Dietary cadmium and risk of breast cancer subtypes defined by hormone receptor status: A prospective cohort study

Diet is the primary source of cadmium—a proven Group 1 human carcinogen—for non‐smokers. Observational studies investigating the effect of cadmium from food sources on breast cancer risk have produced inconsistent results. We examined the association between dietary cadmium and risk of breast cancer defined by estrogen receptor (ER), progesterone receptor (PR) and HER2 status, in 8924 women recruited to a prospective study between 1987 and 1992. Dietary cadmium intake was estimated using a semi‐quantitative food frequency questionnaire at baseline. During a median of 22 years of follow‐up, 451 incident cases of breast cancer were identified through the Varese Cancer Registry. Multivariable‐adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for breast cancer and receptor‐defined breast cancer subtypes were estimated for quintiles of dietary cadmium intake, adjusting for confounding factors. Mean dietary cadmium intake was 7.8 (standard deviation 1.4) μg/day. Women with highest quintile of cadmium intake had a greater risk of breast cancer (HR 1.54; 95% CI, 1.06–2.22; p trend = 0.028) than those with lowest quintile of intake. Women premenopausal at recruitment had HR = 1.73 (95% CI, 1.10–2.71, highest vs. lowest quintile); postmenopausal women had HR = 1.32 (95% CI, 1.05–1.66 for each standard deviation increase in cadmium). Cadmium‐related risk of breast cancer did not vary with ER, PR or HER2 status (p‐heterogeneity not significant). These findings support the hypothesis that dietary cadmium is a risk factor for breast cancer. What's new? Diet is the primary source of cadmium – a proven Group 1 human carcinogen – for non‐smokers. Observational studies investigating the effect of cadmium from food sources on breast cancer risk have produced inconsistent results, however. This first cohort study to investigate the effects of dietary cadmium on the risk of breast cancer and breast cancer subtypes defined by the expression of ER, PR, and HER2 provides further evidence that dietary cadmium increases breast cancer risk. The lack of significant heterogeneity in risk estimates between different ER and PR status neither supports nor refutes the hypothesis that cadmium acts as a metalloestrogen.