TY - JOUR
T1 - A randomized controlled trial of metformin in women with components of metabolic syndrome
T2 - intervention feasibility and effects on adiposity and breast density
AU - Tapia, Edgar
AU - Villa-Guillen, Diana Evelyn
AU - Chalasani, Pavani
AU - Centuori, Sara
AU - Roe, Denise J.
AU - Guillen-Rodriguez, Jose
AU - Huang, Chuan
AU - Galons, Jean Phillippe
AU - Thomson, Cynthia A.
AU - Altbach, Maria
AU - Trujillo, Jesse
AU - Pinto, Liane
AU - Martinez, Jessica A.
AU - Algotar, Amit M.
AU - Chow, H. H.Sherry
N1 - Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/11
Y1 - 2021/11
N2 - 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://clinicaltrials.gov/ct2/show/NCT02028221
AB - 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://clinicaltrials.gov/ct2/show/NCT02028221
KW - Anthropometric measures
KW - Breast density
KW - Clinical trial
KW - Metabolic syndrome
KW - Metformin
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U2 - 10.1007/s10549-021-06355-9
DO - 10.1007/s10549-021-06355-9
M3 - Article
C2 - 34383179
SN - 0167-6806
VL - 190
SP - 69
EP - 78
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -