of that subpopulation of her2+ bc patients who have brain mets

[Lani]

those who are ER+ live much longer , both from time of diagnosis and from time of developing brain mets, than those who are ER- according to this study

I posted an article about it earlier that was confusing and didn't match what the poster presenter had told me in person

This article seems much more straight- forward

http://www.breastcancersource.com/breastcancersourcehcp/6096_31638_0_0_0.aspx?

[MJo]

I know herceptin doesn't cross the blood-brain barrier, but I wonder if taking Arimidex will "starve" any cancer cell that might have found its way to my brain (Not!). Does Arimidex shut off estrogen in the brain? I am glad to be ER/PR+, but I believe that science will find better treatment for the negs. soon, just as they created Herceptin and Tykerb for us Her2 positives.

[Mary Anne in TX]

Thanks Lani! This was crystal clear! Protect the ol' brain every way we can!

[StephN]

Being ER/PR - I was off those figures by a mile. Except time to initial progression. After that it was nearly 3 years for brain mets to be detected. And I have not died 3 years after that time. Even though I am just one person who is beating the stats above quoted, I post so people can have hope.

83 women is a small study to my way of thinking. And it does NOT say how those mets were treated, how many they had and a lot of other info is missing. But that is a synopsis and not the actual poster.

[Lani]

the answer is it is unknown

there are several possibilities (and more I haven't thought or read about):
1)the arimidex is small enough to get past the blood brain barrier but the herceptin isn't and if there are bc cells in the brain which are not dormant
their ER pathway is "downregulated" by estrogen deprivation, but since their her2 pathway may not be blocked (Herceptin not crossing the blood-brain barrier) while ER is relatively blocked the cancer may increase the her2 pathway activity via crosstalk

2) the arimidex gets in but the crosstalk story is too simplfied and her2 does not get increased ( but IGFR, AKT, and other downstream pathways could still provide a "backdoor for the puppy wanting to get out" if the cells awake from dormancy and divide) This also may not happen--all those pathways and their positive and negative feedback loops haven't been figured out yet

3) Arimidex, its metabolites, or other entities it might complex with may not get through the blood-brain barrier. I have not looked up how many Daltons it is (measurement of size --molecules over a certain number of Daltons don't cross the blood-brain barrier) The fact that brain mets of ER+ her2+ tumors are not as agressive may relate to the antiestrogen treatment patients are receiving. It would be interesting to see if any of the patients did not receive antiestrogens (doubt), which took tamoxifen (felt to be less effective in those on her2 WHEN NOT on herceptin) vs AIs vs Faslodex

4) I have asked oncologists and drug company reps at SABCS last year whether faslodex crosses the blood brain barrier and they did not know.

It makes estrogen receptors fall off every cell in the body irreversibly--OK for nonbrain cells as they are constantly replaced throughout life and will come back on cells when treatment ends. Brain cells rarely get replaced so IF faslodex crosses the bloodbrain barrier, those brain cells will be deprived of what makes women smarter than men (sorry for the infusion of humor, but I couldn't control myself). Seriously, estrogen has an important role in the central nervous system.

Perhaps I am too cautious/pessimistic in painting my scenarios and armidex keeps the micrometastases in the brain at bay or creates an inhospitable environment for them, but the speed with which brain mets occurs in her2+ER+ patients (less than the 66 months or so before antihormonals might first be stopped)
makes me think they do not provide 100% protection--but then, perhaps those people are innately antihormonal resistant or it took just that long for acquired resistance to occur, or perhaps the time to recurrence was determined by the "angiogenic switch" and only then did the dormant cells start to multiply and before that presence/absence of estrogen wou;dn't have made a difference.

The experiments to tell which of these scenarios (or some other) applies are ongoing. We must do what we can to support that research!



4)

[Believe51]

Thanks Love for keeping my perspective, it is too vague a study for me to hold any stock in also. We must remember when reading studies and statics that they are just that. I think it is important to ask ourselves those simple vital questions, personally I have a hard time listening to most (not denial)! No one will give us a death sentence of time. Besides, Mighty Oak will prove some of the past studies wrong!! If I listened to stats and what-not he would not even be here right now to read this!! Let us all prove 'em wrong.>>Believe51

[Lani]

because I knew I would be asked about it

Her poster left off how long survival was from time of first mets (if not brain)

I told her how important it was to put that in, as beancounters and people who write up NCCN guidelines and government healthcare services utilize this information to make decisions regarding who does and doesn't get to have prophylactic brain MRIs to detect tumors early when they are small and not so numerous and hopefully amenable to Cyber/gamma knife.

She understood my point immediately and promised to go back and review all the Mayo sites figures again and be sure that information would be included when the information was published.

[StephN]

Thanks for being "proactive" on that study.

We know you are one sharp cookie, and very little gets by you.

My brains mets were not small especially the 3cm one, which grew quite quickly. But it was still in the size range to be treated by Gamma Knife. Just caught because of yearly brain screening and I had no complaints of symptoms.

Being a bunch of survivors here, we are quick to point out flaws or holes in studies. More of a common sense thing, than real knowledge of the intricacies of collecting statistics.