High-dose intravenous methotrexate in the management of breast cancer with leptomeningeal disease: Case series and review of the literature

Leptomeningeal metastasis (LM) in breast cancer is associated with significant morbidity and mortality. While there is currently no standard therapy, treatment options include craniospinal radiotherapy, intrathecal chemotherapy and systemic chemotherapy. Craniospinal radiotherapy has not demonstrated improved survival and intrathecal chemotherapy is often poorly tolerated due to associated neurotoxicity. The use of systemic chemotherapy can be limited by inadequate central nervous system penetration. High-dose systemic methotrexate administered intravenously (HD-MTX), has been reported to improve quality of life and provide durable remissions for LM in breast cancer. We present three cases of metastatic breast cancer and LM with prolonged survival after administration of HD-MTX. Based on our observations and review of the literature, HD-MTX seems to be a viable treatment option for patients with LM in breast cancer, and in select cases, the use of HD-MTX, as part of a multimodality treatment plan, may be associated with prolonged survival.