Liquid-biopsy Informed Platform Trial to Evaluate CDK4/6-inhibitor Resistant ER+/HER2- Metastatic Breast Cancer

Inclusion Criteria: * Patients must have histologically and/or cytologically confirmed, advanced / metastatic breast cancer, ER \>10% and not HER2 overexpressing/amplified as per ASCO/CAP criteria. Patients with locally advanced or inflammatory disease without distant metastases that is potentially resectable or treatable with curative intent are not eligible * All patients must have a formalin fixed paraffin embedded tissue block (from primary or metastatic tumour) available and must have provided informed consent for the release of the block * Patients must have had objective disease progression demonstrated on (defined as while taking or within 8 weeks of the last dose) first line CDK4/6i + ET for MBC. Patients who discontinued CDK4/6i + ET without disease progression more than 8 weeks prior to objective disease progression (toxicity, patient request) are not eligible. Patients must have received at least 24 weeks of first line CDK4/6i + ET therapy * Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 21 days prior to enrollment (within 28 days if negative). All patients must have measurable disease as defined by RECIST 1.1. * The criteria for defining measurable disease are as follows: * Chest x-ray ≥ 20 mm * CT scan (with slice thickness of 5 mm) ≥ 10 mm: longest diameter * Physical exam (using calipers) ≥ 10 mm * Lymph nodes by CT scan ≥ 15 mm: measured in short axis * Patients must be ≥ 18 years of a…