Basedoxifene is related to a metabolite of a failed breast cancer drug zindoxifene [124] and arzoxifene is the end product in the line of 4-hydroxytamoxifen [35], the antiestrogen is a metabolite of tamoxifen with high affinity for the ER but poor antitumor activity [37], to raloxifene (also with a poor antitumor activity [125]) and then to arzoxifene in an attempt to improve pharmacokinetics and develop a better breast cancer drug. The gene discussed is ESR1; the disease is breast cancer.