Tamoxifen resistence for ER+, PR+, HER2+

[astrid]

I am contemplating entering a clinical trial to compare ovarian function suppression (by triptorelin, oophorectomy, or ovarian irradiation) in combination with tamoxifen vs ovarian function suppression in combination with exemestane vs tamoxifen alone in patients with endocrine-responsive breast cancer in treating Premenopausal Women with Hormone-Responsive Breast Cancer.

I am 48 years old and still Premenopausal. I am ER+, PR+ and HER2+ (3.4). That combination is only about 15-20% of all breast cancers. The clinical trial does not specifically deal with the HER2+ aspect of my cancer. Susan Loves breast book says that tamoxifen is not very effective with HER2+ cancers, so I did some web research and have seen the following: The tumors most resistant to tamoxifen are those that contain not only estrogen receptors but also an overabundance of another growth factor receptor called HER2/neu and a molecule that activates the estrogen receptor called AIB1. Other studies suggest that some estrogen receptors may be located in the membrane, close to HER-2. “Tamoxifen binds to the estrogen receptor in those cells and instead of antagonizing it, it activates it. It acts like estrogen”.

I am scared to start tamoxifen alone because of what I read above and I am not aware of long term treatment for Premenopausal women other then tamoxifen. I am also scared of ovarian function suppression because my husband and I still have great sex and I do not want my drive to be decreased. What do I do?? Go for the trial and leave the decision to fate or the lord? Do nothing and risk reoccurrence?? Do the standard treatment and risk a reoccurrence??

My sister died of BC at 40 and my grandmother died of BC at 53. I want live long then both of them. My sister died before they tested for HER2 and I would bet that both my sister and grandmother were ER+, PR+ and HER2+

[Cathya]

Astrid;

At 48 I am somewhat surprised that your onc has not suggested taking something to put you into menopause so you can go on arimidex. My understanding is that tubular bc (vs ductal for instance) in particularly has a tendancy to spread to the ovaries.....at least this is what a friend of mine told me. She is 42 and had a hysterectomy for that reason. I am sure others will have more ideas.....I was post meno so am on arimidex.

Cathy

[panicked911]

I like you am alos her2 er and pr+ and was premenapausal as well ( 43 when diagnoised) after much debate, research and conferring with 4 differet oncologist in New York ( 2 at Sloan kettering) I decided to go for ovarian supprssion ( via lupron injections) and arimidex. From what I have read and been told the jury is still out on whether tamoxifen works as effectively on Her2 er+ as arimidex, femera etc. For all of us premenapausals the conservative route is the arimidex at least in the inital 3-5 years when the chance of reoccurrance is at its highest. 5 years from now the oncs say this question should be sorted out.
I have been on this combo plus herceptain since November and I can tell you while I have other side effects from all of these meds (aches pains, exacerbation of sinus issues, lack of energy the list of minor annoyances goes on ) lack of libido is not one of them due to all of the meds. Also if given the choice between herceptain weekly or once every three, for me, the once every three has been easier to tolerate. If you go thru radiation, you must have the herceptain weekly during the seven weeks during and three weeks after.

Hope this helps - YOU WILL GET THRU THIS !!!

Susanne

[AlaskaAngel]

I wonder just how far out each of you are from surgery?

I know this post will be long; my apologies.

I am HER2+++, ER+ 50%, PR+ 95%. Like you, Astrid, I have a BIG family history--on both sides for me. I will digress briefly here about that.

