This included drug treatments that interrogate ER-mediated and translation-independent regulation, integration of additional in vitro estrogen-response data and human breast tumor sample gene-expression data for candidate gene validation and identification of relevant in vivo targets, computational binding site modeling and promoter analysis to map putative ER-binding sites, and chromatin immunoprecipitation (ChIP) to characterize the interaction between ER and the regulatory elements of candidate target genes. This evidence concerns the gene ESR1 and breast neoplasm.