Air pollution and terminal duct lobular involution of the normal breast

Authors: Niehoff NM, Keil AP, Jones RR, Fan S, Gierach GL, White AJ

Category: Molecular Epidemiology & Environment
Conference Year: 2020

Abstract Body:
Purpose: Air pollution has been associated with a higher risk of breast cancer. We examined whether air pollution was associated with involution of terminal duct lobular units (TDLUs), the histologic site where most breast cancers arise and an intermediate marker of breast cancer risk. Methods: Pathologist enumerated TDLUs (i.e., TDLU count, a metric inversely associated with involution), were assessed in H&E (Hematoxylin and Eosin)-stained breast tissue sections from 1,908 United States-residing women ages 18-75 who donated to the Susan G. Komen Tissue Bank (2009-2012). The 2009 annual PM2.5 total mass (µg/m3) at each woman's residential address was estimated from the Environmental Protection Agency's Downscaler Model that combines Community Multiscale Air Quality (CMAQ) System modeling data with air quality monitoring data. We secondarily considered CMAQ-modeled components of PM2.5 and gaseous pollutants. We used K-means clustering to identify groups of individuals with similar levels of PM2.5 components, selecting 3 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 confounders. Results: PM2.5 total mass was associated with higher TDLU count among all women (interquartile range (IQR) increase, RR=1.03; 95% CI: 1.00-1.06). The magnitude of the PM2.5-TDLU count association was stronger among postmenopausal women (RR=1.10; 95% CI: 1.03-1.18). Using K-means, we identified 3 groups that corresponded to clusters that varied geographically and roughly represented high, medium, and low levels of PM2.5 components. Compared to the cluster with low levels, the clusters with both high (RR=1.25; 95% CI: 0.95- 1.63) and medium (RR=1.24; 95% CI: 0.95-1.62) levels were associated with higher TDLU counts; associations were again stronger among postmenopausal women. Conclusions: Higher PM2.5 was associated with reduced TDLU involution as measured by TDLU counts. Air pollution may influence the histologic characteristics of normal tissue which could in turn affect breast cancer risk. This may be particularly relevant for the breast tissue of postmenopausal women.

Keywords: air pollution, terminal duct lobular units, breast cancer