Non-occupational exposure to cadmium and breast cancer: A comprehensive and critical review

Breast cancer (BC) is a multifactorial disease with unresolved etiology. Environmental pollutants, primarily trace metals, play a pivotal role in the pathophysiological cascade of malignant tumors, including BC. In this up-to-date review, we comprehensively and critically examined the relationship between cadmium (Cd) and BC. For this purpose, peer-reviewed studies from relevant databases (PubMed, SCOPUS, and Cochrane Library) over the last 40 years were retrieved and analyzed. We found that in vitro and in vivo studies strongly support the view that Cd has harmful effects on breast health. According to the human studies, we found that Cd could be responsible for the development and progression of malignant breast tumors due to markedly higher levels in clinical matrices of cases (whole blood, urine, breast tissue, keratin materials) than in clinical matrices of controls. Cadmium does not appear to affect BC density. In contrast, Cd has been found to have a detrimental effect on sex hormones, disrupting the balance of estrogen and androgen. We found that studies looking at dietary Cd intake and BC risk generally (without measuring urine or blood Cd) do not support the association between dietary Cd intake and BC risk. In notable contrast, studies looking at dietary Cd intake and BC risk by measuring Cd in urine or blood generally support this association. The effect of airborne Cd on BC risk was weak, but in favor of specific histological forms, primarily ER-/PR- invasive tubular breast carcinomas. Regardless of the intake route of Cd into the body, it can be concluded that Cd has a harmful effect on breast health. However, well-designed longitudinal, mechanistic, meta-analytic, and other studies are urgently needed to confirm the exact role of environmental Cd in breast carcinogenesis.