This study aims to investigate the molecular mechanisms of tamoxifen resistance in ERα-positive breast cancer, with particular focus on the role of SET Domain Containing 1A (SETD1A)-driven forkhead box A2 (FOXA2) as a key regulator of this resistance.<h4>Methods</h4>FOXA2 expression and its regulation by SETD1A were assessed via (quantitative polymerase chain reaction), western blotting, transcriptome profiling, and chromatin immunoprecipitation analyses. The gene discussed is ESR1; the disease is breast cancer.