Abstract P1-10-02: Effect of metformin on metabolic markers associated with breast cancer risk in a phase II clinical trial in overweight/obese premenopausal women
Authors: Tapia Edgar , Villa-Guilen Diana , Chalasani Pavani , Centuori Sara , Roe Denise J. , Guillen Jose , Cordova Catherine , Pinto Liane , Chow Sherry 
Published: March 2022

Abstract
Background: The increasing rate of obesity in the United States is accompanied by serious health concerns. Obesity increases breast cancer burden and is associated with increased risk of triple-negative breast cancer in premenopausal women and overall poor prognosis in breast cancer patients. There is a need for intervention strategies aiming to reduce obesity-associated dysregulation to attenuate breast cancer risk.Methods: We conducted a Phase II, double-blind, randomized, placebo-controlled clinical trial in overweight/obese premenopausal women with elements of metabolic syndrome to assess the potential of metformin to reduce obesity-associated breast cancer risk. Study participants received metformin (850 mg BID, n = 76) or placebo (n = 75) for 12 months. Fasting blood samples were collected at baseline, 6-months and 12-months from each participant. We analyzed the effects of metformin on circulating levels of insulin/IGF axis, adipokines, and neutrophil-to-lymphocyte ratio in samples collected from this trial. Serum concentrations of insulin, IGF-1, IGFBP-3, leptin and high-molecular weight adiponectin were measured using ELISA immunoassays. Results: The study population included 151 women and had a mean age of 39.5 years, mean body mass index (BMI) was 37.8 and study participants had a large waist and at least one other component of metabolic syndrome. Metformin treatment did not result in significant changes in members of the insulin/IGF axis compared to the placebo group, however, limiting the analysis to participants with detectable metformin in the blood serum resulted in favorable changes in insulin (p=0.0215), HOMA-IR (p&lt;0.001) and a significant increase in IGFBP-3 (p=0.0176) in the metformin group after the intervention. We observed significant decreases in leptin (p=0.0018) and the leptin-to-adiponectin ratio (p=0.0036) in the metformin arm longitudinally. Additionally, we observed a significant reduction in the neutrophil-to-lymphocyte ratio (NLR), a systemic inflammation marker, in the metformin group compared to the placebo group (p=0.0170). Conclusions: We conclude that metformin led to favorable changes in metabolic markers associated with breast cancer risk in the metformin treated participants, however, the changes were not significantly different from the placebo group. The NLR was significantly reduced after metformin intervention compared to the placebo group. More research is needed to understand the effects of metformin on the insulin/IGF axis and adipokines in overweight/obese premenopausal women.
Citation Format: Edgar Tapia, Diana Villa-Guilen, Pavani Chalasani, Sara Centuori, Denise J. Roe, Jose Guillen, Catherine Cordova, Liane Pinto, Sherry Chow. Effect of metformin on metabolic markers associated with breast cancer risk in a phase II clinical trial in overweight/obese premenopausal women [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-10-02.