Air pollution and breast cancer incidence in a United States-wide prospective cohort study: Examining sensitive periods of exposure

Background

Mounting evidence supports that air pollution is related to a higher breast cancer risk, yet the importance of exposure timing in this relationship remains unclear.

Methods

In the Sister Study, a United States-wide prospective cohort (n = 50,884, 2003–2009), we estimated time-varying annual concentrations of nitrogen dioxide (NO2) and fine particulate matter (PM2.5) from 1990 to 2017 at residential addresses using validated spatiotemporal models. Self-reported breast cancer diagnoses were validated using medical records. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for breast cancer incidence in relation to air pollutant concentrations during predetermined windows of susceptibility. We also applied distributed lag non-linear models to estimate adjusted cumulative and lag-specific HRs and 95 % CIs for the association between air pollutants and breast cancer across a lag period of 0–15 years. We evaluated breast cancer overall and by estrogen receptor (ER) status and tumor extent [ductal carcinoma in situ (DCIS) versus invasive].

Results

We found limited evidence that air pollutant exposure during the time of a woman’s first birth, most recent birth, or menopause transition was associated with heightened risk for breast cancer. When examining exposure flexibly over the long-term, a 10-ppb increase in NO2 across lag years 1–11 significantly contributed to the risk of ER-positive (HRcumul = 1.14; 95 % CI: 1.03–1.27; n = 2619 cases) and DCIS (HRcumul = 1.27, 95 % CI: 1.04–1.54; n = 706 cases) breast cancer, whereas PM2.5 experienced during lag years 11–13 was associated with ER-negative breast cancer (e.g., HRLag12 = 1.36 per 10-µg/m3 increase, 95 % CI: 1.02–1.81; n = 448 cases).

Conclusions

We identified unique periods of susceptibility to NO2 and PM2.5 for breast cancer risk by ER status.