Abstract A16: Molecular tracking of metformin chemoprevention in a 300-person ALLIANCE randomized placebo controlled trial in women at high risk for triple-negative breast cancer

Abstract

Abstract Background: Metformin (1,1-dimethylbiguanide hydrochloride) is a well-tolerated biguanide currently undergoing testing for secondary breast cancer prevention in women with prior breast cancer. Recently published population studies suggest that metformin decreases the incidence of cancer and cancer-related mortality in diabetic patients. While metformin is one of the most extensively studied drugs in vitro and in vivo, many pre-clinical studies use concentrations of metformin that are >1,000 times what is clinically achievable in humans and would be rapidly fatal if achieved. As a result, the molecular action of metformin in the breast tissue of women at high-risk who take metformin chemoprevention is poorly understood. Methods/Results: Here we use combined proteomic profiling, breast tissue cytokine analysis, and in vivo analysis of live mammary epithelial cells for mitochondrial membrane and glucose uptake to track the molecular action of metformin chemoprevention in overweight and obese women at high-risk for triple-negative breast cancer. Women are enrolled in a 300 person ALLIANCE randomized, placebo controlled chemoprevention trial. Our studies to date have shown that overweight and obese women have activation of Akt/mTOR and IL6 /Stat3 epithelial activation, epithelial glucose uptake and increased mitochondrial membrane potential, and increased mammary tissue IL6/insulin. Conclusion: These studies show our ability to directly track the molecular response to metformin chemoprevention. Note: This abstract was not presented at the conference. Citation Format: Victoria Seewaldt, James Marshall. Molecular tracking of metformin chemoprevention in a 300-person ALLIANCE randomized placebo controlled trial in women at high risk for triple-negative breast cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A16.