Disruption of the blood brain barrier by brain metastases of triple-negative and basal-type breast cancer but not HER2/neu-positive breast cancer.
BACKGROUND
Generally, the blood-brain barrier (BBB) of brain metastasis was thought to be disrupted.


METHODS
We retrospectively performed immunohistochemical staining for glucose transporter 1 (GLUT1) and breast cancer resistance protein (BCRP) to evaluate the status of the BBB in resected brain metastases. Associations between expression of GLUT1 and/or BCRP and the immunohistochemical profiles of breast cancers, such as the statuses of hormone receptors, human epidermal growth factor receptor 2 (HER2/neu), and a basal-type marker (cytokeratin 5/6, HER1), were also analyzed.


RESULTS
The study included 29 breast cancer patients with brain metastasis who had undergone brain tumor resections. Among the 29 patients, there was no expression of GLUT1 and BCRP in the intratumor microvessels of 9 (32%) and 11 (38%) patients, respectively. There was no expression of both GLUT1 and BCRP in 8 patients (28%). The expression of GLUT1 was significantly associated with that of BCRP (P < .001). A positive correlation was observed between the expression of GLUT1 and/or BCRP and brain metastases of HER2/neu-positive breast cancer (P = .012), while a negative correlation was observed between the expression of GLUT1 and/or BCRP and brain metastases of triple negative or basal-type breast cancer (P = .014 and P = .003 for triple negative and basal-type, respectively).


CONCLUSIONS
Brain metastases of triple negative or basal-type breast cancers may often disrupt the BBB, whereas brain metastases of HER2/neu-positive breast cancer tend to preserve the BBB.
Yonemori
Kan
K
Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
Tsuta
Koji
K
Ono
Makiko
M
Shimizu
Chikako
C
Hirakawa
Akihiro
A
Hasegawa
Tadashi
T
Hatanaka
Yutaka
Y
Narita
Yoshitaka
Y
Shibui
Soichiro
S
Fujiwara
Yasuhiro
Y
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000328:Adult; D000368:Aged; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001932:Brain Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D051272:Glucose Transporter Type 1; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C116614:ABCG2 protein, human; C495677:SLC2A1 protein, human; C508053:ERBB2 protein, human