Inclusion Criteria:

• Individuals at least 18 years of age.
• Proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent.
• Documentation of histologically confirmed diagnosis of estrogen receptor positive (ER+) /HER2- breast cancer based on local laboratory results.
• Currently on AI (letrozole or anastrozole) + CDK4/6 inhibitor (palbociclib or abemaciclib) ± LHRH as the initial endocrine based treatment for advanced disease.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• ESR1m positive detected by central testing of ctDNA.
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Adequate organ and marrow function.

Exclusion Criteria:

• Individuals < 18 years of age.
• Advanced, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term.
• Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease.
• Any evidence of severe or uncontrolled systemic diseases which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
• Patient with known or family history of severe heart disease.
• Previous treatment with AZD9833, investigational SERDs or fulvestrant.
• Currently pregnant (confirmed with positive pregnancy test) or breastfeeding.
• Persistent non-haematological toxicities (CTCAE Grade > 2) caused by CDK4/6 inhibitor and/or AI treatment.

Eligibility last updated 8/16/21. Questions regarding updates should be directed to the study team contact.