Airborne metals, polycyclic aromatic hydrocarbons 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: 2021

Abstract Body:
Purpose: Terminal duct lobular units (TDLUs) are the site where most breast cancers arise and lack of TDLU involution is associated with increased breast cancer risk. Our prior work demonstrated that particulate matter <2.5 microns in diameter (PM2.5) was associated with reduced involution. In this study, we sought to identify the association for other airborne pollutants, including metals and polycyclic aromatic hydrocarbons (PAHs). Methods: Measures of TDLU involution (TDLU count, span, and acini/TDLU) were enumerated in the breast tissue of 1,904 women who donated a normal sample to the Komen Tissue Bank. Women's residence at donation was geocoded and linked to the National Air Toxics Assessment database to estimate concentrations of airborne PAHs and 9 metals (antimony, arsenic, cadmium, chromium, cobalt, lead, mercury, nickel, & selenium) near their residence. We evaluated associations per interquartile range (IQR) increase and with quartile-based categories of pollutants. Zero-inflated negative binomial regression was used to estimate adjusted relative rates (RRs) and 95% confidence intervals (95% CIs) for TDLU counts. Ordinal logistic regression was used to estimate adjusted odds ratios and 95% CIs for tertiles of TDLU span and acini/TDLU. Quantile g-computation was used to examine the joint impact of a simultaneous quartile increase in all 10 pollutants with TDLU count. Results: Antimony was associated with higher TDLU counts non-monotonically across categories (e.g. 2nd vs 1st category RR= 1.24, 95% CI: 1.06-1.46; 4th vs 1st category RR=1.09, 95% CI: 0.93-1.29) and per IQR increase (RR=1.02, 95% CI: 1.00-1.04). There was little evidence supporting an association for other individual pollutants and TDLU count, and none were related to acini/TDLU. A few pollutants (PAHs, arsenic, lead, mercury, nickel, and selenium) were associated with reduced odds of longer TDLU span. The joint association for the 10 pollutants was negligible (RR=0.96, 95% CI: 0.89-1.05). Conclusions: This work provides little support for an association between airborne metals and PAHs, individually or as a mixture, and measures of TDLU involution. Other airborne pollutants, such as PM2.5, may be more relevant for early histologic changes in breast tissue related to breast cancer.

Keywords: Metals, polycyclic aromatic hydrocarbons, terminal duct lobular units, breast cancer