Effect of metformin as an adjuvant therapy to letrozole on estradiol and other biomarkers involved in the pathogenesis of breast cancer in overweight and obese postmenopausal women: a pilot study

INTRODUCTION: Metformin may provide a therapeutic benefit in different types of malignancy. PURPOSE: We aimed at evaluating the effect of metformin as an adjuvant therapy to letrozole on estradiol and other biomarkers involved in the pathogenesis of breast cancer in overweight and obese postmenopausal women. METHODS: Seventy-five postmenopausal stages II–III breast cancer female patients were assessed for eligibility in an open-labeled parallel pilot study. Forty-five patients met the inclusion criteria and were assigned into three arms: the lean arm (n = 15) women who received letrozole 2.5 mg/day, the control arm (n = 15) overweight/obese women who received letrozole 2.5 mg/day, and the metformin arm (n = 15) overweight/obese women who received letrozole 2.5 mg/day plus metformin (2000 ± 500 mg/day). The intervention duration was 6 months. Blood samples were obtained at baseline and 6 months after intervention for the measurement of serum estradiol, leptin, osteocalcin levels, fasting blood glucose concentration, and serum insulin. RESULTS: After the intervention and as compared to the control arm, the metformin arm showed a significantly lower ratio to the baseline (significant reduction) for estradiol (p = 0.0433), leptin (p < 0.0001), fasting blood glucose (p = 0.0128), insulin (p = 0.0360), osteocalcin serum levels (p < 0.0001), and the homeostatic model assessment of insulin resistance “HOMA-IR” value (p = 0.0145). There was a non-significant variation in the lactate ratio to the baseline among the three study arms (p = 0.5298). CONCLUSION: Metformin may exert anti-cancer activity by decreasing the circulating estradiol, leptin, and insulin. Metformin might represent a safe and promising adjuvant therapy to letrozole in overweight/obese postmenopausal women with breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05053841/Registered September 23, 2021 - Retrospectively.