Background: The majority of women diagnosed with breast cancer are overweight or obese, and gain weight with treatment, leading to inferior survival outcomes. The Practice-based Opportunities for Weight Reduction (POWER) investigators reported that, in an obese population with cardiovascular risk factors, a scalable remote-based weight loss intervention was equally effective to an in-person intervention (Appel NEJM 2011). We have adapted the remote intervention for breast cancer survivors. Methods: Randomized phase II single-blinded trial. Participants are women with stage 0-III breast cancer and a BMI ≥ 25 who have completed local therapy and adjuvant chemotherapy. Objectives:1.) Compare the proportion of participants who lose ≥5% of their baseline body weight after 6 and 12 months in the POWER-remote and self-directed (control) arms; 2.) Investigate the effects of weight loss on a panel of biomarkers relevant to obesity, inflammation, and breast cancer risk (insulin, IGF-1, hsCRP, IL-1, IL-6, TNF-α, leptin, adiponectin, estradiol, and telomere length); 3.) Investigate the effects of weight loss on patient-reported outcomes (PROs), particularly physical function. Statistical Approach: We hypothesize that the proportion of women who experience ≥5% weight loss after 6 months will be greater in POWER-remote and will be similar to the results of the original POWER study (38.2% and 18.8% ≥5% weight loss in the remote and control groups, respectively). An interim futility analysis is planned after the first 80 patients are evaluable for the primary endpoint. The final analysis will conclude a significant benefit from POWER-remote if the one-sided p value is greater than 0.10 by Fisher’s exact test. Changes in biomarkers and PROs from baseline to 6 months will be calculated and tested for differences by treatment arm and by response. We have enrolled 16 of the planned 200 patients. Future Directions: Results will be used to implement clinically based weight loss programs, and biomarker data will improve our understanding of energy dynamics in breast cancer survivors, leading to future studies investigating weight loss for primary and secondary breast cancer prevention. Clinical trial information: NCT01871116.