To Identify Primary Resistance to CDK4/6 Inhibitors in Breast Cancer

This study tries to identify why some women with metastatic breast cancer do not respond to CDK4/6 inhibitor drugs (like palbociclib, ribociclib, or abemaciclib) — drugs that are often used as first-line treatment for hormone receptor-positive, HER2-negative metastatic breast cancer. **You may be eligible if...** - You are a woman 18 or older with hormone receptor-positive (ER+), HER2-negative metastatic breast cancer - You have not received prior treatment for metastatic breast cancer - You are about to start a CDK4/6 inhibitor combined with an aromatase inhibitor as your first-line treatment - You have evaluable disease on imaging and can provide a tumor tissue biopsy **You may NOT be eligible if...** - Your cancer has spread only to the brain with no other sites involved - You have had a different cancer (other than early-stage cervical or skin cancer) in the past 5 years Talk to your doctor to see if this trial is right for you.