Air Pollution, Clustering of Particulate Matter Components, and Breast Cancer in the Sister Study: A U.S.-Wide Cohort

BACKGROUND: Particulate matter (PM) is a complex mixture. Geographic variations in PM may explain the lack of consistent associations with breast cancer. OBJECTIVE: We aimed to evaluate the relationship between air pollution, PM components, and breast cancer risk in a United States-wide prospective cohort. METHODS: We estimated annual average ambient residential levels of particulate matter [Formula: see text] and [Formula: see text] in aerodynamic diameter ([Formula: see text] and [Formula: see text] , respectively) and nitrogen dioxide ([Formula: see text]) using land-use regression for 47,433 Sister Study participants (breast cancer–free women with a sister with breast cancer) living in the contiguous United States. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk associated with an interquartile range (IQR) increase in pollutants. Predictive k-means were used to assign participants to clusters derived from [Formula: see text] component profiles to evaluate the impact of heterogeneity in the [Formula: see text] mixture. For [Formula: see text] , we investigated effect measure modification by component cluster membership and by geographic region without regard to air pollution mixture. RESULTS: During follow-up ([Formula: see text]), 2,225 invasive and 623 ductal carcinoma in situ (DCIS) cases were identified. [Formula: see text] and [Formula: see text] were associated with breast cancer overall [[Formula: see text] (95% CI:0.99, 1.11) and 1.06 (95% CI:1.02, 1.11), respectively] and with DCIS but not with invasive cancer. Invasive breast cancer was associated with [Formula: see text] only in the Western United States [[Formula: see text] (95% CI:1.02, 1.27)] and [Formula: see text] only in the Southern United States [[Formula: see text] (95% CI:1.01, 1.33)]. [Formula: see text] was associated with a higher risk of invasive breast cancer among two of seven identified composition-based clusters. A higher risk was observed [[Formula: see text] (95% CI: 0.97, 1.60)] in a California-based cluster characterized by low S and high Na and nitrate ([Formula: see text]) fractions and for another Western United States cluster [[Formula: see text] (95% CI: 0.90, 2.85)], characterized by high fractions of Si, Ca, K, and Al. CONCLUSION: Air pollution measures were related to both invasive breast cancer and DCIS within certain geographic regions and PM component clusters. https://doi.org/10.1289/EHP5131