Abstract Asian Americans (AAs) are the only racial/ethnic group in the United States for whom cancer is the leading cause of death. In AA women, the rate of breast cancer (BC) has significantly increased in the past two decades. However, the reasons behind the observed increase in risk are not well understood. The All of Us (AoU) Research Program aims to enroll one million participants nationwide, focusing on including individuals from diverse backgrounds, to advance precision health research. The goal of this pilot study was to evaluate the feasibility of using AoU data to analyze factors potentially associated with breast cancer risk in AAs and to develop enhanced breast cancer prediction models. There were 3,433 self-reported AA women with available genomic data. In addition to the genomic data, data was available from surveys, participants’ electronic health records (EHRs), and physical measurements taken at the time of their study visit. BC cases were identified by self-report on surveys (n=38), EHR diagnosis data (n=104), or both survey and EHR (n=59), totaling 201 cases identified. Of these, only 17 were incident cases. Of the 163 cases detected in the EHR, 96.3% were invasive BCs, and the median age at diagnosis was 54.2 (±12.6) years. Among the 38 survey-only-identified cases, age at diagnosis was unclear due to the large age ranges (e.g.18-64 years) in the categories presented in the survey. For purposes of the case-control analysis, five AA women with no BC diagnosis were matched to each BC case by age group and geographic region. Body mass index, annual household income, marital status, history of alcohol consumption, and history of cigarette smoking and vaping were not statistically significantly different between cases and controls (a=0.05). One third (34.3%) of cases were born in the U.S. and 65.2% were born in another country vs. 25.0% and 74.0% of controls, respectively (p= 0.01). Employment status was also different, with 50.8% of cases being unemployed vs. 42.0% of controls (p=0.02). There appeared to be a difference in first-degree family history of BC (reported in 8% of cases vs. 5% of controls) although the results were not statistically significant (p=0.08). However, family history of BC data was not available for 43.3% and 51.0% of the cases and controls, respectively. Gynecologic factors, such as ages at menarche and menopause, and hormone use, were not asked in the surveys and were not widely captured in the EHR data. In our analysis of nine BC- associated genes (BRCA1, BRCA2, ATM, TP53, PTEN, CHEK2, CDH1, PALB2, STK11), pathogenic variants were identified in 1.0% of cases and 0.7% of controls. In summary, the AoU data set enables the study of a diverse national cohort with rich genomic data. However, the low representation of AAs, small numbers of incident cases, limited data on personal gynecologic history, cancer family history and social determinants of health, and broad categorization of age at diagnosis present challenges to using this data to build accurate and effective risk prediction models for BC risk in AAs. Citation Format: Catalina Haas Garcia, Wen-Pin Chen, Danni Liu, Alice W Lee, Min Zhang, Argyrios Ziogas, Sora Tanjasiri, Hannah Lui Park. Feasibility of using data from the All of Us Research Program to better understand Asian American breast cancer risk [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A103.