameters before the onset and in 12 months follow up. Based on theanalysis of the data, a CT risk model score was developed and recommended. The patients were divided into groupsaccording to the score: Group 1 - low risk of CT development - score < 4 points, Group 2 - moderate risk - 5-7points, Group 3 - high risk > 8 points. According to the scale, BC patients with a total of > 8 points are consideredto be at high risk for CT complications. Radiation therapy and anthracyclines, as well as associated cardiovasculardiseases were the most important risk factors of CT. RESULTS: Based on the study of retrospective analysis of risk factors, data of heart function monitoring during follow-up,the risk model score of cardiotoxicity has been developed for the BC patients' stratification. According to the proposedscore risk model, BC patients with a total score of > 8 points considered to have high risk of cardiotoxic complications. CONCLUSIONS: Using of the proposed risk model score with calculation of CT risk factors both before the beginningand during cancer therapy is important, because it allows predicting the risk of CT development - to identify high-risk patients, accordingly, to develop an individualized plan for cardiac function monitoring and to start timely cardioprotective therapy.

Prognostic role of androgen receptor expression in patients with metastatic triple negative breast cancer.

At present, there are no valid prognostic biomarkers in patients with triple negative breast cancer (TNBC) except well known clinical factors such as tumor size, lymph node status, differentiation grade and proliferation rate. AIM: To evaluate the prognostic role of androgen receptor (AR) expression in patients with TNBC. MATERIALS AND METHODS: The effect of the AR expression level in tumor tissue on overall survival depending on clinical, histological and immunohistochemical characteristics of the tumor was evaluated in 116 patients with metastatic TNBC. RESULTS: The independent prognostic value of AR expression in patients with TNBC of different stages was shown. The median overall survival was higher in patients with AR-positive tumors compared with AR-negative tumors (57 months vs 27 months, p < 0.0001). Five-year survival since diagnosis in the group with AR-positive TNBC was 47.6 ± 8.3% vs 20.0 ± 5.3% in the group with AR-negative TNBC (p < 0.05). CONCLUSIONS: The results of our study indicate a favorable impact of AR expression on the overall survival of TNBC patients.

[THE TOXIC EFFECTS OF CHEMOTHERAPY ON THE GASTROINTESTINAL TRACT].

Chemotherapy in modern oncology is one of the main methods of treatment, along with surgery and radiotherapy techniques. More than 60% of patients receiving chemotherapy at different stages of treatment. Recently, modern chemotherapy has become more urgent personal approach to the choice of drugs and their doses, aimed at reducing the toxicity of chemotherapy. Complications of chemotherapy significantly degrade the effectiveness of the treatment of patients with malignant tumors, because they require lower doses of anticancer drug, or lengthening the intervals between cycles of chemotherapy, which affects treatment outcomes and quality of life.

[MODERN APPROACHES TO THE DIAGNOSIS AND TREATMENT OF CHEMOTHERAPY TOXICITY IN PATIENTS WITH BREAST CANCER].

The use of modern chemotherapy (CT) allowed to achieve significant progress in the treatment of many malignant tumors that were previously considered fatal. Improving the efficiency of the treatment was achieved by the intensification of chemotherapy. However, intensification of chemotherapy regimes provoked increase in the number of side effects of anticancer therapy,which often lead to a decrease in the intensity of the selected mode, the additional financial costs of treating the complications and the formation of the negative attitude of the patient to treatment. Thus, the side effects of chemotherapy are the actual problem of modern oncology. The purpose of this literature review was to investigate the frequency, symptoms and ways to prevent and treat various types of toxicity of chemotherapy.