This study tests how well a new treatment works for advanced breast cancer. The treatment combines inavolisib, a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i), and letrozole. These drugs will be compared with a placebo (sugar pill) plus CDK4/6i and letrozole. The study includes people with a specific type of breast cancer called "endocrine-sensitive PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer." This means the cancer grows with hormones, has a certain gene change (PIK3CA), and does not have too much of a protein called HER2.

• *The study will check how safe and effective this combination is.*
• *Participants must not have certain health issues like diabetes needing treatment or active lung disease.*
• *You must provide a sample of your tumor tissue.*

Participants will be closely monitored for changes in their health and how their cancer responds. Before joining, consider your health conditions and your ability to visit the study site regularly. Always talk to your doctor before joining a study.