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Background  Exposure to certain outdoor air pollutants may be associated with a higher risk of breast cancer, though potential underlying mechanisms are poorly understood. We examined whether outdoor air pollution was associated with involution of terminal duct lobular units (TDLUs), the histologic site where most cancers arise and an intermediate marker of breast cancer risk.    Methods  Pathologist-enumerated TDLUs were assessed in H&E (hematoxylin and eosin)-stained breast tissue sections from 1904 US women ages 18–75 who donated to the Susan G. Komen Tissue Bank (2009–2012). The 2009 annual fine particulate matter < 2.5 μm in diameter (PM 2.5 ) total mass (μg/m 3 ) at each woman’s residential address was estimated from the Environmental Protection Agency’s Downscaler Model combining Community Multiscale Air Quality (CMAQ) System modeling with air quality monitoring data. We secondarily considered CMAQ-modeled components of PM 2.5  and gaseous pollutants. We used  K -means clustering to identify groups of individuals with similar levels of PM 2.5  components, selecting groups via cluster stability analysis. Relative rates (RRs) and 95% confidence intervals (95% CIs) for the association between air pollutants and TDLU counts were estimated from a zero-inflated negative binomial regression model adjusted for potential confounders.    Results  PM 2.5  total mass was associated with higher TDLU counts among all women (interquartile range (IQR) increase, RR = 1.06; 95% CI: 1.01–1.11). This association was evident among both premenopausal and postmenopausal women (premenopausal RR = 1.05, 95% CI: 1.00–1.11; postmenopausal RR = 1.11, 95% CI: 1.00–1.23). We identified 3 groups corresponding to clusters that varied geographically and roughly represented high, medium, and low levels of PM 2.5  components relative to population mean levels. Compared to the cluster with low levels, the clusters with both high (RR = 1.74; 95% CI: 1.08–2.80) and medium (RR = 1.82; 95% CI: 1.13–2.93) levels were associated with higher TDLU counts; although not significantly different, the magnitude of the associations was stronger among postmenopausal women.    Conclusions  Higher PM 2.5  levels were associated with reduced TDLU involution as measured by TDLU counts. Air pollution exposure may influence the histologic characteristics of normal tissue which could in turn affect breast cancer risk.

Outdoor air pollution and terminal duct lobular involution of the normal breast