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.