Treatment strategies for leptomeningeal disease in patients with breast cancer

Leptomeningeal disease (LMD) associated with breast cancer (BC), characterized by the invasion of metastatic BC cells into the leptomeninges and cerebrospinal fluid, poses a significant clinical challenge. Current management strategies are not curative but rather aim to slow the rapid clinical decline associated with LMD, each with its own set of limitations. For instance, systemic chemotherapy faces delivery barriers while intrathecal administration directly targets the site of disease but struggles with uneven drug distribution, toxicity, and limited efficacy. Radiation therapy, including whole brain radiation, stereotactic radiosurgery, and proton craniospinal irradiation, offers palliative relief, though with varying levels of toxicity. The prognosis for patients with BC-associated LMD remains poor under existing treatment paradigms, highlighting an urgent need for innovative therapeutic strategies and delivery systems. Emerging approaches under investigation include advanced radiation techniques, targeted therapies, and novel immunotherapeutic modalities such as oncolytic viruses. Herein, we examine (1) contemporary treatment approaches for LMD in BC and (2) promising novel therapies that may reshape the management of this devastating condition.