Abstract PS4-09-28: Air Pollution and Oncotype DX recurrence socre: implications for racial disparities in breast cancer

Abstract Background Nearly 70% of breast cancer patients are diagnosed with estrogen receptor (ER) positive, human epidermal growth factor-2 (HER2) negative breast cancer—a subtype with generally more favorable survival. Precision medicine for this subtype has been informed by gene expression assays, such as the Oncotype DX (ODX) recurrence score, that assess the 10-year risk of distant recurrence (Low, Medium, or High) and guide treatment decisions. Air pollution is recognized has been linked to more aggressive breast cancer subtypes, suggesting that exposure to air pollution may contribute to more aggressive tumors. However, no study has examined air pollution in relation to ODX, which can be used as a marker of tumor aggressiveness. We evaluated the associations of two air pollutants (PM2.5 and NO2) with ODX recurrence score among Black and White breast cancer patients. Methods We identified all women aged ≥18 years, diagnosed with a stage I-III first primary breast cancer between 2010 and 2015 in the Georgia Cancer Registry. Breast cancer patients were included if they were non-Hispanic Black (NHB) or non-Hispanic White (NHW) and had an ODX recurrence score. Daily ambient PM2.5 and NO2 concentrations were predicted at a 1-km resolution for the years 2005-2010 using an ensemble of three machine learning models available from the Environmental Protection Agency. For each patient, we assigned PM2.5 and NO2 exposures based on the average value in the 5-years prior to their diagnosis. We used multinomial regression to estimate the associations between a 5-unit increase in PM2.5 and NO2 and higher ODX scores (Intermediate vs Low and High vs Low), overall and by race. Models were adjusted for age at diagnosis (years), race (overall model only), and rurality. Results In the Georgia cohort (77% NHW, 23% NHB), 6985 women received ODX testing—4090 (56%) were classified as Low, 2394 (34%) as Intermediate, and 501 (7.2%) as High risk. A larger proportion of those with a High ODX recurrence score were NHB (30%) compared with a Low recurrence score (21%). In the overall study population, a 5-unit increase in PM2.5 was associated with higher odds of both an Intermediate (odds ratio [OR]=1.20, 95%CI: 1.02, 1.41) and High (OR=1.31, 95%CI: 0.97, 1.76) recurrence score compared with those in the Low-risk group (Table 1). Among NHW patients, these associations were attenuated (Intermediate vs Low: OR=1.14, 95%CI: 0.95, 1.36; High vs Low: OR=1.23, 95%CI: 0.87, 1.75). However, among NHB women, the associations were more pronounced (Intermediate vs Low: OR=1.48, 95%CI: 1.05, 2.09; High vs Low: OR=1.56, 95%CI: 0.88, 2.76). We did not observe associations between NO2 and ODX groups. Conclusions Our preliminary results suggest that air pollution, particularly PM2.5, may influence tumor aggressiveness. Moreover, this association may differentially impact NHB breast cancer patients, who are also more likely to live in areas with higher air pollution. Citation Format: L. J. Collin, T. Armide, L. E. Barber, K. Bishop, C. M. Destin, M. L. Maliniak, J. M. Switchenko, L. E. McCullough. Air Pollution and Oncotype DX recurrence socre: implications for racial disparities in breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-09-28.