METFORMIN AND DUCTAL CARCINOMA IN SITU OF THE BREAST: MOLECULAR MECHANISMS, EVIDENCE, AND CLINICAL PERSPECTIVES

Abstract

Introduction: Breast cancer is the most common neoplasm among women worldwide, with ductal carcinoma in situ (DCIS) being an early and non-invasive form that accounts for about 20% of diagnoses. Metformin, widely used in the treatment of type 2 diabetes, has attracted interest due to its potential antitumor effects. Objectives: To compile information on the antitumor mechanisms of action of metformin, its direct and indirect mechanisms in breast ductal carcinoma in situ, and to discuss clinical perspectives. Methodology: This study conducted a narrative literature review covering publications from 2010 to 2025, aiming to investigate the molecular mechanisms, experimental evidence, and clinical perspectives of metformin use in DCIS. Results: Thirteen articles addressing the direct and indirect effects of metformin on tumor cells were analyzed. The direct mechanisms involve the activation of AMPK, which inhibits the mTOR pathway, reducing cell proliferation and inducing apoptosis. Indirectly, metformin decreases serum insulin and glucose levels, limiting energy availability for neoplastic cells. Preclinical studies show promising results in reducing tumor growth and increasing sensitivity to conventional therapies, while clinical trials still present heterogeneous results and are not specific to DCIS. Conclusions: It is concluded that metformin is a low-cost and easily accessible agent with adjuvant therapeutic potential for the treatment of DCIS, although further research with specific samples is needed to assess its efficacy and safety in Treatment.