STUDY02001740;22SCH740: Estradiol For ER+ Advanced Breast Cancer (ESTHER)

Determine whether subjects harboring ESR1-mutant/amplified breast cancer have a higher rate of clinical benefit from 17b-estradiol therapy than subjects with ESR1-wild-type breast cancer

Inclusion Criteria:Post-menopausal women with ER+ breast cancer.Metastatic or locoregional recurrence not amenable to treatment with curativeintent.Received ≥1 prior line of endocrine-based therapy (e.g., including tamoxifen, aromatase inhibitors, fulvestrant, or combinations) in the advanced/metastatic settingExclusion Criteria:During the study Treatment Phase with 17b-estradiol, no concurrent anti-cancer therapies are allowed with the following exceptions:Exception: Trastuzumab is allowed for the treatment of subjects with a history of HER2+ disease, and will be used at the physician's discretion.Exception: Anti-resorptive bone therapies (e.g., bisphosphonates, denosumab) are permitted.Any investigational cancer therapy in the last 3 weeks.Known CNS disease, unless clinically stable for ≥ 3 months.History of any of the following:Deep venous thrombosis.Pulmonary embolism.Stroke.Acute myocardial infarction.Congestive heart failure.Previous malignancy not treated with curative intent, or with an estimated recurrence risk ≥30%.