Central Nervous System Metastases in Breast Cancer

Breast cancer metastasizing to the central nervous system (CNS) encompasses two distinct entities: brain metastases involving the cerebral parenchyma and infiltration of the leptomeningeal space, i.e., leptomeningeal disease. CNS metastases affect 10–15% of patients with hormone receptor-positive-status and nearly one-half of those with HER2-positive and triple-negative breast cancer with distant metastatic disease. Significant clinical morbidity and heterogeneous penetration of the blood–brain barrier by systemic therapies contribute to the poor prognosis associated with brain metastases. Recent advances in radiotherapy, including stereotactic approaches and morbidity-reducing strategies such as the use of memantine and hippocampal avoidance in whole brain radiation, coupled with the development of more effective CNS-penetrant systemic therapies, including small molecules and antibody–drug conjugates, have significantly improved patient outcomes. Consequently, patients with breast cancer CNS metastases have improved survival compared to prior decades, and longitudinal care has become increasingly complex, necessitating a multidisciplinary approach to achieve optimal outcomes for patients.