ESR1 and neoplasm: Hosford et al. (2019) confirmed the involvement of the UPR and apoptosis in patient-derived estrogen-deprived estrogen receptor (ER)-positive xenografts treated with 17β‐estradiol (E2). This UPR and apoptosis–paired biology underpinning estrogen-induced tumor regression not only explains the earlier observational clinical science (Haddow, 1970) but also reaffirms estrogen’s therapeutic potential for the treatment of endocrine-resistant BC.