Existence of blood brain barrier in brain metastases with breast cancer

Abstract

13513 Background: Increasing of the incidence of brain metastases in breast cancer patients is an important clinical problem. Brain metastases are refractory to chemotherapy due to existence of blood brain barrier (BBB). However, the structure and mechanism of BBB is not fully understood. We examine expression and localization of BBB with representative immunohistochemical markers of glucose transporter 1 (Glut-1) and breast cancer resistance protein (BCRP) in brain metastases with breast cancer patients. Methods: Between 1999 and 2006 at National Cancer Center Hospital in Japan, 29 patients who had metastatic breast cancer underwent metastatic brain tumor excision. Glut-1 and BCRP expression of brain metastases in 29 patients were examined by immunohistochemistry. We also performed the immunohistochemical analyses for estrogen receptor (ER), progesterone receptor (PgR), HER2 and phosphohistone-H3 (PHH3). If intratumoral microvessels in brain metastases were negative for both Glut-1 and BCRP, we regarded as absence of BBB. Results: Nine (31%) and eleven (38%) out of total 29 in tumor microvessels were negative for Glut-1 and BCRP, respectively. Eight (28%) were negative for both Glut-1 and BCRP. There was significant association between Glut-1 and BCRP (p=0.0001). Glut-1 was significantly associated with HER2 (p=0.004). BBB had no correlation with ER and PgR. PHH3 was not associated with BBB. Conclusions: BBB was absent in 8 (28%) out of total 29 in brain metastases with breast cancer. Although further studies are warranted, drug bioavailability to tumors may be also different in brain metastases of breast cancer. No significant financial relationships to disclose.