A month ago, because of the aunt who had ovarian cancer, I finally caved in and was tested for BRCA 1 and 2, and tested entirely negative. Another aunt died of bc mets to the brain in the early 1960's and perhaps she too was HER2+++. I bring up BRCA testing in the event that you contemplate that as a way of helping you make a decision. After seeing the recent article noting that commercial testing for BRCA 1 and 2 has a significant likelihood of inaccuracy for some who are BRCA 1 and 2, I'm put out that the genetics counselor and the oncologist I saw who specialized in genetics either weren't aware of it or didn't feel I needed to know. To begin with, as I understand it, the number of HER2+++'s who test positive for either BRCA 1 or 2 is much, much smaller than the number for the general population of BC. Secondly, as I understand it, very few BRCA1's are ER+. Frankly, given the recent report about inaccuracy by testing in the USA, I feel that I should not have been encouraged to bother with that test and I am sorry that I and my insurance company are being burdened with paying for it. I don't feel I have any helpful information to go on, nor was I likely to get it from the BRCA testing that I received.

At surgery I was 51 and still quite premenopausal. Because I was stage 1 and my tumor was less than 2 cm but node-negative I wasn't eligible for the Herceptin trial. Oncologists have prevented me from having documented evidence one way or the other whether I should do Herceptin or not. Thank you, ASCO, for that lack of information for those like me.

At diagnosis I learned that European studies were indicating that possibly ovarian suppression or removal (plus rads for local control) plus tamoxifen might be equal to chemotherapy, rads and tamoxifen, and asked my onc about it. Even though I would only benefit from chemo by a tiny percentage, he favored chemo. There was no counseling about the traumatic effects of loss of libido whatsoever. His notion of "discussing the options" with me was to say "you will probably go through menopause". There was no discussion at all with me about the percentage of benefit with chemotherapy. I cannot describe what that loss has meant to me or how violated I feel about his complete failure to provide the genuine opportunity for true patient consent.

If that clinical trial had been offered when I was considering treatment I would jump at it no matter which arm I ended up in. Women need better answers.

At completion of chemo and rads my onc recommended tamoxifen. I specifically said that I had heard that it caused dryness. He laughed at me and said it did not. Again I tried to put trust in his wisdom. Within 2 weeks I was painfully dry and had loss of libido. That has never changed since then. I went to my PCP to discuss it and he had nothing to say. I went to my onc and he recommended the E-string. I use the E-string PLUS lots of lubrication, not for any sexual enjoyment whatsoever because there is none. I use it because it makes sex possible at all, in behalf of my spouse's needs, even if it is still rather painful.

I believe that for those who are younger, the effect of tamoxifen is gentler even for loss of libido, but conversely I would guess that also means their risk remains higher even with tamoxifen. And in trying to advise you, I have to also speculate that even if the transition to menopause is gentler for you, I can't tell whether you would end up losing much libido, or whether that would happen sooner by virtue of doing tamoxifen and/or ovarian removal, etc.

In regard to the Estring... For me there is no alternative. "Petting" and "caring touches" at 55 without entry for my spouse is like a life sentence. I read about the study in England (with a very small group) that indicated that using that kind of estrogen supplementation may very well be counterproductive for those using an AI. My personal experience indicates that could be true. The Estring is changed every 3 months, and if I happen to forget to replace it right away, my eyes are drier, my skin is drier, and I start having hot flashes again. What does that tell you?

I genuinely believe in actively participating in the search for better answers. That is why I chose to be a participant in the clinical trial using testosterone for breast cancer patients, even though being HER2+++ might increase my risk for recurrence. If they do not test using patients who are HER2+++ then there would be no evidence applicable to HER2+++ patients one way or the other. To be in that trial I had to pay my way and fly to a participating site in the Lower 48. It is just too easy for those who offer life-saving therapy not to place any significant value on our libido.

I have also read about the problem for those who are both AIB1 and HER2+++. Please note that neither my PCP nor my onc had the organizational skills and/or openness to bring that up with me for MY consideration. I had to take the question to THEM. (But then, neither of them ever even told me that I was HER2 positive in the first place, so the vacuum of their value in providing information to me is not a new trend for them.) By that time I had been on tamoxifen for 1 3/4 years. They did not even acknowledge the question. They merely responded that since by this time I was menopausal, it was "okay" if I wanted to switch to Arimidex. I had read that perhaps Femara was more effective, but the recommendation was Arimidex.

