Background
Breast cancer etiology is multifactorial, and environmental exposures are increasingly suspected to contribute to risk. Growing epidemiological evidence suggests that ambient air pollution—particularly fine and coarse particulate matter (PM?.?, PM??) and nitrogen dioxide (NO?)—may play a role in breast carcinogenesis. However, associations reported for particulate matter remain heterogeneous, while findings for NO? appear more consistent, especially in urban settings. Most previous studies have relied on single-year or long-term average exposure metrics, which may obscure temporal variability and sustained exposure patterns.

Objectives 
This study aimed to identify long-term residential exposure trajectories to PM?.?, PM??, and NO? using latent class mixed models (LCMM) and to evaluate their associations with breast cancer risk.

Methods
We used data from the XENAIR case–control study nested within the French E3N-Generations cohort (98,995 women aged 40–65 years at inclusion, 1990–1991). Incident breast cancer cases diagnosed between 1990 and 2011 were individually matched to controls. Annual outdoor concentrations of PM?.?, PM??, and NO? (µg/m³) were estimated at each residential address from cohort entry to diagnosis (or matched index date) using national-scale Land Use Regression models. Pollutant-specific exposure trajectories were identified using LCMM. Associations between trajectory class membership and breast cancer were estimated using conditional logistic regression, accounting for matching factors, classification uncertainty, and multiple imputation for missing covariates. Additional analyses were stratified by menopausal status and hormone receptor subtype.

Results
The study included 5,056 breast cancer cases and 5,057 matched controls. Four distinct exposure trajectories were identified for PM?.? and PM??, and three for NO?. Women assigned to the highest PM?.? trajectory, characterized by persistently elevated concentrations over follow-up (Class 4, 8.8%; median 37.0 µg/m³), had higher odds of breast cancer compared with those in the lowest exposure trajectory (OR = 1.22; 95% CI: 1.02–1.47). No statistically significant associations were observed for PM?? or NO? trajectories in the main analyses. High-exposure trajectories for all pollutants were strongly clustered in major metropolitan areas, reflecting a marked urban–rural exposure gradient.

Conclusion
These findings suggest that long-term exposure to elevated PM?.?, particularly sustained high exposure over time, may contribute to increased breast cancer risk. Exposure trajectories were strongly shaped by geographic context, with the highest long-term exposure profiles predominantly observed in urban and metropolitan areas. Together, these results highlight the importance of considering spatially structured, long-term exposure patterns when investigating breast cancer risk and reinforce persistent urban exposure to fine particulate matter as a key public health concern.
 

Graphical abstract_TrajAirPoll&BreastCancer_BlandineLeProvost