Air Pollutants and Breast Cancer Risk: A Parallel Analysis of Five Large US Prospective Cohorts

<b>Objectives.</b> To determine whether outdoor air pollution exposure is associated with breast cancer incidence. <b>Methods.</b> Residential-level concentrations of nitrogen dioxide (NO₂, parts per billion [ppb]), fine particulate matter (PM_2.5; ≤ 2.5 μ/m³) and ozone (ppb) in the United States were estimated for participants of the Nurses' Health Studies, Women's Health Initiative Clinical Trials and Observational Study Cohort, and Sister Study using high-resolution spatiotemporal models. Cox proportional hazards regression estimated cohort-specific hazard ratios (HRs) and 95% confidence intervals (CIs), and a random effects model determined summary HRs, overall and by estrogen receptor (ER)/progesterone receptor (PR) subtype and census region. <b>Results.</b> NO₂ was positively associated with overall breast cancer incidence (n = 28 811 cases; HR = 1.03; 95% CI = 1.00, 1.05), with little variation by subgroups. PM_2.5 was associated with higher incidence of ER-/PR- tumors (n = 2367 cases; HR = 1.14; 95% CI = 1.04, 1.24; <i>P</i>-heterogeneity < .001) and with higher overall incidence in the Midwest (HR = 1.15; 95% CI = 1.01, 1.32; <i>P</i>-heterogeneity = .01). Ozone was not associated with overall incidence, but was associated with ER-/PR- tumors (n = 3406 cases; HR = 1.10; 95% CI = 1.00, 1.21; <i>P</i>-heterogeneity = .03). <b>Conclusions.</b> In this largest US study to date, we confirmed an association between NO₂ and breast cancer, and we present novel associations of PM_2.5 and ozone with ER-/PR- tumors. (<i>Am J Public Health</i>. 2025;115(12): 2030-2043. https://doi.org/10.2105/AJPH.2025.308247).