Cadmium interferes with the antiproliferative effect of fulvestrant in endocrine therapy-resistant estrogen receptor α-positive breast cancer cells.

Fulvestrant (FUL), an estrogen receptor α (ERα)-degradative anti-estrogen, is used alone or in combination with cyclin-dependent kinase 4/6 inhibitors for the treatment of advanced ERα-positive breast cancer (BC) in postmenopausal women. Cadmium (Cd), an environmental pollutant and metalloestrogen, binds to ERα as a ligand. Patients with BC may experience disease progression despite FUL treatment, suggesting potential interactions between FUL and Cd in long-term estrogen-deprived (LTED) cells. Therefore, the effect of FUL and Cd interaction in LTED cells, a model of postmenopausal BC, was investigated. LTED cells were treated with FUL and Cd at therapeutically or physiologically relevant concentrations, both simultaneously and sequentially (either with FUL treatment followed by Cd or Cd pre-treatment followed by FUL). FUL treatment alone decreased LTED cell viability; however, Cd pre/post-treatment attenuated the antiproliferative effect of FUL. Western blotting showed that Cd pre/post-treatment did not affect FUL-induced ERα degradation. Hence, Cd could suppress the antiproliferative effect of FUL in LTED cells.