Melatonin and metformin in neoadjuvant chemotherapy in locally advanced breast cancer

Abstract

Background: According to in vitro/in vivo studies both melatonin (MLT) and metformin (MTF) may exhibit an antitumor effect. Furthermore, in accordance to epidemiological studies MTF reduces the risk of developing breast cancer (BC) among patients with diabetes mellitus; as well as “light at night”can inhibit endogenic MLT synthesis and increase risk of breast cancer. Thus, MLT and MTF need to be investigated in clinical oncology. Methods: A total of 53 patients with locally advanced BC (ER positive/HER2 negative ‐68%, ER positive/HER2 positive ‐25% and ER negative/HER2 negative ‐7%), were included in the study of MLT or MTF efficiency in combination with anthracyclin and taxan‐containing neoadjuvant chemotherapy (NACT) (clinicalTrials.gov NCT02506777). The average patients’ age was 56 years. All patients had no history of diabetes mellitus. All patients were randomized into 3 groups. The first group (n = 20) received NACT, the second one (n = 21) received NACT in combination with 3 mg overnight dose of oral MLT, the third group (n = 12) received NACT in combination with oral MTF (850 mg twice a day). For all patient groups the NACT duration was 6 cycles, then surgery was performed. Results: An objective response rate for three studied groups was 85%, 85.7% and 75% respectively. According to multivariate analysis of results the NACT combination with MLT and MTF does not lead to increase of pathomorphological response (pCR) rate compared to NACT group (OR 0.482 [95% CI 0,083‐2,792], p=0.416; OR 0.602 [95% CI 0,085‐4,284], p=0.612). pCR rate was in 25%, 14,2% и 16,6% accordingly. The quality of life was assessed by EORTC‐QLQ‐C30. In the group of patients who received NACT+MLT, in contrast to the group of patients who received only NACT, the values on the role functioning (RF), fatigue (FA) and sleep (SL) scales did not decrease during the treatment (p = 0.008, p = 0.004, p = 0.014 respectively). Conclusions: MLT and MTF did not show influence on pCR and objective response rates, however, MLT used during NACT may improve the quality of life. Legal entity responsible for the study: T. Semiglazova. Funding: Federal State Budget Institution “National Medical Research Center of Oncology na N.N. Petrov” Ministry of Healthcare of Russian Federation. Disclosure: All authors have declared no conflicts of interest.