Additional Baseline Characteristics and Their Relevance to Clinical Practice

Stratification in clinical trials, such as by ESR1 mutation status, presence of visceral metastases, and prior fulvestrant exposure, mirrors key considerations in real-world management of ER+/HER2- metastatic breast cancer. ESR1 mutations are critical drivers of endocrine resistance, making their identification essential for selecting effective therapies and predicting response. Visceral metastases are associated with more aggressive disease and often prompt earlier use of potent endocrine or cytotoxic therapies. Prior fulvestrant exposure informs sequencing decisions, as resistance mechanisms may influence the efficacy of subsequent endocrine options, including newer oral SERDs. In clinical practice, these factors guide personalized treatment strategies, balancing efficacy, safety, and patient quality of life.