A randomized controlled trial of metformin in women with components of metabolic syndrome: intervention feasibility and effects on adiposity and breast density
Edgar Tapia, Diana Evelyn Villa-Guillen, Pavani Chalasani, Sara Centuori, Denise J Roe, Jose Guillen-Rodriguez, Chuan Huang, Jean-Phillippe Galons, Cynthia A Thomson, Maria Altbach, Jesse Trujillo, Liane Pinto, Jessica A Martinez, Amit M Algotar, H-H Sherry Chow, Edgar Tapia, Diana Evelyn Villa-Guillen, Pavani Chalasani, Sara Centuori, Denise J Roe, Jose Guillen-Rodriguez, Chuan Huang, Jean-Phillippe Galons, Cynthia A Thomson, Maria Altbach, Jesse Trujillo, Liane Pinto, Jessica A Martinez, Amit M Algotar, H-H Sherry Chow
Abstract
Purpose: 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.
Methods: 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 = 76) or placebo (n = 75) 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.
Results: Seventy-six percent in the metformin arm and 83% in the placebo arm (p = 0.182) completed the 12-month intervention. Adherence to study agent was high with more than 80% of participants taking ≥ 80% 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 < 0.001) and waist-to-hip ratio (p = 0.019). 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 = 0.070).
Conclusion: 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.
Trial registration: ClinicalTrials.gov NCT02028221. Registered January 7, 2014, https://ichgcp.net/clinical-trials-registry/NCT02028221.
Keywords: Anthropometric measures; Breast density; Clinical trial; Metabolic syndrome; Metformin.
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Source: PubMed