Benzo[a]pyrene (BaP) is an endocrine-disrupting pollutant formed during incomplete combustion of organic materials. It has been recognized as a reproductive and developmental toxicant, however epidemiological evidence of the long-term effect of ambient air BaP on breast cancer (BC) is limited. Thus we evaluated associations between ambient air BaP exposure and risk of BC, overall and according to menopausal status and molecular subtypes (estrogen receptor negative/positive (ER-/ER+) and progesterone receptor negative/positive (PR-/PR+)), stage and grade of differentiation of BC in the French E3N cohort study. Within a nested case-control study of 5222 incident BC cases and 5222 matched controls, annual BaP exposure was estimated using a chemistry-transport model (CHIMERE) and was assigned to the geocoded residential addresses of participants for each year during the 1990-2011 follow-up period. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Overall, cumulative airborne BaP exposure was significantly associated with the overall risk of BC, for each 1 interquartile range (IQR) increase in the concentration levels of BaP (1.42 ng/m3), the OR = 1.15 (95% CI: 1.04-1.27). However, by menopausal status, the significant positive association remained only in women who underwent menopausal transition (i.e. premenopausal women at inclusion who became postmenopausal at diagnosis), OR per 1 IQR = 1.20 (95% CI: 1.03-1.40). By hormone receptor status, positive associations were observed for ER+, PR + and ER + PR + BC, with ORs = 1.17 (95% CI: 1.04-1.32), 1.16 (95% CI: 1.01-1.33), and 1.17 (95% CI: 1.01-1.36) per 1 IQR, respectively. There was also a borderline positive association between BaP and grade 3 BC (OR per 1 IQR = 1.15 (95% CI: 0.99-1.34). We provide evidence of increased risk of BC associated with cumulative BaP exposure, which varied according to menopausal status, hormone receptor status, and grade of differentiation of BC. Our results add further epidemiological evidence to the previous experimental studies suggesting the adverse effects of BaP.

Current evidence of an association of breast cancer (BC) risk with air pollution exposure, in particular from traffic exhaust, remains inconclusive, and the exposure assessment methodologies are heterogeneous. This study aimed to conduct a systematic review and meta-analysis on the association between traffic-related air pollution (TRAP) and BC incidence (PROSPERO CRD42021286774). We systematically reviewed observational studies assessing exposure to TRAP and BC risk published until June 2022, available on Medline/PubMed and Web of Science databases. Studies using models for assessing exposure to traffic-related air pollutants or using exposure proxies (including traffic density, distance to road, etc.) were eligible for inclusion. A random-effects meta-analysis of studies investigating the association between NO₂/NO_x exposure and BC risk was conducted. Overall, 21 studies meeting the inclusion criteria were included (seven case–control, one nested case–control, 13 cohort studies); 13 studies (five case–control, eight cohort) provided data for inclusion in the meta-analyses. Individual studies provided little evidence of an association between TRAP and BC risk; exposure assessment methods and time periods of traffic emissions were different. The meta-estimate on NO₂ exposure indicated a positive association (pooled relative risk per 10 µg/m³ of NO₂: 1.015; 95% confidence interval, CI: 1.003; 1.028). No association between NO_x exposure and BC was found (three studies). Although there was limited evidence of an association for TRAP estimated with proxies, the meta-analysis showed a significant association between NO₂ exposure, a common TRAP pollutant marker, and BC risk, yet with a small effect size. Our findings provide additional support for air pollution carcinogenicity.

Dioxins, Group 1 carcinogens, are emitted by industrial chlorinated combustion processes and suspected to increase breast cancer risk through receptor-mediated pathways. We estimated breast cancer risk associated with airborne dioxin exposure, using geographic information system (GIS) methods and historical exposure data. We designed a case-control study (429 breast cancer cases diagnosed between 1990 and 2008, matched to 716 controls) nested within the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort. Airborne dioxin exposure was assessed using a GIS-based metric including participants' residential history, technical characteristics of 222 dioxin sources, residential proximity to dioxin sources, exposure duration and wind direction. Odds ratios (OR) and 95% confidence intervals (CI) associated with quintiles of cumulative exposure were estimated using multivariate logistic regression models. We observed no increased risk of breast cancer for higher dioxin exposure levels overall and according to hormone-receptor status. We however observed a statistically significant OR for Q2 versus Q1 overall (1.612, 95% CI: 1.042-2.493) and for estrogen-receptor (ER) positive breast cancer (1.843, 95% CI: 1.033-3.292). Overall, as well as according to hormone-receptor status, no increased risk was observed for higher airborne dioxin exposure. The increased risk for low exposure levels might be compatible with non-monotonic dose-response relationship. Confirmation of our findings is required. Our GIS-based metric may provide an alternative in absence of ambient dioxin monitoring and may allow assessing exposure to other pollutants.

Dioxins are environmental and persistent organic carcinogens with endocrine disrupting properties. A positive association with several cancers, including risk of breast cancer has been suggested. This study aimed to develop and assess performances of an exposure metric based on a Geographic Information System (GIS) through comparison with a validated dispersion model to estimate historical industrial dioxin exposure for its use in a case-control study nested within a prospective cohort. Industrial dioxin sources were inventoried over the whole French territory (n > 2500) and annual average releases were estimated between 1990 and 2008. In three selected areas (rural, urban and urban-costal), dioxin dispersion was modelled using SIRANE, an urban Gaussian model and exposure of the French E3N cohort participants was estimated. The GIS-based metric was developed, calibrated and compared to SIRANE results using a set of parameters (local meteorological data, characteristics of industrial sources, e.g. emission intensity and stack height), by calculating weighted kappa statistics (wκ) and coefficient of determination (R2). Furthermore, as performance evaluation, the final GIS-based metric was tested to assess atmospheric exposure to cadmium. The concordance between the GIS-based metric and the dispersion model for dioxin exposure estimate was strong (wκ median = 0.78 (1st quintile = 0.72, 3rd quintile =0.82) and R2 median = 0.82 (1st quintile = 0.71, 3rd quintile = 0.87)). We observed similar performance for cadmium. Our study demonstrated the ability of the GIS-based metric to reliably characterize long-term environmental dioxin and cadmium exposures as well as the pertinence of using dispersion modelling to construct and calibrate the GIS-based metric.