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Air pollution contains numerous carcinogens and endocrine disruptors which may be relevant for breast cancer. Previous research has predominantly been conducted in White women; however, Black women may have higher air pollution exposure due to geographic and residential factors. We evaluated the association between air pollution and breast cancer risk in a large prospective population of Black women. We estimated annual average ambient levels of particulate matter <2.5 μm (PM 2.5), nitrogen dioxide (NO 2) and ozone (O 3) at the 1995 residence of 41,317 participants in the Black Women's Health Study who resided in 56 metropolitan areas across the United States. Cox proportional hazards regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for an interquartile range (IQR) increase in each pollutant. We evaluated whether the association varied by menopausal status, estrogen receptor (ER) status of the tumor and geographic region of residence. With follow-up through 2015 (mean = 18.3 years), 2146 incident cases of breast cancer were confirmed. Higher exposure to NO 2 or O 3 was not associated with a higher risk of breast cancer. For PM 2.5 , although we observed no association overall, there was evidence of modification by geographic region for both ER- (p for heterogeneity = 0.01) and premenopausal breast cancer (p for heterogeneity = 0.01). Among women living in the Midwest, an IQR increase in PM 2.5 (2.87 μg/m3), was associated with a higher risk of ER- (HR = 1.53, 95% CI: 1.07–2.19) and premenopausal breast cancer (HR = 1.32, 95% CI: 1.03–1.71). In contrast, among women living in the South, PM 2.5 was inversely associated with both ER- (HR = 0.74, 95% CI: 0.56–0.97) and premenopausal breast cancer risk (HR = 0.75, 95% CI: 0.62–0.91). Overall, we observed no association between air pollution and increased breast cancer risk among Black women, except perhaps among women living in the Midwestern US. • This study builds on a large prospective nationwide cohort of Black women in the US. • There was no association between air pollution and breast cancer risk overall. • For PM 2.5 , a heterogeneous exposure, associations varied by geographic region. • In the Midwest, PM 2.5 was associated with risk of both ER- and premenopausal cancer. • In the South, PM 2.5 was inversely associated both ER- and premenopausal cancer. [ABSTRACT FROM AUTHOR]