Long-term airborne dioxin exposure and breast cancer risk in a case-control study nested within the French E3N prospective cohort

Cadmium, due to its estrogen‐like activity, has been suspected to increase the risk of breast cancer; however, epidemiological studies have reported inconsistent findings. We conducted a case–control study (4,059 cases and 4,059 matched controls) nested within the E3N French cohort study to estimate the risk of breast cancer associated with long‐term exposure to airborne cadmium pollution, and its effect according to molecular subtype of breast cancer (estrogen receptor negative/positive [ER−/ER+] and progesterone receptor negative/positive [PR−/PR+]). Atmospheric exposure to cadmium was assessed using a Geographic Information System‐based metric, which included subject's residence‐to‐cadmium source distance, wind direction, exposure duration and stack height. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Overall, there was no significant association between cumulative dose of airborne cadmium exposure and the risk of overall, premenopausal and postmenopausal breast cancer. However, by ER and PR status, inverse associations were observed for ER− (OR Q5 vs . Q1 = 0.63; 95% CI: 0.41–0.95, p trend = 0.043) and for ER−/PR− breast tumors (OR Q4 vs . Q1 = 0.62; 95% CI: 0.40–0.95, OR Q5 vs . Q1 = 0.68; 95% CI: 0.42–1.07, p trend = 0.088). Our study provides no evidence of an association between exposure to cadmium and risk of breast cancer overall but suggests that cadmium might be related to a decreased risk of ER− and ER−/PR− breast tumors. These observations and other possible effects linked to hormone receptor status warrant further investigations.