Environmental exposure to cadmium in breast cancer - association with the Warburg effect and sensitivity to tamoxifen

Abstract

The association between cadmium and breast cancer remains unexplained due to inconsistent epidemiological data and unknown underlying mechanisms. This study aimed to assess the relationship between environmental exposure to cadmium and the Warburg effect in breast cancer and, thus, its possible interference with breast cancer treatment. The observational study in two groups of breast cancer patients indicated a positive correlation between urinary cadmium concentration and tumor expression of HIF1A (a master regulator of the Warburg effect). Further explanatory research in MCF-7 cells showed no impact of cadmium exposure on molecular and biochemical markers of the Warburg effect. However, long-term exposure to a low and environmentally relevant concentration of cadmium led to the accumulation of the metal in MCF-7 cells and decreased their sensitivity to tamoxifen. To conclude, the association between cadmium and the Warburg effect was suggested in the observational study, although not confirmed in vitro. Nevertheless, cadmium seems to interfere with tamoxifen treatment which deserves further investigation in terms of its possible implication in intrinsic resistance to hormone therapy.

Keywords: Breast cancer; Cadmium; HIF1A; Tamoxifen; Warburg effect.