Evaluation of Metformin in Combination with Neoadjuvant Therapy in Breast Cancer Patients

Background: Metformin has demonstrated the potential to suppress cancer cell proliferation and growth via several mechanisms, primarily through activation of the AMP-activated protein kinase (AMPK) pathway. This activation reduces insulin levels and subsequently inhibits protein synthesis and the mammalian target of rapamycin (mTOR) signaling pathways. Objectives: This research aimed to assess the efficacy and safety of combining metformin with standard neoadjuvant chemotherapy (NACT), emphasizing its influence on pathological complete response (pCR), toxicity and progression-free survival (PFS). Patients and methods: A phase II prospective clinical trial was conducted on 60 non-diabetic female patients with histologically proven breast cancer (≥ 18 years, performance status ≤ 2, normal organ function, stage II–III, luminal A/B, triple-negative, or HER2-positive subtypes and baseline left ventricular ejection fraction (LVEF) > 50%). Participants were randomly divided into two groups: group I received standard Anthracycline- and Taxane-based NACT with or without anti-HER2 therapy combined with metformin, while group II received the same regimen without metformin. Results: Baseline clinical and pathological characteristics were comparable between both groups. The median age was 42.5 (20–61) in group I and 42 (27–73) years in group II. Ductal carcinoma was the predominant histological type in both groups (96.7% vs. 90%), with most cases presenting as stage III (65.7% vs. 63.3%) and grade II (86.7% vs. 80%). The metformin group showed significantly higher breast conservation rates and lower grades of diarrhea and oral mucositis (p = 0.038, 0.018 & 0.014 respectively). However, no significant differences were observed in pCR or PFS. Pathological response was significantly correlated with patients’ weight and BMI (p = 0.036 and 0.044 respectively). Conclusion: Metformin was well tolerated and associated with improved breast conservation rates and reduced mucosal toxicity.