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The treatment of brain metastasis from breast cancer: role of blood brain barrier disruption and early experience with trastuzumab

Rose Marie Tyson, Dale F Kraemer, Matthew A Hunt, Leslie L Muldoon, Peter Orbay, Leeza Maron, Kristoph Jahnke and Edward A Neuwelt

Background: Therapeutic approaches in the treatment of metastatic systemic brain tumors from breast cancer have improved. As patients live longer, the potential for CNS sanctuary disease increases. Metastases to the brain are diagnosed in breast cancer patients at a rate of 10 to 20%. Median survival is only 3 to 12 months with current standard therapies of whole-brain radiotherapy, surgery and stereotactic radiosurgery, and can vary with the type of treatment given. Chemotherapy and immunotherapy using trastuzumab may be more effective against brain metastases if delivery to the tumor can be improved. Results: The treatment was well tolerated with acceptable bone marrow toxicity. Median overall survival was 45.4 weeks and the majority of patients achieved symptomatic relief with reduction of steroids. Methods & objectives: We evaluated the use of osmotic blood–brain barrier disruption chemotherapy, with or without monoclonal antibody, for the treatment of brain metastases from breast cancer. We are interested in the prospective evaluation of the combination of a monoclonal antibody, trastuzumab, with enhanced delivery of carboplatin and methotrexate chemotherapy. Discussion: The use of carboplatin and methotrexate with blood–brain barrier disruption showed efficacy in the treatment of metastatic breast cancer to the CNS. This is comparable to other modalities, and without cognitive loss. Quality of life is improved with the withdrawal of steroids. Conclusion: The long-term goal is to use combined chemotherapy and immunotherapy with radiosurgery to increase survival and avoid complications from other treatments.