ABSTRACT Research has shown that a weight loss of >10% favorably modulates biomarkers of breast cancer risk. The most effective behavioral weight loss programs, such as the Diabetes Prevention Program (DPP), yield weight losses of only 4-7%. As a result, many people resort to weight-loss surgery, which is costly, drastic, and an often irreversible choice that, when successful, results in weight losses of 25-50%, which far exceed that necessary for risk reduction. New behavioral strategies that enhance the weight-loss outcomes of existing interventions are needed. One recently introduced and innovative weight-loss strategy is `Hunger Training'. Hunger Training uses real-time blood glucose monitoring as biological feedback to help users self-regulate meal initiation to promote sustained weight loss that may have indirect and direct effects on breast cancer risk reduction. Evidence demonstrates that Hunger Training alone?without any additional dietary restrictions or increased physical activity?produces weight losses of >7% and significantly improves insulin sensitivity. In the proposed pilot study, we will combine Hunger Training with the DPP using a two-arm approach. We will randomize 50 non-diabetic, postmenopausal obese women, identified as being at high risk for breast cancer and enrolled in the MD Anderson Longitudinal High Risk Breast Cohort for ?1 year, to receive either the DPP only or the DPP-plus-Hunger Training for 16 weeks. Aim 1 is to evaluate the feasibility of adding Hunger Training to the DPP. Feasibility criteria will include accrual rates >50%, attrition rates <20%, and protocol adherence rates >75% for both study groups. Aim 2 is to estimate the magnitude of the effect sizes and variation in the outcome variables for the DPP-only and DPP-plus-Hunger Training interventions on changes in weight; metabolic and breast cancer risk biomarkers (e.g., fasting insulin and glucose levels, levels of glycosylated hemoglobin, insulin resistance, adiponectin, interleukin-6, and c-reactive protein); and proposed behavioral mediators (e.g., reduction in total energy intake, overall eating frequency, percent of eating events occurring at or below the average fasting blood glucose concentration). This study will be the first to assess the synergistic effect of adding Hunger Training to a highly disseminated weight-loss intervention. We expect to find that the addition of Hunger Training to the DPP is feasible and that the combined intervention has an additive effect on promoting weight losses of >10% in obese women at risk for postmenopausal breast cancer. The successful completion of this pilot study will support a larger randomized controlled trial that will additionally enable us to compare the DPP's long-term impact on weight loss and weight loss maintenance to that of the DPP-plus-Hunger Training.