Brain metastases in HER2-overexpressing metastatic breast cancer: Comparative analysis of trastuzumab levels in serum and cerebrospinal fluid

1525 Purpose: Patients receiving trastuzumab for HER2-overexpressing MBC suffer from an increased risk to develop BM despite responsive visceral disease. The present pilot study was conducted to explore trastuzumab levels in S and CSF of MBC patients afflicted with BM, and to evaluate whether radiotherapy will lead to impairment the blood-brain barrier (BBB) to allow penetration of trastuzumab into CSF. Methods: Patients with BM from HER2-overexpressing MBC (IHC; DAKO Hercep Test) were included. Trastuzumab levels in S and CSF were determined at different time points by a newly developed immunoenzymatic test for functional, reactive trastuzumab. Results: Six out of 8 eligible patients were evaluable. Prior to whole-brain radiotherapy (WBRT), the median trastuzumab serum level was 52,054 ng/ml compared to a median CSF level of 124 ng/ml (ratio 420:1). After completion of WBRT, the median level of trastuzumab was 20,185 ng/ml in serum and 226 ng/ml in CSF (ratio 76:1). In two cases of concomitant meningeal ...