Abstract Background: Measurements (amount, distribution, and radiodensity) of muscle and adipose tissue were reported to be individually associated with overall survival in breast cancer survivors, but they were not typically combined to develop an overall risk score. Such a score can identify patients at high risk of death and prioritize patients in need of lifestyle interventions. Objectives: We developed a novel body composition risk score (B-Score) by combining multiple tissue measurements. Methods: We included 3105 patients with stage II or III breast cancer (diagnosed from 2000 to 2013) at Kaiser Permanente Northern California and Dana Farber Cancer Institute. From CT scans at diagnosis, we used the third lumber vertebrae as the landmark to assess areas (cm2) and radiodensity (HU) of muscle and adipose tissue. We divided the area by height2 (m2) to derive the index and measured the average HU of the tissue area as the radiodensity, which acts as a marker of tissue 'quality' to be indicative of lipid content, inflammation, and angiogenesis. Out of all tissue measurements, we considered skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI) and SAT radiodensity as they were independent predictors for overall survival. Each measurement was dichotomized using optimal stratification, with low SMI (< 40.1cm2/m2), high SATI (≥75.7cm2/m2), and high SAT radiodensity (≥ -97.2HU) considered risk factors. We calculated B-Score as the sum of these factors and estimated its association with overall survival using Cox proportional hazards regression with adjustment for clinicopathologic factors. Results: Mean (standard deviation) age at diagnosis was 53.9 (11.8) years, 2161 (70.1%) were Non-Hispanic White, 1880 (60.5%) were stage II, and 919 (29.6%) died over a median follow-up of 10.7 years. Most patients (60.6%) had only one body composition risk factor (B-Score = 1). Compared to those with no body composition risk factors (B-Score = 0), the risk of death increased with more body composition risk factors: the adjusted hazard ratios were 1.10 (95% CI: 0.85, 1.42), 1.47 (95% CI: 1.12, 1.92), and 2.11 (95% CI: 1.26, 3.53) for B-Scores of 1, 2, and 3, respectively (Ptrend < 0.001). Conclusions: More unfavorable body composition characteristics were associated with increased risks of overall mortality in a dose-response manner. Considering body composition measurements together as a composite score (B-Score) may prove a useful tool to identify patients at high risk of death following breast cancer diagnosis. Table. Adjusted Associations of the Body Composition Risk Score (B-Score) with Overall Mortality Among Patients with Early-Stage Breast Cancer Abbreviations: HR, hazard ratio. a Areas (cm2) and radiodensity (HU) of skeletal muscle and subcutaneous adipose tissue (SAT) were extracted from the single axial CT slice at the third lumbar vertebra. The body composition risk score was defined as the sum of three risk factors: low skeletal muscle index (SMI; <40.1cm2/m2), high SAT index (SATI; ≥75.7cm2/m2), and high SAT radiodensity (≥ -97.2HU). b Adjusted for age (years), race and ethnicity (Asian, Black, Hispanic, Non-Hispanic White, and Others), stage (II, III), ER (ER+, ER-), PR (PR+, PR-), HER2 (HER2+, HER2-, unknown), smoking (current, former, never), Charlson comorbidity index (0, 1-2, ≥3), and BMI (<18.5, 28.5-24.9, 25-29.9, and ≥30 kg/m2). For the trend test, B-Score was considered as a continuous variable with adjustment for the above covariates. Citation Format: En Cheng, Bette Caan, Wendy Chen, Carla Prado, Elizabeth Cespedes Feliciano. A Novel Body Composition Risk Score (B-Score) and Overall Survival among Patients with Early-Stage Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-11.