Minimally Interventional Study on Prevalence of Emerging ESR1 Mutations in Liquid Biopsy in Three Cohorts of Patients With Breast Cancer in Comparison With Patient's Baseline ESR1 Mutation Status as Defined by Tissue Profiling.

This study is tracking genetic mutations that develop in hormone receptor-positive (HR+), HER2-negative metastatic breast cancer as it is treated, particularly using blood tests (liquid biopsies) to detect these changes over time. Understanding these mutations may help doctors make better treatment decisions. **You may be eligible if...** - You are 18 or older (any gender) - You have advanced or metastatic breast cancer that is hormone receptor-positive (HR+) and HER2-negative - You are a candidate for CDK4/6 inhibitor therapy combined with hormone therapy as a first-line treatment, OR your cancer has already progressed on CDK4/6 inhibitor therapy - You are willing to undergo a blood test (liquid biopsy) before starting or changing treatment - You have signed an informed consent form **You may NOT be eligible if...** - Your cancer is HER2-positive - You have already received hormone therapy for your metastatic disease (prior chemotherapy in metastatic setting is allowed with limits) - You are unwilling to have a liquid biopsy Talk to your doctor to see if this trial is right for you.