10747 Background: trastuzumab (Tz), a humanized anti-HER-2/neu antibody, has been shown to improve survival in patients with HER2-positive breast cancer. A high incidence of brain metastases (BM) has been noted in patients receiving trastuzumab. Here we report 4 cases of HER-2 positive advanced breast cancer patients who developed BM while on TZ therapy. CASES all 4 patients were treated initially with a combination of taxane-trastuzumab followed by maintenance trastuzumab. Tumors were classified as HER-2 over expressing if they were scored 3+ by immunohistochemistry or showed amplification by fluorescence in situ hybridization. Mean age at diagnosis was 48. Mean duration of trastuzumab therapy prior to BM was 20 months. All patients had achieved a complete remission of extracranial disease at the time of BM diagnosis. Mean number of intracranial lesions as determined by magnetic resonance imaging was 4. Treatment included radiosurgery, surgical resection, whole brain radiation, temozolomide, high dose methotrexate, thalidomide and in one patient, intra-arterial chemotherapy. All 4 patients are alive at the date of last follow-up (median =3 years) after BM diagnosis. CONCLUSIONS this report suggests that patients who develop BM after trastuzumab can have a relatively long survival rate. The importance of a multidisciplinary approach to these patients cannot be overemphasized. Development of BM on TZ therapy does not represent resistance to TZ, but instead likely reflects the inability of TZ to cross the brain-blood barrier. Further research in this area is needed to optimize management while minimizing late effects. In this regard, alternatives to whole brain radiation should continue to be studied. In addition, the role of prophylactic cranial irradiation and the search for drugs that target HER-2 and cross the blood-brain barrier should be investigated. No significant financial relationships to disclose.