here we go again: How inexact ER status testing is!!!

[Hopeful]

I have been looking for the paper I read that talked about one of the mechanisms for Tamoxifen resistance in Her2+ bc patients to give the citation. Apparently, in the lab (could have been in mice, not sure) they found that the ER receptor, normally located in the cell nucleus, was displaced to the outer surface of the cell by Her2 signaling. Apparently, the ER receptor has to be in the cell nucleus for Tamoxifen to work. Blocking the Her2 receptor with Herceptin caused the ER receptor to move back to the nucleus, where it belongs, and allowed the Tamoxifen to work. When I find this paper (as I am looking for another one, that's how it always happens) I will post the link.

Hopeful

[TSund]

Here's maybe a dumb question; does Tamoxifen work differently for POST-menopausal women?

Also, I've been pondering why hormonal positive tumors are MORE common in post-menopausal women. Has there been any determination on why that would be?

Is there any statistical trends different for er+ in menopausal women than post?

[Hopeful]

Terri,

The mechanism of action of Tamoxifen is the same in both pre- and post-menopausal women: it is a weaker form of estrogen than the body's own that competes for the estrogen receptor on the cell. One reason that pre-menopausal ER+ women are rx chemotherapy is to shut down the ovaries. This can be achieved hormonally or via their removal, however. When a woman's ovaries no longer produce estrogen, the body still requires it and a single enzyme converts aromatase into estrogen. Aromatase inhibitors prevent this action, and work via strictly estrogen deprivation - there is no circulating estrogen to attach to the receptor. AI's are thought to be more effective in treating Her2+ bc.

I don't know why ER+ tumors are more common in postmenopausal women, not do I recall reading a paper that addresses this. It seems counterintuitive, but there it is. I think if science could find an answer, we would be further along the road to prevention.

Here is a link to a terrific site with excellent information on all aspects of bc: http://home.earthlink.net/~ckane/brca.htm. There are lots of articles on hormonal therapy cited, one of them may even have those stats you are seeking.

Best of luck to your wife (and you!) with her treatment plan,

Hopeful

[TSund]

Hopeful,

You have great information. Thank-you! Shows hard work on your part.

I cannot remember if you were ER+PR+, but I am wondering what you know about the progesterone end of things. The fact that ER+/PR+ does better than ER+/PR- is another counter-intuitive for me. (if indeed progesterone is BAD for this type of bc) I read very little about the PR+ element, in fact many sources ONLY refer to ER+ without distinguishing between ER+/PR- and ER+/PR+

Are you familiar with Dr. Lee's books on natural progesterone? Much of what he says makes sense, (but rather rattling). If progesterone does work to eliminate estrogen dominance, than it seems to counter the advice on estrogen. Or just the lack-there of re: progesterone (NATURAL)

His bc book, however, says nothing on PR+ tumors one way or the other, at least that I can find.



TRS

[TSund]

Wow, if this is the way that Tamoxifen works, then it seems to fly in the face of advice about phytoestrogens; which are exactly that: very mild forms of estrogen. ...which I believe is why the belief they have protective elements re: breast cancer.

?????

[Hopeful]

Terri,

Most of the time, I am just fairly good at remembering where I read something.

Just to throw a wrinkle into things, there is some evidence that, for at least some Her2+ ER+ patients, Tamoxifen acts as an agonist, rather than an antagonist. My personal belief is that this is one of the reasons virtually all Her2+ patients score highly on the Oncotype Dx test, which was validated (retrospectively) in a set of patients ER+ node negative treated only with Tamoxifen. (I want to stress that this is my personal opinion only; I haven't seen anything written on it).

As to the PR- phenotype, there are a lot of articles written about it; it tends to be Tamoxifen resistant; if you google "Tamoxifen resistance" you will get a lot of hits on articles that discuss it.

I am providing links to some older threads where a lot of these issues have been discussed:

http://her2support.org/vbulletin/sho...&highlight=PR-

http://her2support.org/vbulletin/sho...&highlight=PR-

http://her2support.org/vbulletin/sho...&highlight=PR-

http://her2support.org/vbulletin/sho...&highlight=PR-

The last link above contains some research I did some months back concerning the prognostic significance of PR+ vs. PR-, ER+ bc. I am ER+ (80%) and PR+ (50%). I am not familiar with Dr. Lee's books.

Hopeful

[Becky]

http://erc.endocrinology-journals.or.../full/11/4/643

Here is a pretty good Tamoxifen resistance paper.