HER2+, ER+, PR+ and are taking Tamoxifen.

[astrid]

Was wondering how many pre menopausal women are HER2+, ER+, PR+ and are taking Tamoxifen?

[Sammy]

I am her2+,PR+,ER+ and pre menopausal . Not taking tamoxifen though.

[karenann]

I am triple + and I was pre menopasal before chemo and now it seems I am in menopause. I am not taking Tamoxifen; I am on Aromasin.

Karen

[Susan2]

I was triple positive and took Tamoxifen. However, I'm finished with my 5 years now.

[dberg]

I am triple positive, 47, premeno before chemo, but haven't had a period since Sept 2004. I'm going to have a discussion with my onc AGAIN, about switching, especially in light of the articles I was referred to by Astrid and Al.

[snoopy]

Triple positive. Premenopausal before chemo. Took Tamoxifen whilst I was on Herceptin. Before years herceptin finished I had an oophorectomy so I could have Arimidex

[Bev]

Triple pos, 47, chemopause. Have been on tamox 2 mos. I'll be switching to an AI less than 3 mos, 1 year anniversary of chemopause, if estradiol levels check out. BB

[astrid]

I went to a lecture last night from a local oncologist who was asked to speak at our breast cancer support group on anti-estrogen therapy for Breast cancer. He asked if there were any questions, so of course I said “Yes, I am triple positive and have recently read that the combination of ER+ and HER2+ is creating Tamoxifen resistance in those patients. I have also heard that sometimes Tamoxifen actually acts like an activator instead of an antagonist. My ONC assures me these are only animal/lab studies and not done on humans. Is this correct?”

His lecture was fascinating. He covered everyone’s questions in his explanation on Tamoxifen and the newer Aromatase Inhibitors (AI). He compared the two and explained why AIs are not effective for pre menopausal women. As, I am pre menopausal there is no standard treatment other than Tamoxifen. The reason AIs will not work for pre menopausal women is that the ovaries and the pituitary gland have feed back to each other so when an AI tries to shut the estrogen down the pituitary gland says “Hey, I need more estrogen and the ovaries respond and create more. This does not happen when the ovaries are shut down either chemically or by menopause because there is no one home to answer the pituitary gland when it demands more so it basically shuts up” AIs are not strong enough to shut down all the estrogen that the ovaries produce. They work on the other systems that create estrogen such as your skin and adrenalglands.

He then went into what is becoming a newly discovered problem and that is the cross talk between the estrogen receptor and the HER2 receptor. He confirmed that these are only animal/lab studies and not done on humans; however what they have found is that when you add the biologic therapy of Herceptin that the Herceptin blocks the cross talk because it binds to the HER2 protein and blocks it from dividing and therefore makes the Tamoxifen effective again. So while on Herceptin, I will not have to worry about Tamoxifen activating residual cancer cells. He also said that the more ER+ you are the more effective Tamoxifen is. I am 16% ER+, so my chances of reoccurrence and DFS (Disease Free Survival) are improved by approximately 16%.

I start Tamoxifen today, and today I feel good about the drug.

[AlaskaAngel]

The lecture sounds very interesting. Thanks for sharing it and explaining it so well.

I still have a few questions about it. Maybe someone who understands cross-talk better than I do could comment on them.

1. Herceptin doesn't work on some varieties of HER positivity other than HER2. So would there still be a problem in terms of cross-talk and tamoxifen, as long as HER2 was blocked by Herceptin?

2. Apparently Herceptin does not work for a significant number of those who are HER2 positive, or who become resistant to Herceptin. Would there still be a problem in terms of cross-talk and use of tamoxifen for them?

A.A.

[dberg]

Astrid, thank you for sharing the lecture information. I recently finished my year of herceptin and am taking just tamoxifen now. I have read good reports about coming the two, but what happens when you quit the herceptin?

[astrid]

dBerg, I do not know what happens when you quit Herceptin. The bad thing is I am not sure that the ONCs know what to do either. This cross talk issue is very new. I have several published papers about this and most of the research is done for post menopausal women in labs and there are no real answers yet. If you are post menopausal, discuss with your ONC switching to an AI and Calcium supplement. If you are Pre menopausal discuss with your ONC Lupron injections to shut down your ovaries and then switch to an AI. I am by no means an expert. Please discuss this with your ONC. As Alaska Angel points out, There are different forms of HER +.

