Metals and Breast Cancer Risk: A Prospective Study Using Toenail Biomarkers

The role of metals in breast cancer is of interest because of their carcinogenic and endocrine disrupting capabilities. Evidence from epidemiologic studies remains elusive and prior studies have not investigated metal mixtures. In a case-cohort nested within the Sister Study cohort (enrolled 2003-2009; followed through September 2017), we measured 15 metals in toenails collected at enrollment in a race-stratified sample of 1495 cases and a sub-cohort of 1605 women. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for each metal using Cox regression and robust variance. We used quantile g-computation to estimate the joint association between multiple metals and breast cancer risk. Average follow-up was 7.5 years. There was little evidence supporting an association for individual metals and breast cancer. An exception was molybdenum, which was associated with reduced incidence of overall breast cancer risk (3rd vs. 1st tertile HR=0.82 (95% CI: 0.67, 1.00)). An inverse association for antimony was observed among non-Hispanic Black women. Pre-defined groups of metals (all, non-essential, essential, and metalloestrogens) were not strongly associated with breast cancer. This study offers little support for metals individually or as mixtures as risk factors for breast cancer. Mechanisms for inverse associations with some metals warrant further study.