Prospective Evaluation Of High-Dose Systemic Methotrexate In Patients With Breast Cancer And Leptomeningeal Metastasis

Inclusion Criteria

• •Adults (male and female) age \>18
• •Eastern Cooperative Group (ECOG) Performance Scale 0-1 (see Appendix I)
• •Histologically or cytologically confirmed invasive breast cancer of the following subtype:
• •TRIPLE NEGATIVE (ER-negative, PR-negative, and HER2-negative disease). Triple-negative patients will be defined per ASCO-CAP Guidelines.
• •HER2-POSITIVE: HER2-positive patients will be defined per ASCO-CAP Guidelines.
• •HORMONE REFRACTORY: Patients with ER/PR-positive disease according to ASCO-CAP guidelines above may be considered if they have disease progression after two lines of hormonal therapy (administered in the adjuvant or metastatic setting), or are deemed clinically hormone-resistant taking into consideration the rate of progression of disease or a short interval of time on first line hormonal therapy before progression. Clinically hormone-resistant patients MUST also be discussed with the Study Chair, Study co-chair or designee in advance for approval.
• •NOTE: ASCO-CAP guidelines state that ER and PR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. HER2-positive is defined as HER2 IHC 3+, ISH ≥ 2.0, or average HER2 copy number ≥ 6.0 signals.
• •NOTE: A patient who has a change in receptor status (e.g. PR negative to positive) may be stratified as triple negative or hormone positive, contrary to the most recent receptor testing, for the purposes of the study, based upon the clinical course at the discretion of the Study Chair, Study co-chair, or designee in advance for approval.
• •Cytologic or unequivocal radiographic confirmation of leptomeningeal metastasis by dural puncture and/or neuroimaging with or without known brain metastasis
• •Adequate organ function as follows:
• •Estimated creatinine clearance \>70 cc/min (calculated by Cockcroft-Gault formula) White blood cell counts \>3000 cells/mcL Absolute neutrophil count \>1500 cells/mcL Platelet count \>100,000 cells/mcL Hematocrit \>30% Serum bilirubin \<1.5 x the ULN or \<5x the ULN if secondary to liver metastasis Alanine aminotransferase or aspartate aminotransferase \<2.5x the ULN or \<5x the ULN if secondary to liver metastasis Alkaline phosphatase \<2.5x the ULN or \<5x the ULN if secondary to liver metastasis
• •\- Able to provide confirmed consent