Examining Therapies Used in Later Lines of Treatment in ER+/HER2- Metastatic Breast Cancer

In ER+/HER2- metastatic breast cancer, treatment in later lines focuses on extending disease control while managing resistance and maintaining quality of life. After progression on first- and second-line endocrine therapies—often paired with CDK4/6 inhibitors—clinicians consider targeted agents such as PI3K, mTOR, or AKT inhibitors for patients with appropriate genomic alterations. Select oral SERDs also provide alternatives for tumors with ESR1 mutations. Ongoing research continues to refine optimal order, combinations, and biomarker-driven selection to overcome resistance mechanisms. Ultimately, later-line therapy requires a personalized, evolving strategy that integrates molecular insights, emerging data, and patient-centered goals to maximize therapeutic benefit.