الفهرس 
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Abstract
This study aimed to evaluate the implication of a combination of metformin adjuvant therapy and aromatase inhibitor ( letrozole) in postmenopausal overweight/obese women with breast cancer. In addition, we aimed to evaluate the effect of weight reduction on aromatase inhibitor efficacy. Seventy-five postmenopausal stage 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 six months. Blood samples were obtained at baseline and six months after intervention for the measurement of serum estradiol, leptin, osteocalcin levels, fasting blood glucose concentration, and serum insulin. After the intervention and as compared to the control arm, the metformin arm showed a significant reduction in estradiol, leptin, fasting blood glucose, insulin, osteocalcin serum levels, and the homeostatic model assessment of insulin resistance ”HOMA-IR” index. Metformin was well tolerated and exhibited mild and transient side effects. We conclude that metformin may exert anti-cancer activity through 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. However, we recommend large-scale and more detailed studies to confirm the promising results obtained with the current study.