This study is comparing palazestrant (OP-1250) with standard treatments for advanced breast cancer that is positive for estrogen receptors (ER+) and negative for human epidermal growth factor receptor 2 (HER2-). The trial is for adults whose cancer has worsened after using an endocrine therapy combined with a CDK4/6 inhibitor, which are drugs that help stop cancer cell growth. The trial aims to see if palazestrant is safer and more effective compared to standard treatments like fulvestrant or aromatase inhibitors (e.g., anastrozole, letrozole, exemestane), which help reduce estrogen levels or block its effects. About 510 participants will be involved. Eligible participants must have previously taken a CDK4/6 inhibitor, have certain health criteria, and not have received chemotherapy for advanced cancer.

• This is a large international trial with many participants.
• Participants will receive either palazestrant or standard treatment.
• The study is open-label, meaning both doctors and patients know what treatment is given.