Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis was applied on a series of 54 2-arylbenzothiophene derivatives, synthesized by Grese and coworkers, based on raloxifene (an estrogen receptor-alpha antagonist), and evaluated as ERα ligands and as inhibitors of estrogen-stimulated proliferation of MCF-7 breast cancer cells. This evidence concerns the gene ESR1 and breast cancer.