 Currently, HD-MTX is included in the NCCN Guidelines for LMD and is used intermittently at Johns Hopkins and cancer centers across the nation for LMD in breast cancer. These recommendations, however, are more representative of the lack of available therapies for LMD as opposed to strong evidence-based data. Only two retrospective studies have suggested that HD-MTX may be an effective option for treating central nervous system CNS metastasis, both with substantial methodological limitations. 