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Leptomeningeal metastasis (LM) most often occurs in the setting of a prior diagnosis of adenocarcinoma (1–3). Among this group of diseases, breast cancer is the most frequently associated malignancy (2–6). Central nervous system (CNS) metastasis from breast cancer follows bone, lungs, and liver as the fourth most common site of disseminated disease (7,8). Unlike patients with other solid tumors, approx 50% of patients with metastatic breast cancer are more likely to die from CNS involvement than from the systemic disease, because of the moderate chemosensitivity of breast cancer (15–18). Approximately 2–5% of breast cancer patients will develop leptomeningeal involvement, which is often associated with other sites of metastatic disease (4–7,9–14). The relative responsiveness of systemic metastasis poses a challenge to the treating physician, because patient survival is primarily dependent on the treatment of the CNS disease (14,19,20). The incidence of LM is also expected to increase, because of the broader application of adjuvant therapy for breast cancer, and the relative impermeability of the CNS to systemic treatment because of the blood-brain barrier (2,21). This chapter will present the accepted therapies for LM, with the understanding that further investigation is needed to determine the optimal treatment strategy.

Modern medicine has made great strides in the advancement of treatment strategies for diseases that were once considered incurable. The treatment of the most aggressive forms of breast cancer (BC), inflammatory breast cancer (IBC), has been included in medicine’s quest for cure. Unfortunately, determining the optimal treatment program for IBC is hampered by several characteristics of the disease, e.g., the rareness of the disease, the lack of consistency in diagnostic criteria, and the inclusion of other stages of BC in clinical trials involving IBC.