[Becky]

you are right that if you might also be Her1+ or Her3+ there would be cross talk between the estrogen receptor and a Her1 or3 receptor and that could render tamoxifen resistance even though the Her2 receptor is blocked by Herceptin. However, EVERYTHING loves the Her2 receptor (to cross talk with - what an attractive fellow Her2 is). So, if you have blocked Her2 with Herceptin and then blocked ER with tamoxifen, there is alot of interference on the surface of the cell to deal with - alot of molecules getting in the way for Her1 to have to cross talk to itself (and from what I have read, Her1 likes to cross talk with others and not itself). Also, I went to a presentation at ASCO on ER+ but PR negative. I went because that is what I am and it is pretty unique. If you are PR+ it is better yet since if you are PR- you also tend to be Her2+ (like me) but if you are also Her2 negative, you are probably Her1+ (because only Her2 likes to also cross talk with itself but everything else likes to cross talk with something different) so if ER+ but PR neg - something else is there and if it isn't Her2 then it is Her1 (but some Her2+ are also Her1+ but if they are ER+ as well, they probably are not Her1+ (or only mildly so)). So, this paper said if you are only ER+, tamoxifen does not seem to work (had lots of results) and this is because these women's tumor blocks tested positive for Her2 and/or Her1. These women tended to be younger or African American.

Lastly, some women do not respond to Herceptin because of several factors:

1. they are actually also Her 1 or Her 3 as well so that continues to drive the cancer

2. if they were hormone negative, they may have changed to positive

3. they may have the truncated version of Her2 (no receptor on the outside for Herceptin to bind so the receptor is always on the "on" position - Tykerb could work here as it works inside the cell and not outside the cell).

Becky

[AlaskaAngel]

One reason I did the poll was to get more of an grasp on just what percentage of HER2's would tend to be premenopausal at diagnosis.

The poll would indicate that there are likely to be a much higher percentage of patients who are HER2 positive and who are going to end up on tamoxifen at least initially, than would be true for the larger group of all bc. At least some patients may be helped into menopause by ovarian ablation (surgical or chemical). Very, very tough choices for those in the 20-30 and 30-40 age range to make.

There seems to be little if any effort made to allow each woman to consider this particular issue when making the choice of treatment. But I have to say that this appears to me to be a very important issue for HER2 positives to consider -- whether or not most medical providers are actively talking about it with patients.

The other point that is important for HER2's to consider is the effectiveness of tamoxifen. My understanding is that in the entire range of bc (i.e., not just HER2's), tamoxifen works less than 50% of the time.

I wonder what percentage of the group of all bc patients for whom tamoxifen does not work "happen" to be HER2-positive, even HER2++. It is interesting that this does not appear to be the case if one is also ER+ and PR+.

My feeling is that this is important enough that there should at least be some effort made to provide some information about this that is specific to HER2 positives in the package insert for tamoxifen.

AlaskaAngel

[sabpri]

with my weird pathology, as I had 2 Tumors, one that was ER/PR+ and weak Her2 and not amplified (I think that means it was negative!). The other Tumor was Triple Negative with an ***. The * stated that while the Her2 score = 0, a small subset, like 10%, tested Her2+++ and was amplified. No one has really been able to decode this for me, but I think it means the stinker was starting to change from triple negative to Her2+ when we caught it. So basically I am hormone and Her2 positive.

I was 36 at the time and even though I had kids, I went through a lot of infertility to have them and the thought of being denied the ability to have children again by removing my ovaries was devastating. Knowing that I am a major worry wart and that I need to be around for my 2 year old twins and 4 year old daugther, I went ahead and had my ovaries removed so I could take the AI (Arimidex). Everything I read seemed to point to that option being better, and when I tested BRCA+, that made it real easy to decide to do it.

So far it has been 3 months since my surgery and other than some light hot flashes, nothing too bad. The hot flashes were actually significantly worse on chemo than after the removal. Weird!

As my oncologist says, I am taking the "kitchen sink", with Herceptin and Arimidex to cover all bases. I just pray it keeps the monster at bay!

