Tamoxifen not beneficial for HER2 +

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Janeluvsdogs
Janeluvsdogs Member Posts: 242
edited June 2014 in Complementary and Holistic Medicine and Treatment

Five of six studies so far have shown that treating patients who are HER2 positive with adjuvant Tam does not have a beneficial effect, and Bianco et al.[37] have even reported a detrimental effect.

http://www.medscape.com/viewarticle/407813_5

Does HER2 Overexpression Predict Adjuvant Tamoxifen Failure in Patients With Breast Cancer?

Tamoxifen (Tam) acts through the oestrogen receptor(ER) pathway and since it is a drug that has proven to reduce relapse, death rates and risk of contralateral breast cancer, the reason for Tam failure is an area that generates intense research. Both experimental and clinical evidence have indicated that the HER2 pathway interacts with the ER pathway.Experimental evidence has shown that oestrogen-dependent MCF7 cells that over express HER2 are rendered tamoxifen resistant and have reduced numbers of ER[29,30]. Hence HER2 pathway has been investigated for contribution towards development of Tam resistance and HER2 has been proposed as a potential marker of Tam sensitivity. Many clinical studies have found an association between HER2 OVEREXPRESSION and Tam failure, and recently a metaanalysis of seven studies[31] concluded that metastatic breast cancer over expressing HER2 was resistant to Tam (odds ratio of disease progression was 2.46).However, it remains controversial as to whether adjuvant Tam has beneficial or detrimental effects in early breast cancer (EBC) over expressing HER2[32-37].

Five of six studies so far have shown that treating patients who are HER2 positive with adjuvant Tam does not have a beneficial effect, and Bianco et al.[37] have even reported a detrimental effect. Only the study by Muss et al.[36] concluded that HER2 status did not influence the outcome of patients treated by Tam.Among patients receiving adjuvant Tam, combined analysis[38] of studies with analysable data[32-34,36,37] and using the number of patients and the length of median follow up as a weighting factor for the relative risk(RR) of relapse or death per study reveals that HER2 over expression increases the risk of relapse/death by 75% (RR = 1.75). Such results strongly suggest that over expression of HER2 predicts reduced response to adjuvant tamoxifen in patients with EBC, but does not exclude benefit in patients with HER2 and ER/PgR-positive tumours. However, caution should be exercised when interpreting these results. All of these studies were retrospective and there was no standard methodology or cut off for the evaluation of HER2 expression

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  • HopingforaCure
    HopingforaCure Member Posts: 163
    edited August 2010

    I'm so confused!!!  You read one study that says one thing and another that says something else.  Not to mention the fact that I don't understand all the scientific jargon.  I am seeing my oncologist next week for my 6 month check up.  I will print out the medscape article above to see what he says (I'm on tamoxifen and took herceptin for a year). 

    Anyway, just ran across this which is why I'm confused....

    http://clincancerres.aacrjournals.org/content/10/4/1409.full

    "Conclusions: The combination of tamoxifen and Herceptin is formally demonstrated to result in synergistic growth inhibition and enhancement of G0-G1 cell cycle accumulation. In vitro, the individual drugs or combination produces a cytostatic effect. These results suggest that combined inhibition of ER and HER-2/neu signaling may represent a powerful approach to the treatment of breast cancer."

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  • Mountains1day
    Mountains1day Member Posts: 102
    edited August 2010

    Hopingforacure, 

    I have found another informative site for the HER2positive gals at:  HER2Support.org   Check it out! 

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  • mmm5
    mmm5 Member Posts: 1,470
    edited August 2010

    Hi Ladies

    I have an ONC that quotes these studies all the time, he is very renown ONC that is highly respected at U of A and came from MD Anderson. He will not agree to tamox in Her2 gals in any instance. I have had 3 ONC's all very respected and they all tell me to go with what he says because he is so highly respected. (yet they sometimes give tamox to HER2 pts)

    I argued with him many times about it as I was suffering so from OVARIAN suppression and Femara, but now 2 1/2 years later am happy I have followed his advice. However I will say I know many gals Her2 that take Tamox and have been doing fine for several years.

    Sometimes all of this is very confusing, I think the best thing to do is research get several opinions and then do what feel right for you and your intuition and following this advice has served me well. (knock on wood) 

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  • mmm5
    mmm5 Member Posts: 1,470
    edited August 2010

    FYI...this same Onc is ok with me going off of ovarian suppression at the end of this year and actually said to me today that a little extra estrogen would not hurt me.

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  • Member_of_the_Club
    Member_of_the_Club Member Posts: 3,646
    edited August 2010

    I have also read that tamoxifen is less effective in women with her2neu overexpression.  I didn't look into it further because I'm not her2neu positive, but i do think women who are should discuss this with their oncs.  

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  • REKoz
    REKoz Member Posts: 590
    edited August 2010

    Well, what does one who is 90% ER pos (same % PR as well) do when they cannot tolerate AL's?  My Onc. (who is also very well respected and known in these parts) had me try Tamox after Arimidex and Aromasin just about crippled me. I've now been on Tamox. since Feb and have tolerated this much better.  I HATE reading stuff like this because my only other alternative is nothing......

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  • Member_of_the_Club
    Member_of_the_Club Member Posts: 3,646
    edited August 2010

    Rek, I think you go with your onc's recommendation.  His expertise trumps ours.  You could ask him about this for peace of mind, and my guess is he will reassure you.  You have to go with the better quality of life.

