Purpose. The purpose of this study was to evaluate acute locoregional toxicity in patients with breast cancer receiving concurrent metformin plus radiation therapy. Methods and Materials. Diabetic breast cancer patients receiving concurrent metformin and radiation therapy were matched with nondiabetic patients and diabetic patients using an alternative diabetes medication. Primary endpoints included the presence of a treatment break and development of dry or moist desquamation. Results. There was a statistically significant increase in treatment breaks for diabetic patients receiving concurrent metformin when compared to the nondiabetic patients ( value = 0.02) and a trend toward significance when compared to diabetic patients receiving an alternate diabetes medication ( value = 0.08). Multiple logistic regression analysis demonstrated concurrent metformin use as being associated with a trend toward the predictive value of determining the incidence of developing desquamation in diabetic patients receiving radiation therapy compared to diabetic patients receiving an alternate diabetes medication ( value = 0.06). Conclusions. Diabetic patients treated with concurrent metformin and radiation therapy developed increased acute locoregional toxicity in comparison with diabetic patients receiving an alternate diabetes medication and nondiabetic patients. Further clinical investigation should be conducted to determine the therapeutic ratio of metformin in combination with radiation therapy. 1. Introduction Diabetes mellitus (DM) is a common endocrinopathy that has been shown to increase the incidence of multiple types of cancer, including breast cancer. This may stem from the upregulation of both the insulin receptor and insulin-like growth factor receptor, which promotes a dual survival and proliferation advantage through targets of the phosphatidylinositol 3-kinase/serine/threonine kinase AKT signaling pathway and activation of the mitogen kinases, MEK, and ERK, respectively [1, 2]. Metformin, a biguanide, is a first-line therapeutic agent that has been used for over 30 years in the treatment of DM. Multiple case-control analyses have demonstrated a significantly lower incidence of breast cancer in diabetic patients receiving metformin [3, 4]. The anticancer mechanism of metformin is not fully understood, but Towler and Hardie describe its involvement in the suppression of hepatic gluconeogenesis and activation of AMP-activated protein kinase (AMPK) [5]. Increased levels of AMPK reduce insulin and IGF-I signaling downstream of the receptor, therefore reducing
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