Exposure to airborne cadmium and breast cancer stage, grade and histology at diagnosis: findings from the E3N cohort study

Purpose Molecular and cellular studies reported a role of cadmium in risk of advanced breast cancer (BC). However epidemiological evidence is limited. Our previous study suggests that cadmium might be related to a decreased risk of ER- and ER-PR- breast tumors. In this study, we further explored the association between long-term exposure to airborne cadmium and risk of BC by stage, grade of differentiation, and histological types at diagnosis. Methods A nested case-control study of 4,401 cases and 4,401 matched controls was conducted within the French E3N cohort. A Geographic Information System (GIS) based metric was employed to evaluate outdoor airborne exposure to cadmium. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. Results There was no statistically significant association between cadmium exposure and stage of BC in the multivariable analyses. The adjusted ORs for the fifth versus first quintile were 1.02 (95% CI: 0.83–1.25), 1.11 (95% CI: 0.84–1.49), and 0.67 (95% CI: 0.37–1.24) for stages I, II, and III-IV BC, respectively. The subgroup analyses showed no statistically significant association between cadmium exposure and grade of differentiation of BC at diagnosis. However, further analyses by histological type suggested a positive dose-response association between cadmium and risk of invasive tubular carcinoma (ITC) BC (OR for the fifth versus first quintile = 3.44 (95% CI: 1.10–10.7)). Conclusions Our results do not support the hypothesis that airborne cadmium exposure may have a role in advanced BC risk, but suggest that cadmium may be associated with an increased risk of ITC. However, these results should be considered with caution, and more epidemiological studies are needed to confirm our findings and to improve our understanding of the effects of cadmium exposure according to several clinic-pathological characteristics of BC.