The impact of metformin use on the outcomes of locally advanced breast cancer patients receiving neoadjuvant chemotherapy: an open-labelled randomized controlled trial.

Recently, several clinical trials have attempted to find evidence that supports the anticancer use of metformin in breast cancer (BC) patients. The current study evaluates the anticancer activity of metformin in addition to neoadjuvant chemotherapy (NACT) in locally advanced BC patients. Additionally, we assess the safety and tolerability of this combination and its effect on the quality of life (QoL) of BC patients. Eighty non-diabetic female patients with proven locally advanced BC were randomized into two arms. The first arm received anthracycline/taxane-based NACT plus metformin. The second arm received anthracycline/taxane-based NACT only. Overall response rate (ORR), clinical complete response (cCr), pathological complete response (pCR), and breast conservative rate (BCR) were evaluated between both groups, and correlated with serum metformin concentration. ORR, cCr, pCR, and BCR increased non-significantly in the metformin group compared to the control group; 80.6% vs 68.4%, 27.8% vs 10.5%, 22.2% vs 10.5%, and 19.4% vs 13.2%, respectively. A trend towards cCR and pCR was associated with higher serum metformin concentrations. Metformin decreased the incidence of peripheral neuropathy, bone pain, and arthralgia, although worsened the gastrointestinal adverse events. Metformin combination with NACT has no effect on the QoL of BC patients. Metformin combination with NACT is safe, tolerable, and improves non-significantly the clinical and pathological tumor response of BC patients.