Abstract Introduction: Neighborhood disadvantage has been shown to independently predict breast cancer specific survival even after considering access to care barriers. This effect may be explained in part by biologic influences of the neighborhood environment on breast tumors. Social genomics literatures posits that this relationship is mediated by chronic stress in the form of social adversity, i.e. disadvantaged neighborhoods may be leading to increased stress for patients which in turn may effect tumor biology. Our objective in this study was to link a measure of patient-reported neighborhood specific stress with an objective and widely used measure of neighborhood disadvantage, the Area Deprivation Index (ADI). Methods: In this prospective cohort study patients with stage I-IV breast cancer completed survey questions from a validated Neighborhood Social Environment Adversity Survey (NSEAS) to measure perceived stress caused by their environment. Questions included both 5-item and 4-item Likert scale answer choices with higher scores indicating higher stress. Responses were standardized into Z-scores and composite and subscale scores were calculated by summation. Subscales included threat to safety, social cohesion, and aesthetic quality. Survey questions demonstrated good reliability with a Cronbach’s α of 0.72. Cohort addresses were used to determine the ADI, a continuous measure from 1-10 with higher scores indicating more disadvantage. Hierarchical linear regression was used to assess the relationship between ADI and NSEAS composite and subscale scores while controlling for covariates. Results: 380 breast cancer patients completed the NSEAS 61.6% were Hispanic, 17.0% were Non-Hispanic White, and 21.4% were Non-Hispanic Black. Mean age (SD) was 56 (12) years. Mean (SD) ADI was 4 (3). On univariate analysis, we found that ADI significantly predicts NSEAS composite and subscale scores (Composite β =0.63, t=5.68, p< 0.001; Threat to Safety β =0.18, t=5.07, p< 0.001; Social Cohesion β =0.19, t=3.35, p< 0.001; Aesthetic Quality β =0.15, t=4.20, p< 0.001). After controlling for age, race, ethnicity, highest education level, patient insurance, and annual household income, we found that ADI continued to significantly predict levels of NSEAS (Composite β =0.48, t=4.02, p< 0.001; Threat to Safety β =0.14, t=3.57, p< 0.001; Social Cohesion β =0.14, t=2.34, p=0.02; Aesthetic Quality β =0.12, t=3.09, p=0.002). Conclusion: In our novel study, we found that higher levels of neighborhood disadvantage independently predict higher levels of perceived neighborhood stress in breast cancer patients. Because of the known detrimental effects of both chronic stress and neighborhood disadvantage on health, understanding the specific factors of stress caused by neighborhood-level social adversity can help define targetable areas of intervention for future studies. These findings contribute to current literature on how and why neighborhood disadvantage leads to worse breast cancer outcomes. Table 1. Hierarchical Regression Illustrating Relationship between Neighborhood Disadvantage and Patient-Reported Neighborhood Social Environment Adversity Survey Scores Citation Format: Alexandra Hernandez, Maya Lubarsky, Susan Kesmodel, Michael Antoni, Neha Goel. Neighborhood Disadvantage and Social Adversity in Breast Cancer Patients [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 PO2-09-07.