548 Background: Obesity increases breast cancer recurrence and mortality. Strategies that induce weight loss may improve clinical outcomes. We investigated the feasibility and efficacy of personalized energy restricted PBD plus Ex on weight and body composition in primary HR-positive breast cancer (NCT04298086). Methods: Postmenopausal women with body mass index (BMI) ≥ 27 kg/m2 on adjuvant endocrine therapy were randomized (1:1) to PBD plus Ex or attention control for 24 weeks. PBD plus Ex received individualized caloric goals adjusted weekly to target 1.5 lbs/week weight loss. PBD targeted 500 kcal/day goal deficit achieved via nutrition coaching and meal delivery. Ex sessions targeted 250 kcal goal expenditure via remotely delivered treadmill walking 3-5 days/week with real-time monitoring. Attention control received a home treadmill and monthly check-in calls. Baseline to post-intervention changes in weight and body composition, measured by dual energy X-ray absorptiometry (DXA), were compared between arms using linear mixed models. Results: 43 women were randomized between 8/2020 and 4/2023. Weight data was available for all participants (35 measured at follow-up, 8 abstracted from clinical documentation); 37 completed post-intervention DXA. At baseline, mean BMI was 34 (SD 4) kg/m2. Intention-to-treat results are presented in the Table. Mean weight loss in PBD plus Ex was –13% (SD 6%) compared with –5% (SD 6%) in attention control (mean between group difference –8 kg, 95% CI –11, –4). Mean fat loss in PBD plus Ex was –6 kg compared with –2 kg in attention control (mean between group difference –4 kg, 95% CI –6, –2). Lean mass increases were greater in PBD plus Ex (P<0.001). Weekly energy deficit goal compliance was 95% in month 1 and 64% in month 6. No serious adverse events were observed. Baseline and post-intervention tissue samples were available on 37 (86%) patients, which will undergo biologic correlative analysis. Conclusions: Personalized PBD plus Ex led to substantial weight loss and favorable changes in body composition during endocrine therapy for HR-positive breast cancer. Clinical trial information: NCT04298086 . [Table: see text]