A CDK4/6 inhibitor different from the first that the participant had received, plus fulvestrant.

The goal of this clinical trial is to learn if an artificial intelligence model will be able to select patients with advanced breast cancer who may respond to a second cyclin-dependent kinase 4/6 (CDK4/6) inhibitor after they have progressed on the first CDK4/6 inhibitor. Patients for this study need to have hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. The main questions the study aims to answer are: If the artificial intelligence model says that a patient's tumor should respond to the second CDK4/6 inhibitor, and that patient receives the second CDK4/6 inhibitor together with fulvestrant (an endocrine therapy also called Faslodex), will it take longer for the tumor to get worse than if the patient receives another type of therapy? Will the tumor respond better? Will the therapy be safe? Researchers will compare the combination of a second CDK4/6 inhibitor plus fulvestrant to the therapy chosen by the physician. Participants will: Take the assigned therapy based on the way the therapy is usually prescribed. Visit the clinic once every month for checkups, tests, and questionnaires. Keep a diary of the pills they take at home.