Hormonal manipulation is achieved either at a cellular level by using anti-estrogens, such as tamoxifen, to compete for ER in the breast tumor, or systemically, by lowering estrogen levels in premenopausal women by the use of luteinizing hormone-releasing hormone agonists and in postmenopausal women by aromatase inhibitors that block estrogen biosynthesis in non-ovarian tissues. Here, ESR1 is linked to breast neoplasm.