ASPO Abstracts
Effects of metformin on breast density and anthropometric measures in a Phase II clinical trial in premenopausal women with components of metabolic syndrome
Category: Lifestyles Behavior, Energy Balance & Chemoprevention
Conference Year: 2022
Abstract Body:
Background: Breast density and obesity are risk factors for breast cancer development. Women with high breast density have a 4-6 fold increased risk of breast cancer development compared to women with low breast density. Tumors that arise from dense breasts also have a worse prognosis. Moreover, obesity increases post-menopausal breast cancer risk and may increase the risk for triple-negative breast cancer in premenopausal women. There is a need for intervention strategies aiming to reduce breast density and obesity-associated dysregulation to attenuate 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, assessment of compliance to the study agent, and differences by ethnicity. Results: We analyzed breast density measurements at the baseline visit by ethnicity and identified a significant difference in the dense volume, with Hispanics having a lower dense volume compared to Non-Hispanics (p= 0.044). No differences were found in the non-dense volume or percent density after evaluating differences by ethnicity. After the intervention, metformin treatment led to a significant reduction in waist circumference (p<0.001) and waist-to-hip ratio (p=0.019) compared to the placebo arm. 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). Conclusions: We conclude that metformin intervention resulted in favorable changes in anthropometric measures of adiposity including waist circumference, waist-to-hip ratio, and a significant decrease in non-dense breast volume in women within the metformin group. Future studies will examine transcriptional changes in pathways associated with breast cancer risk in breast tissue collected throughout the study.
Keywords: Breast Cancer Risk, Metformin, Breast Density, Clinical Trial, Chemoprevention