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

Abstract

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 carcinomatosis, the median serum level of trastuzumab after WBRT was 17,431 ng/ml and 356 ng/ml in CSF (ratio 49:1). Conclusion: These data indicate that the BBB prevent trastuzumab to reach adequate concentrations in CSF. These levels are increased under conditions of an impaired BBB, as is known for meningeal carcinomatosis and for patients receiving WBRT. The new test system in this pilot study provides the basis for the evaluation of radiotherapeutic strategies which allow most favorable penetration of trastuzumab into the CNS in patients receiving concomitant trastuzumab for HER2-overexpressing metastatic breast cancer. [Table: see text]