Abstract Background: Chronic stress as a result of residing in neighborhoods with higher levels of racial/ethnic segregation may increase a woman's risk of breast cancer. There is strong evidence of increased breast cancer risk due to social stress from animal models. Furthermore, epidemiologic studies have suggested links between racial/ethnic segregation and poor breast cancer outcomes. While a limited number of studies have demonstrated increased breast cancer risk and worse prognostic factors for African American women residing in neighborhoods with high racial/ethnic segregation compared to White women, no studies have examined this potential association in other racial/ethnic groups. Methods: Using data from the Multiethnic Cohort (MEC) (1993-2014), we examined the association between a neighborhood segregation typology of racial/ethnic compositions and incidence of primary, invasive breast cancer in a population-based sample of 101,811 African American, Japanese American, Latina, Native Hawaiian, and White women primarily residing in Los Angeles County, California and Hawaii. Segregation typology was based on the distribution of racial/ethnic groups across census tracts and linked to participants' geocoded baseline residential addresses. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer risk were estimated using multivariable Cox proportional hazards regression adjusted for age, family history of breast cancer, reproductive and lifestyle risk factors for breast cancer, and stratified by state and self-reported race/ethnicity. For each state and racial/ethnic group, the reference typology was specific to co-ethnic residents. Results: A median follow-up of 20 years yielded 6,398 breast cancer cases. In California, African American women living in predominantly White neighborhoods had reduced risk of breast cancer (HR=0.68, 95%CI=0.46-0.99) compared to African American women living in predominantly Black neighborhoods. Among Latina women, compared to residents in predominately Latino neighborhoods, those in mixed White and Asian American/Pacific Islander (AAPI) (HR=1.54, 95%CI=1.05-2.25) and multiethnic White neighborhoods (HR=1.34, 95%CI=1.07-1.69) had increased risk of breast cancer. In Hawaii, Native Hawaiian women in predominantly AAPI neighborhoods had increased breast cancer risk (HR=1.20, 95%CI=1.04-1.38) compared to Native Hawaiian women in mixed White and AAPI neighborhoods. For Japanese American women in Hawaii, those living in mixed Native Hawaiian (HR=1.28, 95% CI=1.05-1.55) and multiethnic (HR=1.61, 95% CI=1.36-1.90) neighborhoods had higher breast cancer risk than those living in predominately Asian neighborhoods. Conclusion: This large-scale prospective study in a multiethnic population found differential associations between neighborhood racial/ethnic segregation and breast cancer risk by state of residence and self-reported race/ethnicity. Future research should aim to identify pathways through which segregation measures influence breast cancer risk in specific racial/ethnic populations. Citation Format: Meera Sangaramoorthy, Joseph Gibbons, Juan Yang, Katherine Lin, Yuqing Li, Jenna A Khan-Gates, Pushkar Inamdar, Christopher A. Haiman, Loïc Le Marchand, Lynne R Wilkens, Scarlett L. Gomez, Salma Shariff-Marco, Iona Cheng. Neighborhood segregation typology 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-175.