Abstract Introduction: Residential segregation has been documented to contribute to health inequities. The Index of Concentration at the Extremes (ICE) is a local measure of residential segregation that can capture economic, racial, and combined racialized economic residential segregation. ICE measures have only recently been examined in cancer studies, few of which have focused on breast cancer risk and none among Asian American or Pacific Islander (AAPI) groups. In the Multiethnic Cohort Study (MEC), we examined the associations of neighborhood ICE measures with breast cancer incidence among 101,811 female participants in five racial/ethnic groups (African American, Latino, Japanese American, Native Hawaiian, and White). Methods: ICE measures were developed based on 1990 U.S. census tract-level data, categorized in quintiles based on Los Angeles county and Hawai'i state-specific distributions, and assigned to the residential census tract of MEC female participants residing, at study baseline, in California (CA) (primarily Los Angeles, n=56,880), and Hawai'i (HI) (n=44,931). Separate ICE measures were created for household income, education, race/ethnicity, and combined household income and race/ethnicity. Women, aged 45-75 at enrollment, completed a comprehensive lifestyle questionnaire and were followed from baseline (1993-1996) to earliest date of invasive breast cancer diagnosis (n=6,398), death, or end-of-follow-up (12/31/2014). Invasive breast cancer incidence was modeled using Cox proportional hazards regression adjusted for demographics, family history of breast cancer, reproductive and lifestyle factor factors. Stratified analyses were conducted by race/ethnicity and stage at diagnosis. Results: For women in CA MEC, there were significantly higher risks of breast cancer for those living in neighborhoods with more versus less concentrated privilege [Q5 v Q1 Hazard Ratios (HR): ICE income 1.16 (1.03-1.31), ICE education 1.21 (1.05-1.39)]. In stratified analyses, these patterns of associations were seen for African Americans, Latinos, and Japanese Americans. Risks were also higher among Japanese American women living in neighborhoods with greater concentrations of Whites versus AAPI [Q5 v Q1 ICE Race HR: 1.77 (1.22-2.57)] and for Latino women living in neighborhoods with greater concentrations of high income-White households versus low income-Hispanic households [Q4 v Q1 ICE Race + Income HR: 1.48 (1.20-1.82)]. For women in HI MEC, those living in neighborhoods with higher versus lower ICE income or ICE education had higher risk of localized stage at diagnosis and lower risk of regional & distant diagnosis (p Het <0.01). No associations were found among White or Native Hawaiian women. Conclusions: Our findings suggest economic residential segregation plays an important role in breast cancer risk among African American, Latino, and Japanese American women. This study also highlights the importance of examining racial and racialized economic residential segregation separately across racial/ethnic groups. Citation Format: Jenna Khan-Gates, Salma Shariff-Marco, Katherine Lin, Pushkar Inamdar, Juan Yang, Yuqing Li, Meera Sangaramoorthy, Christopher Haiman, Loïc Le Marchand, Lynne R Wilkens, Scarlett L Gomez, Iona Cheng. Local economic and racial/ethnic segregation and breast cancer risk: The Multiethnic Cohort Study [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-171.