Metformin, promising adjuvant therapy for breast cancer treatment in obese postmenopausal women

Metformin is the first-line treatment for patients with type 2 diabetes and could be used in PCOS (polycystic ovarian syndrome) management. Some studies have reported that patients with various cancers may therapeutically benefit from metformin. Metformin's anti-tumour activity could be linked to its negative impact on metabolism.

In this context, Aya Ahmed El-attar from Tanta University in Tanta, Egypt, and colleagues aimed to evaluate the effect of metformin as an adjuvant therapy to letrozole on estradiol and other biomarkers involved in the breast cancer pathogenesis of breast cancer among overweight and obese postmenopausal women in an open-labelled parallel pilot study.

For this purpose, the researchers assessed seventy-five female postmenopausal stages II–III breast cancer patients for eligibility. Forty-five patients met the inclusion criteria and were categorized into three arms: the lean arm comprising 15 women who received letrozole 2.5 mg/day; the metformin arm comprising 15 overweight/obese women who received letrozole 2.5 mg/day plus metformin (2000 ± 500 mg/day), and control arm comprising 15 overweight/obese women who received letrozole 2.5 mg/day. The duration of the intervention was six months. Blood samples were analyzed at baseline and six months after the intervention to measure serum estradiol, osteocalcin, leptin levels, serum insulin, and fasting blood glucose concentration.

The authors reported the following findings:

• After the intervention and compared to the control arm, the metformin arm showed a significantly lower ratio to the baseline (significant reduction) for estradiol, leptin, fasting blood glucose, insulin, osteocalcin serum levels, and the homeostatic model assessment of insulin resistance "HOMA-IR" value.
• There was a non-significant variation in the lactate ratio to the baseline among the three study arms.

Metformin exerts anti-cancer activity by reducing the high levels of circulating estrogen linked to the pathogenesis of postmenopausal breast cancer. Metformin is an insulin sensitizer that decreases glucose and insulin levels. Metformin alleviates the high insulin level correlated with the proliferation of cancer cells and poor clinical outcomes. Also, metformin negatively affects leptin which promotes estrogen biosynthesis.

"The findings obtained from the study prove the possible tolerability and safety of metformin and advocate that it could be a promising adjuvant therapy to letrozole in obese/overweight postmenopausal women with breast cancer secondary to its favorable effects on estradiol and other biomarker involved in breast cancer pathogenesis," the researchers wrote." However, still, there is a need for large-scale and more longitudinal studies."

Reference:

El-attar, A.A., Ibrahim, O.M., Alhassanin, S.A. et al. 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. Eur J Clin Pharmacol (2022). https://doi.org/10.1007/s00228-022-03444-6