A randomized controlled trial of metformin in women with components of metabolic syndrome: intervention feasibility and effects on adiposity and breast density

Abstract

Obesity is a known risk factor for post-menopausal breast cancer and may increase risk for triple negative breast cancer in premenopausal women. Intervention strategies are clearly needed to reduce obesity-associated breast cancer risk. We conducted a Phase II double-blind, randomized, placebo-controlled trial of metformin in overweight/obese premenopausal women with components of metabolic syndrome to assess the potential of metformin for primary breast cancer prevention. Eligible participants were randomized to receive metformin (850 mg BID, n\u2009=\u200976) or placebo (n\u2009=\u200975) for 12 months. Outcomes included breast density, assessed by fat/water MRI with change in percent breast density as the primary endpoint, anthropometric measures, and intervention feasibility. Seventy-six percent in the metformin arm and 83% in the placebo arm (p\u2009=\u20090.182) completed the 12-month intervention. Adherence to study agent was high with more than 80% of participants taking\u2009≥\u200980% assigned pills. The most common adverse events reported in the metformin arm were gastrointestinal in nature and subsided over time. Compared to placebo, metformin intervention led to a significant reduction in waist circumference (p\u2009<\u20090.001) and waist-to-hip ratio (p\u2009=\u20090.019). Compared to placebo, metformin did not change percent breast density and dense breast volume but led to a numerical but not significant decrease in non-dense breast volume (p\u2009=\u20090.070). We conclude that metformin intervention resulted in favorable changes in anthropometric measures of adiposity and a borderline decrease in non-dense breast volume in women with metabolic dysregulation. More research is needed to understand the impact of metformin on breast cancer risk reduction. ClinicalTrials.gov NCT02028221. Registered January 7, 2014, https://clinicaltrials.gov/ct2/show/NCT02028221