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

This study uses liquid biopsy (a blood test that detects circulating tumor DNA) to guide treatment decisions for people with advanced breast cancer that is hormone receptor positive (ER+) and HER2 negative, and whose cancer has stopped responding to CDK4/6 inhibitors (a common type of targeted therapy). The study assigns different treatments based on the specific genetic changes found in the blood test. **You may be eligible if...** - You have confirmed advanced or metastatic ER-positive, HER2-negative breast cancer - Your cancer has progressed on a CDK4/6 inhibitor (such as palbociclib, ribociclib, or abemaciclib) - You are willing to provide blood samples for liquid biopsy testing - Your organ function meets required levels **You may NOT be eligible if...** - Your breast cancer is HER2-positive or ER-negative - You have not previously received a CDK4/6 inhibitor - You have untreated brain metastases - You have serious health conditions that would make the study treatments unsafe Talk to your doctor to see if this trial is right for you.