This clinical trial is studying a treatment for HER2-positive, estrogen receptor-positive locally-advanced or metastatic breast cancer that has not been previously treated. HER2-positive means the cancer cells have higher than normal levels of a protein called human epidermal growth factor receptor 2, which promotes cancer cell growth. Estrogen receptor-positive means the cancer cells grow in response to the hormone estrogen. Locally-advanced cancer has spread to nearby tissues or lymph nodes, while metastatic cancer has spread to distant parts of the body. The study will use several medications including Phesgo, which is a combination of pertuzumab and trastuzumab given as an injection under the skin, RO7197597 (also called giredestrant) given as a capsule by mouth, and chemotherapy drugs called paclitaxel or docetaxel given through infusion into a vein. Additional medications may include hormone therapies such as letrozole, anastrozole, exemestane, or tamoxifen, and gonadotropin releasing hormone analogues.

The purpose of this study is to compare the effectiveness and safety of giredestrant combined with Phesgo versus Phesgo alone. The study will first give all participants an induction treatment phase consisting of Phesgo combined with a taxane chemotherapy. After this initial treatment phase, participants will be randomly assigned to receive either Phesgo combined with giredestrant or Phesgo alone. The study will measure how long participants live without their cancer getting worse, as well as overall survival time, how well the cancer responds to treatment, and the duration of that response.

During the study, participants will be monitored for side effects and changes in their health status. The study will also assess quality of life and how well participants are able to function in their daily activities using standardized questionnaires. Blood tests and other clinical assessments will be performed regularly to monitor safety throughout the treatment period.