The research question addressed in the present study, therefore, was whether ER-regulated genes associated with an anti-proliferative function were silenced by promoter methylation in tamoxifen-resistant breast cancer cells as a consequence of prolonged tamoxifen treatment; and whether re-activation of such genes could induce an anti-proliferative response and thus provide a potential therapeutic avenue for the management of tamoxifen-resistant disease. This evidence concerns the gene ESR1 and breast carcinoma.