her2+ breast cancer not as good as disrupting Blood-Brain Barrier as triple negative,

Lani · 01-22-2010, 09:59 PM

basal type

ABSTRACT: Disruption of the blood brain barrier by brain metastases of triple-negative and basal-type breast cancer but not HER2/neu-positive breast cancer
[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.

bejuce · 01-23-2010, 01:03 AM

So if HER-2+ brain metastasis preserve the BBB, that's definitely a good thing, right? Not sure if I am interpreting this correctly.

Ellie F · 01-23-2010, 04:49 AM

Thats how i interpreted it as well!
Am i just wishful thinking??

Ellie

Becky · 01-23-2010, 07:39 AM

I think its not as good a thing in that if it were disrupted, Herceptin could pass the blood brain barrier as well as other chemos that are too large to pass.

Barbara2 · 01-23-2010, 09:40 PM

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.

Or, does "disrupt the BBB" mean metastasis, and that her2+ breast cancer is less apt to enter the brain?

Laurel · 01-24-2010, 11:37 AM

Quick and dirty here, I think this is reflecting metastatic BC to the brain in all cases. However, triple neg & basal type mets to the brain interrupt, weaken if you will, the BBB perhaps allowing chemo and other anti-neoplastic agents to cross over the barrier to reach cancerous cells within the brain. From this research it seems Her2 is kind enough to not disturb the effectiveness of our BBB and therefore it remains intact and completely able to exercise its intended function of keeping substances from passing through to the brain. Which in short makes it difficult to kill the wretched stuff off via chemo and large molecule agents.

Have I mentioned just how much I hate HER-2 NEU??????????

Lani · 01-24-2010, 12:54 PM

sorry I was travelling and so unable to access the web and answer your questions promptly. Luckily Becky and especially Laurel stepped in and interpreted the article(and even explained in more detail why, in the case of Laurel)correctly.

Nevertheless, it does seem that those with her2+ brain mets DO BENEFIT BY having/continuing herceptin as part of their regimes. I have posted many papers supporting the continuation in the face of brain mets. Whether the suppression of mets outside the CNS prevents them from sending some kind of signal that encourages the growth of the brain mets or for some other reason herceptin remains helpful in the face of brain mets. This paper seems to show it is NOT because herceptin eventually gets throught the blood-brain barrier as the brain mets somehow make it less effective, but this IS AS AN AGGREGATE.

It may be that some her2+bc but not others DO make the BBB more permeable(able to be passed through) but that this % of her2+ bc is not enough of the whole of her2+ bc to make the average her2+ bc brain met
cause BBB disruption as often as triple negative or basal bc brain mets do.

Thanks, Becky and Laurel!!