Tehran University Medical Journal

Background: Metformin has been suggested as anti-cancer in retrospective studies. We design a prospective controlled study about metformin efficacy in the window time between biopsy and definite surgery with changes of Ki-67 as the primary endpoint.

Methods: The primary cohort had composed of 50 pathologically diagnosed invasive breast cancers, accrued in Medical Oncology Department of Iran Cancer Institute from February to November 2014. Patients neither had indication of neoadjuvant chemotherapy, nor involved with diabetes mellitus. They followed during the time period of biopsy and definitive surgery with taking tests on pathology specimens for ER, PgR, HER-2/neu and Ki-67 index. We checked fasting insulin and glucose level as well as quality of life and adverse effects in both times in the intervention group. Metformin (1500 mg/day) was prescribed to intervention group from pathology report to the night before surgery.

Results: From 45 patients, 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 Ki-67 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. Patients tolerated metformin very well, but mild gastrointestinal symptoms were seen in 30% of cases. There was a correlation between metabolic factor of HOMA score (fasting insulin level fasting blood sugar/405) and changes in Ki-67.

Conclusion: 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. To find direct apoptotic stimulation of metformin and long-term results of this drug further studies in the adjuvant settings with cooperation of pharmacokinetic groups are recommended.