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.
Reconstruction options for locally advanced breast cancer cases and their impact on the quality of life