here we go again: How inexact ER status testing is!!! - Page 2

Lani · 07-10-2007, 08:28 PM

Tamoxifen may prevent both ER+ and ER- breast cancers and select for ER- carcinogenesis: an alternative hypothesis.
Breast Cancer Res. 2005;7(6):R1153-8. Epub 2005 Nov 21.
PMID: 16457695 [PubMed - indexed for MEDLINE]

Gerri · 07-11-2007, 08:12 AM

Lani,

Thank you once again for posting. I am still in the learning curve of reading abstracts/articles and just want to clarify the statement below taken from the conclusion of the article you posted.

"Tamoxifen is likely to remain an important chemopreventive agent, particularly in the premenopausal setting. Thus, this hypothesis may help us to consider other combinations of agents for prevention, such as combinations of tamoxifen with small molecule inhibitors that target the EGFR family or novel receptor tyrosine kinases. More importantly, it should encourage the design of prevention interventions in a setting where we can follow biomarkers and prospectively test the hypothesis presented in this paper."

To me this is verification that Tamoxifen is still a viable agent for those of us who are premenopausal HER2+ and ER+. Does this apply to those of us already diagnosed with bc or only as a preventative in the high risk population of possibly developing bc?

I am currently on Tamoxifen and was confused about whether it is appropriate for HER2+ bc. I am still premenopausal (age 53) and have been wondering whether I should push for suppresion of my ovaries so I can switch to an AI. My onc doesn't feel there is enough data to support this yet but has left the decision up to me. If my interpretation of the article is incorrect can you guide me to research that supports switching to an AI?

I really appreciate the time you take to help out those of us who are not as skilled in interpreting the results of the research out there. I am very interested in learning how to search for articles and how to to effectively interpret them. Any suggestions of how to hone those skills?

Thanks again,

Lani · 07-11-2007, 11:10 AM

sorry

more soon, I hope!

Hopeful · 07-11-2007, 01:30 PM

Gerri,

Here is a paper that may interest you: Synergistic Interactions between Tamoxifen and Trastuzumab (Herceptin) http://clincancerres.aacrjournals.or...full/10/4/1409

The conclusion reached is, in the lab at least, this is an effective combination.

Hope this helps,

Hopeful

TSund · 07-11-2007, 04:01 PM

I've always heard that AI's were better for HER2 but that might have been before they were treating early bc with Herceptin, and therefore the HER2 was causing Tamoxifen resistance?

I'm confused as to which is going to be better for pre-menopausal (Ruth).

It's possible she'll be thrown into permament menopause by TCH, but possible not also. She has late menopause in her genes. If she goes AI, then we have to go ovary suppression by drugs or ooph. I know that Tamoixfen is much better for the bones (but harder on the heart?)

Comments?

Becky · 07-11-2007, 04:25 PM

http://breast-cancer-research.com/co.../1/R4/abstract

I knew I would eventually find the article on the small study (only 10 women) in which use of Herceptin changed their bc from ER neg to ER pos (therefore, they then benefited from antihormonal therapy).

Lani · 07-11-2007, 04:25 PM

I have sent a lot of articles on to Jean on the relative merits of various antihormonal treatments for Her2+ER+ bc. Perhaps she can forward some on to you. Gotta go!

Becky · 07-11-2007, 04:29 PM

Terri

I believe that while on Herceptin, tamoxifen is fine but it is not fine if it is used as a single treatment (blocking just the estrogen receptor but leaving the Her2 receptor open and exposed).

After Herceptin is concluded, Faslodex or an AI should be used as Tamoxifen resistance (really doesn't mean that it doesn't work but that another pathway is being employed to make the cancer grow. In our case, Her2 or something else) can occur.

Secondly, there is a fine trial that looked at metastatic women that were ER+ and Her2+. None of the women had been treated yet with anything. Half the women received Arimidex and the other half received Arimidex and Herceptin. The half that got Arimidex and Herceptin didn't have progression for 2 years (versus 9 months with Arimidex only). This convinced me to get my ooph AND helped me convince my onc for 5 extra treatments to keep me on the combo for a full year.

Gerri · 07-11-2007, 04:42 PM

My thanks to Hopeful and Becky for your responses (Lani I look forward to hearing back from you when you get a chance). From the link Hopeful provided it looks like the herception/tamoxifen combo is a good choice, but now that I am done with treatment and am only taking tamoxifen I need to make a decision. Becky, from your signature I know that you had an oomph so you could switch to an AI. What research did you base your decision on? I know my onc will go with what I want but I want to be able to support my position.

Thanks again everyone!

Hopeful · 07-11-2007, 06:09 PM

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 · 07-12-2007, 08:33 AM

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 · 07-12-2007, 12:13 PM

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 · 07-12-2007, 03:51 PM

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 · 07-12-2007, 04:01 PM

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 · 07-12-2007, 06:18 PM

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 · 07-14-2007, 07:34 AM

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

Here is a pretty good Tamoxifen resistance paper.

Gerri · 07-14-2007, 04:43 PM

Thanks Becky for posting that link. I will pass it on to my onc and discuss with her my options.

Lani · 07-21-2007, 09:19 AM

We expect that the cost effective, extremely sensitive, high though-put molecular assay which requires only a few cancer cells could be an assay of choice to replace IHC in clinical labs for determining ER? status in breast cancer tissues once established in a multi-centered prospective clinical study.

Let's hope it happens soon.

Bronny · 08-06-2007, 01:57 AM

After surgery, 18 months ago I was told I was hormone negative, HER2 + so my treatment included AC/taxol Dose dense for 4 months, 33 rads and herceptin for 1 year (due to finish in 2 months).

On my first visit with the surgeon since that time, just recently, he told me that the core needle biopsy said i was 99% hormone positive, yet the surgery tissue results came back strongly 'hormone negative'. Based on this result, he has represented my case in a meeting with other health professionals. A re-testing was also done on both the core and after surgery tissue which produced the same results. Due to this, the oncologist and surgeon want to change my treatment to reflect the core hormone positive results as they think ths biopsy is the most accurate test of the two.

This new treatment will involve tamoxifen and either removing my ovaries (to decrease ER production) or monthly Zolodex injection to stimulate temporary hormone suppression. This is because I have gone back to being pre-menopausal, 6 months after the chemo.

I am in a real quandry as to what to do here and would love a second opinion and/or to see if anyone else has had a similar experience.

Bronny · 08-06-2007, 02:06 AM

After surgery, 18 months ago I was told I was hormone negative, HER2 + so my treatment included AC/taxol Dose dense for 4 months, 33 rads and herceptin for 1 year (due to finish in 2 months).

On my first visit with the surgeon since that time, just recently, he told me that the core needle biopsy said i was 99% hormone positive, yet the surgery tissue results came back strongly 'hormone negative'. Based on this result, he has represented my case in a meeting with other health professionals. A re-testing was also done on both the core and after surgery tissue which produced the same results. Due to this, the oncologist and surgeon want to change my treatment to reflect the core hormone positive results as they think ths biopsy is the most accurate test of the two.

This new treatment will involve tamoxifen and either removing my ovaries (to decrease ER production) or monthly Zolodex injection to stimulate temporary hormone suppression. This is because I have gone back to being pre-menopausal, 6 months after the chemo.

I am in a real quandry as to what to do here and would love a second opinion and/or to see if anyone else has had a similar experience.