Resistance to antiestrogen therapy is one of the major barriers to the successful treatment of breast cancer, and ER-α expression is currently the main biomarker of response to antiestrogen treatment.5, 6, 9, 40, 41 It has been well established that a combination of genetic, epigenetic, and transcriptional controls regulates ER-α expression. The gene discussed is ESR1; the disease is breast carcinoma.