Before joining the study, people will have health tests such as physical exams, blood and urine tests, heart tests, scans, and testing of their tumor to see if they can participate.

If they qualify, they will be placed into a treatment group by chance. One group will receive a new study medicine called BGB 43395 together with a medicine called letrozole. Other groups will receive approved breast cancer medicines called abemaciclib, palbociclib, or ribociclib together with letrozole. All of the study medicines are taken by mouth.

During the study, participants will have regular clinic visits, blood tests, heart monitoring, imaging scans, questionnaires, and keep a daily record of their medicines. The study may last for several years, and doctors will continue to check on participants even after the study treatment ends.

This study is for adults who have a type of breast cancer called HR positive, HER2 negative breast cancer. The cancer has spread from the breast to other parts of the body. People in the study have not received treatment before for breast cancer that has spread. Researchers are studying new ways to treat this type of cancer and improve care for patients with advanced disease.

People may be able to join this study if they are 18 years old or older and have a type of breast cancer called hormone receptor positive and HER2 negative breast cancer that has spread beyond the breast. They must not have received medicine treatment before for advanced or metastatic breast cancer. They must also have at least one tumor that can be measured on scans such as CT or MRI.

People cannot join if they have untreated cancer that has spread to the brain or the lining around the brain and spinal cord. They also cannot have serious heart problems or other major health conditions that could make taking part in the study unsafe.

This study is testing a new medicine called BGB 43395 for people with a type of breast cancer that is HR positive and HER2 negative and has spread beyond the breast. Researchers want to learn if BGB 43395 is safe and how well it works when combined with a medicine called letrozole.

The study will compare BGB 43395 with other approved breast cancer medicines that are already used with letrozole. These medicines are called abemaciclib, palbociclib, and ribociclib. Researchers want to see which treatment works best as the first medicine treatment for advanced breast cancer. The goal is to find better treatment options for people with this type of cancer in the future.