MELATONIN AND METFORMIN IN NEOADJUVANT HORMONOTHERAPY IN LOCALLY ADVANCED BREAST CANCER

Materials and methods. The effect of melatonin (MLT) and metformin (MTF) on the efficacy of neoadjuvant hormone therapy with toremifene was investigated in 54 patients with estrogen receptor-positive, locally advanced breast cancer (ER + BC). The average age of women was 67 years. The patients had no diabetes mellitus. The first group of patients (n = 19) received toremifene 120 mg per day, the second group (n = 16) - toremifene in combination with MLT 3 mg orally every night, the third group (n = 19) - toremifene in combination with MTF 850 mg twice daily. Randomization was performed - 1: 1: 1. The duration of therapy in all study groups was 4 months. After the end of treatment, all patients were undergone surgery. Further adjuvant treatment depended on the results of the postoperative pathomorphological conclusion. The primary endpoint was a decrease in the Ki-67% level (a surrogate marker for the effectiveness of hormone therapy), the secondary endpoints were the objective response, a pathological response in the tumor and lymph nodes, and the quality of life. Results. In all patients (n = 54), the frequency of decrease Ki-67 level and the frequency of objective response were 57% and 50%, respectively. At the same time, the incidence of Ki-67% level decrease in the «toremifene» group was 42%, in the «toremifene+MLT» group - 56%, in the «toremifene+MTF» group - 74%. Multifactor analysis showed that the addition of MTF to toremifene increases the chances of reducing Ki-67 compared with control 4.2 times (RR 4.23 [95% CI 1,04417,139], p = 0.043). It is important that only in the patients of the «toremifene+MTF» group a significant correlation was found between the Ki-67 index decrease in the tumor and the BMI value above the norm (p = 0.015). A complete pathomorphological response in the tumor and lymph nodes was not achieved in any patient. The objective response in the study groups was 31.6%, 86.7% and 47.3%, respectively. The addition of MLT to hormone therapy with toremifene significantly increased the frequency of the objective response from 31.6% to 86.7% (x2 = 10.32, p = 0.001). The inclusion into neoadjuvant hormone therapy with toremifene of MLT or MTF did not reduce the quality of life of patients, while in 50% of patients in the «toremifene+MLT» group there was an improvement in sleep.