So currently I am recommended to take Arimidex--which likely isn't working because of the Estring--and causes additional loss of bone density on top of all that is lost through chemotherapy.

You would think that there would be at least enough professionalism that researchers would pause at least briefly in their stampede for greater knowledge to try to actually find a way to apply it, and that when they test for HER2 they would find a way to test for AIB1 instead of hiding it from us and leaving all of us to try to figure out how to deal with it.

I happen to believe that my PCP literally is doing the very best he can. My onc is extremely well-liked and respected by and large by both patients and professionals. On the other hand, I don't and won't accept that patients like me are particularly unable or "difficult" to be a partner in our treatment, either.

I don't know if my thoughts and experience are helpful to you, but there they are.

With sincere sympathy,

AlaskaAngel

[R.B.]

You might want to look at past posts using the search engine click on search above. Tamoxifen oestrogen cyclin D1 fertility etc. are terms you might want to try singly in pairs etc. Do check out the Tamoxifen side effects by searching on google or similar.

You might also like to look at the posts on omega three and six oils, and the wider subject of diet if this is not an area you have thought about as an adjunct. There are a lot of trials suggesting diet and exercise can moderate risk.

Practice and opinions are beginging to shift into new areas, pre testing for risk status, the possibility of targeted therapy without chemo, etc

It is not easy to find stats for outcomes for premenopausal women.

"CancerLynx" and "AnneAppleseed" are two sites maintained by women with attitude that I have found contain interesting reading.

Alaska Angel is not alone in expressing frustration with the level of pre-treatment information. Research on AnnieAppleseed suggests that premeopausal women are the group least satisfied with treatment. Lack of education on potential treatment impacts are reported as not uncommon.

I am male and not a sufferer, but what I have read does suggest to me that it is important for those who have the time and are feeling up to it to read as much as they can on their treatment options so they can ask the questions they need to. These must be very personal choices as the disease itself is essentially individual.

Lots of reading may help you be more certain in whatever decision you finally take in conjunction with your advisors.

RB

[Susan2]

I share your frustration. I was diagnosed 6+ years ago triple positive premenopausal. After going through chemo-induced menopause, I started on Tamoxifen (at that time, nothing else was available). After just a few months on Tamoxifen, I came out of menopause and have stayed out. At one month shy of 5 years on Tamoxifen, I recurred. At that point, my dr.'s first inclination was to start Lupron and use an AI with Herceptin to fight it. However, the tumor history had changed and was now ER-.

My overall experience with Tamoxifen was good (not great, but not terrible). The side effects for me were manageable. And I believe it helped delay the recurrence.

The drs. first thoughts are to stop the disease and QofL issues are secondary. While we all agree that this is paramount, as more of us become longer term survivors, QofL becomes more and more important. This will be a more reeducation process for the drs. As we all educate ourselves about the various possibilities, we can help educate the drs. about helping preserve our QofL - because we ARE going to be here a long time.

[Cheryl E]

I was a few months shy of 40 and premenopausal when I was diagnosed 3 years ago. I too was told by 3 drs that because of the ER+. PR+, Her2+ that the best treatment was ovarian suppression and an AI (arimadex or femara). Because we were done having children, I chose to have my ovaries out (very easy). Although my libido has decreased, we still have an active sex life. I believe it's all about positive mind set and communication with your husband. And in defense of drs; my onc and ob/gyn are always concerned and ready to make changes/additions/suggestions if I feel any quality of life issue is at risk, including sex life!

[sassy]

I was diagnosed 2/05 at age 45. Premeno, triple positive, I have been on Lupron to keep me in the chemo induced postmenopausal state. Neither my surgeon nor my onc was in favor of ovary removal if Lupron was an option. Started Arimidex in November following rads. Although some changes have taken place, lubrication has helped.

My husband and I both felt that the optimal course of treatment outweighed possible side effects.

Sassy
________
LIVE SEX