BACKGROUND: Although the genetic and hormonal risk factors of breast cancer are well identified, they cannot fully explain the occurrence of all cases. Epidemiological and experimental studies have suggested that exposure to environmental pollutants, especially those with potential estrogenic properties, as polychlorinated biphenyls (PCBs) may have a role in breast cancer development. Being the most abundantly detected in human tissues and in the environment, congener 153 (PCB153) is widely used in epidemiological studies as indicator for total PCBs exposure. OBJECTIVES: We aimed to estimate the association between cumulative atmospheric exposure to PCB153 and breast cancer risk. METHODS: We conducted a case-control study of 5,222 cases and 5,222 matched controls nested within the French E3N cohort from 1990 to 2011. Annual atmospheric PCB153 concentrations were simulated with the deterministic chemistry-transport model (CHIMERE) and were assigned to women using their geocoded residential history. Their cumulative PCB153 exposure was calculated for each woman from their cohort inclusion to their index date. Breast cancer odds ratios (ORs) associated with cumulative PCB153 exposure and their 95% confidence intervals (95% CI) were estimated using multivariate conditional logistic regression models. RESULTS: Overall, our results showed a statistically significant linear increase in breast cancer risk related to cumulative atmospheric exposure to PCB153 as a continuous variable (adjusted OR=1.19; 95% CI: 1.08-1.31 for an increment of one standard deviation among controls (55 pg/m(3))). Among women who became postmenopausal during follow-up, the association remained statistically significant (adjusted OR=1.23; 95% CI: 1.09-1.39). In analyses by hormone receptors status, the positive association remained significant only for ER-positive breast cancer (adjusted OR=1.18; 95% CI: 1.05-1.33). DISCUSSION: This study is the first to have estimated the impact of atmospheric exposure to PCB153 on breast cancer risk. Our results showed a statistically significant increase in breast cancer risk, which may be limited to ER-positive breast cancer. These results warrant confirmation in further independent studies but raise the possibility that exposure to PCB153 increase breast cancer risk.Read less <