This study looks at two different treatments for a type of breast cancer called HR+/HER2-. HR+ means the cancer grows with hormones. HER2- means it doesn’t have too much of a certain protein. One treatment uses a new drug called BGB-43395 combined with letrozole, a medicine that stops the body from making estrogen, a hormone that can help cancer grow. The other treatment uses a CDK4/6 inhibitor (CDK4/6i), a drug that stops cancer cells from growing, also with letrozole.

• Participants must be 18+ years old and have not had treatment for advanced breast cancer before.
• This study checks how well the treatments work and their safety.
• Participants must have good overall health and organ function.

Note: You can’t join if you've had treatment for advanced cancer before or have certain types of brain problems. This study is for people who want to try a new treatment. Talk to your doctor to see if it’s right for you!