To delineate the direct contribution of mitochondrial ER-α and ER-β in endocrine therapy response and mitochondrial priming in breast cancer cells, we depleted ER-β in ER-α (−) HC1187, HCC1569, MDA-MB-436, and BT-20 cells by using shRNA-mediated silencing. The gene discussed is ESR2; the disease is breast carcinoma.