Cadmium exposure and risk of breast cancer by subtype

Abstract

There is evidence that cadmium (Cd) may be a risk factor for breast cancer. We examined the association between Cd and breast cancer subtypes by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status. A hospital-based case-control study was performed in 585 cases and 1170 controls. Information on possible risk factors was collected via a questionnaire. Urinary Cd was determined by atomic absorption spectrometry. The ER, PR and HER2 levels in tumor tissue were analyzed by immunohistochemistry. Logistic regression was used for analyses. All statistical tests were 2-sided. After adjustment for age and other confounders, the odds ratio (OR) of breast cancer was 1.31 (95% confidence intervals (CI): 1.01-1.7) in women with urinary Cd 0.176- 0.33 µg/g creatinine and 1.57 (95% CI: 1.21-2.04) in women having ≥0.331 µg Cd/g creatinine, both compared with women having Cd <0.176 µg/g creatinine. The association of Cd with hormone receptor-positive breast cancer seemed to be stronger than with hormone receptor-negative: the OR of ER+ and ER- breast cancer per 1 category increase was 1.33 (95% CI: 1.15-1.56) and 1.13 (95% CI: 0.92-1.38); the OR of PR+ and PR- cancer per 1 category increase was 1.37 (95% CI: 1.15-1.64) and 1.17 (95% CI: 0.99-1.37); the OR of ER+/PR+ and ER-/PR- cancer per 1 category increase was 1.38 (95% CI: 1.15-1.66) and 1.12 (95% CI: 0.91-1.38). However, heterogeneity in the associations between Cd and either receptor-positive or receptor-negative breast cancer was not significant (P=0.132-0.186). The strongest association with Cd was found in ER+/PR+/HER2- cases with suggestive heterogeneity in the association between Cd and either ER+/PR+/HER2- or ER-/PR-/HER2+ breast cancer (P=0.065). The study provides evidence that the association between cadmium and risk of breast cancer differs by tumor receptor status, with a stronger risk demonstrated in ER+/PR+/HER2- breast cancer.