The uncertainty of HER2+, AIB1, and tamoxifen

I read the posts about this question (which are pretty much on the next page now). I know Iressa is in clinical trial to see if it can be used to restore tamoxifen's efficacy. I chose to quit tamoxifen and am considering the alternatives.

What I don't understand is at what point does the manufacturer have to start putting a warning about this question on their package insert?

None of my doctors mentioned the question to me. I had to take the information to my internist, and he talked with my oncologist about it. So far the only feedback I have received is that "Well, women are now generally being taken off tamoxifen after 2 years and put on an aromatase inhibitor, and you are almost at 2 years, so if you want to switch, it is okay."

Uhhhh.... if they think the combination of HER2+ and AIB1 is more likely than not to be dangerous in combination with tamoxifen, shouldn't they be testing women to see which ones are HER2+ and have AIB1?

Am I being dense?? Somebody help me out? Why does a HER2+ bc patient have to be the one to figure out that this question is out there? (I may be naive but I thought the whole idea of doing research was to help US out....)????

I am ER & PR negative, so I have only scattered understnading of this question.
Does Raloxifene have the same problem as Tamoxifen for those with AIB1?
Maybe I am just adding another question to the mix, but i thought this was supposed to be a better drug.
Maybe one of the 'research types' here will find any current published info?

You mention Ralefoxin (sp?) but that is the brand name for Evista. It is in a different class of drugs than both Tamoxifen and Femara. My mother who does not have bc is on Evista to help prevent bc and promote bone growth. There is also the STAR study for woman at risk on either Evista or Tamoxifen.

The research did not raise any question about any other drug than tamoxifen, but your question is reasonable since both tamoxifen and raloxifene are both SERMs.

Also, my understanding is that the question involved only those who had high levels of HER2 as well as high levels of AIB1.

Because only about 30% of bc are HER2+ and an even smaller group of those who are HER2+ have high levels (HER2+++), then the question is how many of the group thath are HER2+++ happen to also have a high AIB1 level?

The focus of this board is HER2 and any questions or concerns regarding HER2, and I believe this certainly is (or should be) one of them.

Hey Alaska Angel,

I'm not sure I have much to add to this thread other than that I'm completely sympathetic. I don't want to bash oncologists here--there are many good ones, I'm sure!--but there are also loads of them who should really be called, as Neil Ruzic does in his book Racing to the Cure, "chemotherapists." They admninister the same treatment to people who appear ot have the same disease, without asking many questions. I'm sure this is largely due to the pressures of seeing too many patients.

In my partner Rachel's case she had an oncologist originally who wouldn't give her herceptin off-protocol but WOULD give her the name of another oncologist who would. She made it clear that her own reasons for not giving it had a lot more to do with professional issues and community standards rather than what might be best for Rachel.

As for her2 and hormonal treatment, it's been clear for awhile, I think, that women with her2 positive breast cancer were at best getting not much benefit from tamoxifen, at worst, possibly, being harmed by it. But that is mostly based on in vitro evidence and oncologists (and drug companies) won't do a thing until they have lots of data from a million different Phase III clinical trials. And there will never be enough women who are her2+ and er/pr+ to launch those kinds of trials.

Aargh.

Jeff

I did a Google search and came up with this:
Conclusion: High AIB1 levels in breast tumors, especially those with low Her2, predict a more indolent course in breast cancer patients not receiving adjuvant therapy. But in patients receiving TAM, high AIB1, especially those with high Her2 have strikingly worse DFS, perhaps due to increasing agonist effects of the drug. If validated, these markers together might identify patients for alternative treatments.

I think it means that Tamoxifen can act like an estrogen, in stead of an estrogen antagonist in some situations. Maybe that's why my oncologist wants to start me on Aromatase Inhibitors. They seem to work better in Her2 pos patients.

And I found another site that gives some info in understandable English. http://www.usnews.com/usnews/health/briefs...r/hb040917b.htm

Thanks for helping me figure this one out, Jeff.

But...

If there isn't enough clout or enough reason to be terribly concerned about ER+ and HER2+, how was there enough influence to get the clinical trial going to find out if gefitinib works to reverse the process and restore tamoxifen's effects?

A.A.

Hey A.A.

I think, from my quick searches, that there is a decent amount of interest in er+/her2+ not because it is such a rare combination, but because it is so (relatively) target-able. There are a bunch of folks trying to figure out the best combination of therapies for the targets.

That said, I also think that there is some theoretical work being done that suggests that things out there like gefinitib (and maybe herceptin) might ultimately be used in er-/pr- women to somehow create receptor positivity and then give the person hormonal options...

Best,
Jeff