Tamoxifen and Her2

mmm5

Ladies

I have spoken to many about this but would appreciate feedback, especially from long term survivors of Her2.

My Onc's (both) don't like tamoxifen with HER2 they say there is some data that shows Tamox can accelerate the growth of Her2 cells. I am on chemo induced Menopause with close watch of Hormone levels (age 43) and tried Arimidex and could not tolerate now on Femara for 2 months and the Horrible side effects are kicking in! I HATE THIS MEDICATION

How many of you Her 2 gals are on Tamox, what have you heard and how are SE's as compared to AI's?

kristen8594

Hello,

I was on tamox for 5 years, just ended it and was suppose to go on femara but suddenly my chemo induced menopause suddenly turned pre-menopausal so now I am not on anything!  My onc did not mention anything like yours did about tamox and her2????? I am now 48 but was 42 when I got dx.

For some reason my onc decided to try me on herceptin now 5 years post chemo??? I guess she just wanted to have me on something until we decide if I should have my ovaries removed so I can go on the femara.  But right no I am on every three weeks herceptin for a year.  I know its strange!!!!!

Kristen

u2fan7

 Hi.  I just started tamoxifen one week ago.  I am her2+ but chose to not do chemo/herceptin as my invasive focus was only 2MM and I was told by 2 different oncologists that even though the latest research suggests any size tumor should be treated with chemo/herceptin, that there is still much disagreement over whether women with tumors smaller than 5MM be treated. When I asked my onc what he would reccomend if it was his wife in my shoes, he said "I would have to talk to her about it".  I felt that if he really felt strongly that I should do it he would have said so.  I know I may be taking a risk but I'm hoping the tamoxifen will help.  Neither one of the oncs I saw said tamoxifen was useless for her2+ cases but the one I went to for a 2nd opinion told me he felt my recurrence risk on just doing tamoxifen was 10-15% as compared to  5-10% for doing chemo/herceptin.  I know that 10-15% sounds like a lot and a lot of women would choose the chemo to be more aggressive but I tried to look at the percentages backwards and tell myself that I have 85-90% chance of the cancer not recurring.  No matter what decision any of us make there is always going to be uncertainty and worry.  Believe me, I worry every day but I am praying that I will get through this and lead a long, happy life.  I really respect all of you women out there who have been going through various treatments.  We are all part of a sisterhood and we need to try to stay as positive as humanly possible for what we are going through.

lexislove

mmm5..

I asked my onc this very same question. He says there is not enough evidence out there to say otherwise. He has seen no problems with his patients who have taken Tamox and were Her2. This just may all be specalation or may not. That said, it will be a while before anything is found out.

I am on Tamoxifen and tolerate it very, very well. I have no problems and consider myself lucky. I am scared though about taking an AI. I have heard the side effects can be horrid and Femara with the  thinning hair..ugh! My plan is to stay on the Tamox for as long as I can. I am planning on having an ooph but will remain on the Tamox for the 5 years and then switch to an AI. I hope by then some research has come out saying Tamox longer than 5 yrs is ok...I'm trying to avoid taking an AI at all costs.

orange1

Paraphrase of what my onc at Mayo told me:

Tamoxifen is a prodrug.  In most women it is metabolized to the estrogen antagonist (blocker) endoxifen, which is the bc cancer fighting compound.

In extensive metabolizers, Tamoxifen is just as good or better than AI, even for Her2+ bc.  This is because endoxifen is such a good estrogen blocker, it overcomes any agonist activity (activation of estrogen receptors) that any unmetabolized tamoxifen may cause.  In poor metabolizers, tamoxifen may in fact fuel bc (because the potent estrogen blocker endoxifen is not formed in substancial amounts).  Poor metabolizers that are Her2+ tend to have much worse outcomes on tamoxifen and should be prescribed an AI. 

helena67

That is kind of what I heard too - that the poor metabolizer issue (which affects, for example, about 7% of Caucasians) would explain (at least part of) the difference seen between tamoxifen and AIs. There may be other factors too (maybe dosing or compliance).  I also worried about the effectiveness of tamoxifen in HER2+ BC. I was told by my Onc that results from various studies and meta-analyses don't indicate that it would not work in the HER2+ patients.

In the end, I ended up with an oophorectomy and aromatase inhibitor, which I tolerate fairly well (knock on wood). I figure I can switch over to tamoxifen after 5 years once they have figured this all out.

Compliance is probably the most important issue. If you don't tolerate it, you don't take it or start messing with the dosing....

AlaskaAngel

Hi,

I was dx'd in early 2002 when the trastuzumab trial results were not available, so I never had it. I finished chemo and rads and then my onc put me on tamoxifen. I was on it 1 3/4 years before I learned that tamoxifen could be hazardous for some HER2's. As early as 1998 this has been considered. (Google AIB1 and tamoxifen). My PCP and onc took me off tamoxifen when I brought them the info about it, "because by now you are probably menopausal anyway, and you can take an AI instead".

AlaskaAngel

orange1

Helena67 is right - the results of the adjuvant studies in Her2+ are the best indicator of weather tamox is generally effective inHer2+  hormone receptor positive(HR+)  women.  Her2+, HR+ women typically due quite well. Figure 50% are premenopausal and are therefore getting tamox.  Also a certain percent of post-menopausal also getting tamox.

With CYP screening for metabolizer status, the statistics should get even better. 

