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Clinically apparent brain metastases occur in as many as 16% of patients with metastatic breast cancer. Therapies for these patients include lesion excision, whole-brain radiation, and stereotactic radiosurgery. To date, chemotherapy and endocrine therapy have provided limited or no benefit, presumably because the blood-brain barrier (BBB) allows tumor cells to enter through the vasculature but excludes most systemic agents with high molecular weights. The emergence of anti-HER2 therapies, particularly trastuzumab (Herceptin), has lengthened survival among patients with HER2-positive breast cancer; however, as many as one third of patients who receive trastuzumab develop brain metastases. This high incidence could be explained by the longer…