Natalie

[panicked911]

I was initially given tamoxifen by my surgeon right after my lumpectomy on 10/5 - I am a triple positive 80% er; 70% pr and her2. when I finally saw the oncologist and started herceptain just after thanksgiving - was switched off once we knew lupron shots were working- I was reallt bummed to go off- fel great on that drg - my breast decreased 1/2 a cup size and were muchkess dense - my energy level was way up and th muslce aches ad pains were gone - I was told the AI offered much greater protection against a reoccurance hence arimidex. Would lover to go back on tamoxifen but onc says no - jury is still out - and I am not willing to take the chance

[sassy]

I was triple positive and premeno until chemo put me in chemopause. Have been taking Lupron shots to keep me there so that I can take arimidex. Was told from the very begining this would be the best course of action for me. Surgeon was oposed to having ovaries out for a number of good reasons which has shown to be a wise decision on his part since mast surgery. Hot flashes almost all gone, estradoil (sp) levels exactly where they want them. Side effects from Arimidex, stiff joints very bad in morning and each time I get inactive. Get better when I get up and move. Seems to be getting better and hopefully will go away all together. Others have told me it does eventually go away. So I have hope I won't continue looking like my teenage sons grandmother instead of their mother!

Sassy

[saleboat]

This is such a confusing subject, and I've been to three different Oncs for their recommendation-- (and mused about the different alternatives on this board as well.) All three Oncs have recommended Tamox-- I sure hope it is doing its job. I was ER+ (95%) and PR+ (90%) and am still very pre-menopausal.

For those who are on Tamox, here is a link to a study that was recently done. I am getting a second opinion on this to see if this might be relevant to me. My main Onc hasn't heard of it and doesn't seem that interested in it, but it has been gnawing at me.

http://www.eurekalert.org/pub_releas...-mcr121405.php

Jen

[lisahammo]

I was not Her 2+ when first diagnosed, and was put on Tamoxifan. When I had my recurrence, I was Her 2+, and my oestrogen levels had gone up, so I was taken off Tamoxifan immediately.

Lisa

[R.B.]

There have been quite a number of posts on the subject.

You can search by clicking on search above on the purple bar and entering the term you are searching for.

There is link to a trial which suggests tamoxifen might be counter productive for certain groups.

There is another suggesting concerns fro those with a particular gene.

If you find anything of interest you can always print it and show it to your onc.

RB

[Chelee]

Alaska Angel, This IS a very interesting thread to me. Especially since its time I start on Tamox or femera? (sp) One thing your brought up that I think is really important...is if our medical providers are taking the time to talk to use about it? Mine hasn't yet...but I will be bringing it up to her soon. I want to discuss this issue a bit with her before I just take whats handed to me.

I know several months back when I was still doing chemo, my onc mentioned real quick to me that once I was done with chemo I would be starting Femera. I just said "OK". I didn't even know what it was for at that time?

But NOW I am done with chemo...so this is a topic I am so interested in. My onc wants to put me on the femera as I mentioned...but I had went to a 2nd opinion at a larger cancer center a couple weeks ago...to discuss what has been done and what they think I should do at this point?

They have been there over 30 years...much longer then where I am at now. That place is all about cancer. What makes it hard is my current oco doctor says femera for me...and the OTHER cancer center with the 30 years plus says the one thing they WOULD change in my treatment plan is they REALLY feel I was pre-meno until I was PUT into chemo pause. (Which I agree.) So their choice would be Tamoxifen for me.

She said the Femera is really for post-menopausal women. So NOW I am confused and don't know WHICH one I should take? Thats why I LOVE this thread and anything on this topic. As some know I am stage IIIA, Er & Pr positive, her2/neu 3+++...positive nodes. So I WANT the best drug I can get to stop any recurrances. This is a very important issue I must decide on soon.

I found it also interesting that the way you understand it is that tamoxifen works less then 50% of the time in bc....not just her2. I didn't know that either...thanks for the info. That makes it even MORE important to read up on all of this.

Astrid, I also found your post VERY interesting also! Thanks for taking the time to go over what was said at that lecture and explaining it so well to us. Especially since my 2nd opinion onc at the other cancer center said I should be taking Tamoxifen. Decisions, decisions!

As Saleboat said, such a confusing subject. I agree!

Either way...great thread!

chelee