Abstract B011: Associations between county-level air pollutants and early-onset breast cancer incidence rates in the U.S

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Abstract Purpose: The incidence of early-onset breast cancer, diagnosed before age 50 years, has increased significantly in the U.S. and globally in recent decades. While various genetic factors have been implicated in the development of early-onset breast cancer, the role of environmental exposures remains unclear. This study examined associations between ambient air pollution measures and early-onset breast cancer incidence rates in the U.S. Methods: We conducted an ecological analysis of county-level associations between particulate matter <2.5 micrometers (PM2.5) and Nitrogen Dioxide (NO2) exposures (averaged from 2002-2006) and age-adjusted early-onset breast cancer rates (averaged from 2017-2021), accounting for a potential latency period between exposure and diagnosis. The study included 1,422 U.S. counties with available data on pollutants and age-adjusted early-onset breast cancer incidence rates. Generalized additive models were used to estimate associations between pollutants (PM2.5 and NO2 ) and early-onset breast cancer incidence rates, adjusting for county-level prevalence of physical inactivity, college education attainment, poverty, and proportions of Hispanic and non-Hispanic Black populations. Results: After adjusting for confounders, PM2.5 was significantly inversely associated with early-onset breast cancer rates (Tertile 2 vs. Tertile 1: b = -1.66, p=0.01; Tertile 3 vs. Tertile 1: b = -1.85, p=0.01). Similar inverse associations were observed for NO2 (Tertile 2 vs. Tertile 1: b = -1.97, p<0.01); Tertile 3 vs. Tertile 1: b=-2.59, p<0.01). A significant non-linear association between PM2.5 (per 10-unit increase) and early-onset breast cancer rates was detected (estimated degrees of freedom (EDF) = 3.2, p=0.014), with rates increasing up to approximately 10 mcg/m3, then declining at higher concentrations. Conclusion: These findings suggest inverse associations between higher tertiles of PM2.5 and NO2 exposure and early-onset breast cancer rates. However, the observed non-linear relationship between PM2.5 and early-onset breast cancer indicates a possible threshold effect or residual confounding at higher PM2.5 exposure levels. These results underscore the complexity of modeling environmental risk and highlight the need for further research to confirm these findings and investigate underlying biological mechanisms for potential threshold effects. If confirmed, the findings suggest that public health interventions to mitigate air pollution should also target areas with intermediate levels of pollution. Citation Format: Anna L. Fischer, Guoli Zhou, Kelly A. Hirko. Associations between county-level air pollutants and early-onset breast cancer incidence rates in the U.S [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr B011.

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