Mona-Me

I can relate to your sitution as I am facing the decision of having the Chemo/Herceptin treatment.  The medical oncologist strongly recommends this treatment regimen and my radiaiton oncologist agrees with her.  I am at a loss as to which way I am going to go; originally it was going to be radiation/tamoxifen, but then they got the FISH reading back; so now they have sent out for an ONCO/DX (spelling?) and I am in limbo for two more weeks.  I am truly scared about all of this and know that whatever decision I make has to be the right decision for me.  Thank you and God Bless.

u2fan7

 Orange1,  Can you explain what you meant when you  said  "In poor metabolizers, tamoxifen may in fact fuel bc......"  Is there a way to know if I have poor metabolizers.  I just started tamoxifen last week and I am Her2+ but the 2 different oncs I saw never mentioned anything about poor metabolizers.

mmm5

Alaska Angel so good to hear from you again, I know you have looked at the data and have some good knowledge. I know you discontinued Tamoxifen did you do anything else to limit estrogen in addition to your proper BMI and exercise? I am beginning to wonder in HER2 cases where Herceptin has shown to be so beneficial if that is enough, in addition I am on the bisphos trial. I was low on the estrogen scale only 16% but very high in Her2, low in Ki-67. My Onc states of course Hercpetin was key for me but also 16% is still a positive result for estrogen and wants me to keep on AI.

Thanks for sharing your thoughts, it is nice to hear from a long term survivor.

noellech

Hi mmm5, I am on tamox since Jan, -I did chemo/herceptin for 5 mm tumor. Lots and lots of hot flashes and mood swings on tamox but a small dose of effexor has evened that all out. Tamox is very doable for me and I am glad to have a little extra estrogen for heart and bones. I am not looking forward to AI.

orange1

Hi U2fan7 - I'll PM you with my phone number.  I typed up a long response and lost it before I could post it.  I'll post publicly later in case others are interested, but I'm crazy busy right now so probably won't get to it before the weekend.

Jackie

AlaskaAngel

Hi mmm5,

If one is postmenopausal an AI would be good (although I chose not to take one).

I don't know how to advise you because of your ER+ level of 16%. (I am highly ER+ and highly PR+.) I am taking the risk of being more dependent upon daily exercise, working toward maintaining a normal BMI (right now I am just above my proper BMI by one point), eating a diet that is as much organic as I can buy here, balancing omega-3 and omega-6 fats, and eating primarily grains, fruits, and vegetables, and avoiding simple carbs. I don't smoke or use alcohol or use caffeine (other than what is in organic dark chocolate). I use Stevia for sweetening things. Even with limiting the diet to such healthy foods I struggle constantly to avoid weight gain, due to slower metabolism of menopause. Although it is considered controversial for ER+'s to eat flaxseed, I use 1 1/2 tablespoons of fresh-ground flaxseed a day to help in balancing fats. I do not eat any form of meat or eggs or dairy products that are not organic, primarily because of the commercially-fed hormonal content but also because of the pesticides and herbicides and antibiotics they are given.

MANY of my family on both sides have had breast cancer, and only one metastasized (and died) over the years, but hers was in the 1950's and it was quite advanced before she was diagnosed. One died of ovarian cancer. Of all of them, I was the only one who did chemotherapy. All the others are fine many years after having had surgery and radiation.

The AIB1 problem with tamoxifen use for 1/3 of the HER2 positives muddles things, in that it is possible that I took the tamoxifen just long enough to benefit from it but not long enough to develop resistance to it. In seeing the first mammogram I had after surgery, radiation, and 3 months of tamoxifen I easily could see that my breast density had pretty much disappeared compared to the very dense breast images on mammograms done prior to any treatment. (Sadly, loss of breast density = sagging breasts, as the density is what holds them upward. They also lost most of their sensuality to touch.) I took the full dose of tamoxifen for the first 3/4 year, but after that on my own I reduced the dose by half, and then quit entirely at 1 3/4 years out.

If I were diagnosed today as early stage HER2+++ bc I would not do chemotherapy as I do not believe ER+'s benefit from chemotherapy. I think patients should be honestly told up front that the benefits of chemotherapy are almost nil after 5 years anyway. I would find a way to get trastuzumab plus do the rest of the above. I might do ovarian ablation as well.

AlaskaAngel

Mocity

I am glad I saw this post.  This is something that is bothering me too.  I was dx last Sept with a .4cm tumor and went the agressive route.  I had a bilateral mastectomy and finished chemo(taxol) + Herceptin Jan09.  Now I am taking Herceptin until Oct09.  My Onc is not recommending Tamoxifin because there has been some evidence that Tamox doesn't work as well for HER2+++ women.  So I take Lupron to suppress my periods.  I am 38 years old.  My Onc said some would recommend Lupron and some would say Tamox.  I guess like all the rest of this "crap" it is another decision.  I wish I knew the right now.  But so far Lupron is suppressing my periods which is causing the estrogen to be cut out.

drsfelix

there are studies showing development of tamoxifen resistance in HER2 pos patients.

Like :

Mechanisms of Tamoxifen Resistance: Increased Estrogen Receptor-HER2/neu Cross-Talk in ER/HER2–Positive Breast Cancer

Jiang Shou Suleiman MassarwehC. Kent Osborne Alan E. Wakeling Simale AliHeidi Weiss Rachel SchiffJNCI: Journal of the National Cancer Institute, Volume 96, Issue 12, 16 June 2004, Pages 926–935, https://doi.org/10.1093/jnci/djh166

There are also concerns that AI would do the same. A study with letrozole showed late resistance.

Cheers