Metformin anti-proliferative effect on a cohort of non-diabetic breast cancer patients

Abstract

Background: Whereas the preoperative period is increasingly popular for the clinical investigation of new biological agents and also establishment of Ki67 as an intermediate proliferative marker of treatment benefit, Methods: we design a prospective randomized controlled study about metformin efficacy in the window time between biopsy and definite surgery. Our primary endpoint was changes of Ki67. Patients neither had indication of neoadjuvant chemotherapy, nor involved with diabetes mellitus. They followed during the time period of biopsy and definitive surgery. Metformin (1500mg/day) was prescribed to intervention group from pathology report to the night before surgery. Control group were patients with the same inclusion criteria who did not receive any drug. Results: From 50 patients enrolled 5 excluded. Four before using any pills and one in the first day of taking metformin; 25 had been received metformin for median time of 2.8 weeks. Controlled group included 20 patients who followed in the window time. There were no statistically significant differences between two groups regarding baseline clinical and tumor characteristics such as age, stage, grade, Er, Pgr, HER2 status, time and type of surgery. However, immunohistochemistry study showed decrease of median KI67 from 35.14 to 29.6 in the intervention group and increase from 24.5 to 30.6 in the control group. Both of these results were statistically significant. Although mild gastrointestinal symptoms were seen in 30% of cases, generally patients tolerated metformin very well. There was a correlation between metabolic factor of HOMA score and changes in KI67. Conclusions: In the present study metformin prescription in the short period of time between biopsy and definite surgery had shown inhibition of breast cancer cell growth. We found relationship between metformin anti-proliferative effect and glucose and insulin metabolism.