Associations of Hazardous Air Pollutants with Breast Cancer Subtypes among Women in Metropolitan Chicago

Hazardous air pollutants (HAP’s) are pollutants known to cause or suspected of causing cancer or other serious health effects. These include non-endocrine and endocrine disrupting (ED) metallics and non-metallics. ED chemicals mimic, block, or interfere with hormones in the body’s endocrine system and have been associated with a variety of human health issues including breast cancer (BC). Metallics are individual metals and metal compounds that are persistent in the environment and can negatively impact human health through accumulation in tissue. Many factors influence patterns of exposure to HAP’s, and resulting negative health outcomes such as BC. While there are established risk factors for BC including genetic and behavioral factors, they only explain half of all cases observed in the U.S. Recently, environmental air pollution has been hypothesized as a previously understudied risk factor for BC risk, especially in urban areas. The goal of this study was to examine differences in HAP burden and better understand the associations of individual HAP’s and mixtures of HAP’s with invasive and hormone receptor (HR) negative BC among a cohort of women in metropolitan Chicago. First, differences in the distribution of census tract level HAP’s were examined by race/ethnicity and segregation among women in the Metropolitan Chicago Breast Cancer Registry (MCBCR) cohort. The Environmental Protection Agency’s (EPA) National Air Toxics Assessment (NATA) data was used to obtain census tract level measures of inhalation exposures to 60 HAP’s that are known or suspected mammary gland carcinogens. Percentage of African American (AA) individuals residing in each census tract was used to define segregated versus non-segregated tracts. Concentrations of HAP’s were examined among non-Hispanic White (nHW) women, AA women, Hispanic women, AA women residing in non-segregated tracts, and AA women residing in segregated tracts. We observed that minority women were more likely to reside in census tracts with higher levels of exposure to HAP’s as compared to their nHW counterparts, and that among AA women, those who resided in segregated tracts fared worse with regards to their exposure. Next, individual associations of HAP’s with 3 and 5-year lagged invasive and HR negative BC were examined among women enrolled in MCBCR in 2002, 2005, and 2011, to match the time of NATA data collection. Many positive and inverse associations were identified. For certain HAP’s, associations were consistent regardless of lag time, outcome, or cohort, however for other HAP’s estimates varied substantially and in some cases qualitatively. In general, ED metallics and non-metallics were observed to be associated with a higher incidence of HR negative BC, which is more aggressive, and tends to disproportionately affect AA women. Risk factors for HR negative BC are limited and much is still unknown. As such, exposure to ED HAP’s may be an important risk factor. Associations of ED HAP’s with HR negative BC were stronger among obese, post-menopausal, and AA women. Lastly, associations of mixtures of HAP’s with 3 and 5-year lagged invasive and HR negative BC were examined using principal component analysis (PCA) and quantile g-computation (QGCOMP). Examination of mixtures is important given that individuals are exposed to a combination of HAP’s simultaneously. In quantile g-computation analyses, metallics overall were positively associated with invasive and HR negative BC across cohorts. Additionally, mixtures of ED HAP’s in particular were more strongly associated with HR negative BC. Results from PCA analyses showed positive associations of certain principal components with both invasive and HR negative BC and may be useful for pinpointing specific sources of exposure that are more hazardous than others in Chicago. Findings from this study are not only useful for better understanding environmental justice issues and associations of HAP’s with BC, but also for better understanding the utility of NATA exposure data in epidemiological studies. Our results can be used to guide policy development regarding unequal HAP exposure among minority populations. Additionally, our results indicate that HAP’s may play a role in the etiology of HR negative BC, and thus may serve as a risk factor that can be targeted in the future.