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  • orange1
    orange1 Member Posts: 930
    edited August 2010
    From HER2 to Herceptin: Does HER2 Overexpression Predict Adjuvant Tamoxifen Failure in Patients With Breast Cancer?Pharmacist Rating: 0 stars  ( 0 Votes )           Rate This Article:      Print This Print ThisEmail This Email this  SummaryHER2 Structure and FunctionHER2 and Breast CancerDetermination of HER2 Amplification and ExpressionDoes HER2 Overexpression Predict Adjuvant Tamoxifen Failure in Patients With Breast Cancer?HER2 Expression and Response to ChemotherapyHerceptinContra-indications to TreatmentFuture UsesReferencesDoes HER2 Overexpression Predict Adjuvant Tamoxifen Failure in Patients With Breast Cancer?Tamoxifen (Tam) acts through the oestrogen receptor(ER) pathway and since it is a drug that has proven to reduce relapse, death rates and risk of contralateral breast cancer, the reason for Tam failure is an area that generates intense research. Both experimental and clinical evidence have indicated that the HER2 pathway interacts with the ER pathway.Experimental evidence has shown that oestrogen-dependent MCF7 cells that over express HER2 are rendered tamoxifen resistant and have reduced numbers of ER[29,30]. Hence HER2 pathway has been investigated for contribution towards development of Tam resistance and HER2 has been proposed as a potential marker of Tam sensitivity. Many clinical studies have found an association between HER2 OVEREXPRESSION and Tam failure, and recently a metaanalysis of seven studies[31] concluded that metastatic breast cancer over expressing HER2 was resistant to Tam (odds ratio of disease progression was 2.46).However, it remains controversial as to whether adjuvant Tam has beneficial or detrimental effects in early breast cancer (EBC) over expressing HER2[32-37].Five of six studies so far have shown that treating patients who are HER2 positive with adjuvant Tam does not have a beneficial effect, and Bianco et al.[37] have even reported a detrimental effect. Only the study by Muss et al.[36] concluded that HER2 status did not influence the outcome of patients treated by Tam.Among patients receiving adjuvant Tam, combined analysis[38] of studies with analysable data[32-34,36,37] and using the number of patients and the length of median follow up as a weighting factor for the relative risk(RR) of relapse or death per study reveals that HER2 over expression increases the risk of relapse/death by 75% (RR = 1.75). Such results strongly suggest that over expression of HER2 predicts reduced response to adjuvant tamoxifen in patients with EBC, but does not exclude benefit in patients with HER2 and ER/PgR-positive tumours. However, caution should be exercised when interpreting these results. All of these studies were retrospective and there was no standard methodology or cut off for the evaluation of HER2 expression. Furthermore, the ER and PgR status was not known in all cases. The first three studies[32-34] analysed subsets, consisting of small numbers, of non-randomised patients with breast cancer, thus raising the possibility of a bias in the selection of patients for the treatment of control groups. These three studies[32-34] were also poorly designed as there was no objective from the outset and multivariant analyses were not always performed.Data drawn from the latter three studies[35-37] should be more robust. The latter three studies consisted of subsets of patients who were randomised totamoxifen or no treatment. The number of patients was also larger and the studies also had a better design as there was an objective from the start. However,they were all published in abstract forms with insufficient details to allow proper meta-analysis that can more accurately determine the overall hazard ratio with the relevant 95% confidence interval.In a small study (n  11) Dowsett et al.[39] have recently reported significant anti-proliferative activity of hormonal therapy in patients with tumours over expressing HER2.At present the data is not probably strong enough to change clinical practice. The ideal study would be a randomised prospective controlled trial assigning patients with quantified HER2 expression totamoxifen, chemotherapy or no treatment groups.However, such a proposed study is impractical. A quick feasible solution would be to perform a metaanalysis on the above trials. Another option is to perform a retrospective analysis on a large number of patients who have been randomised to either tamoxifen or no treatment in previous trials to be followed by a subsequent meta-analysis. The level of HER2, ER and Pgr should be determined by standard and universally accepted methods. 
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  • orange1
    orange1 Member Posts: 930
    edited August 2010

    Above is the entire article.  Jane left part of it off.  It does not conclude that tamox doesn't work for Her2+.  It asks the question and discusses some studies noting significant issues with most of them. 

    The article that Jane posted was published in 2001, before the large Herceptin trials were done.   

    There were 3 large adjuvant Herceptin studies that have been published so far.  In these trials, the vast majority of premenopausal women that were both HR+ and Her2+ received tamoxifen.  In two of the trials - both HERA and the Joint Analysis trials, they had lower recurrence rates that the HR- (women who did not receive tamoxifen.) In the third large trial, BCIRG 0006, results were not broken out separately for HR+ and HR- women - so there is no way to know if HR+ or HR- did better.  Based on the two trials where we do know the out come of HR+ and HR-, HR+ did better.  So it would seem that minimally tamoxifen did not negatively affect outcome and probably did improve it.  

    Tamoxifen resistance in Her2+ cancer is well known.  This means that in pre-Herceptin days Her2+ women that were also HR+ and took tamox didn't do as well as Her2- HR+ on tamoxifen.  Well no kidding! Her2+ cancer is an especially aggressive cancer.  This is a well known fact to anyone who has been diagnosed with it.  This is old news, much like the article Jane posted. However, it does not mean that tamox doesn't improve outcomes in Her2+ HR+ cancer. 

    In a perfect world, we would know definitively if tamox helps her2+ women or not.  The only way to get this answer is a prospective randomized trial comparing similar Her2+ women, half getting tamox, half not getting it.  So far it hasn't been conducted - likely because the researchers, when they designed the Herceptin trials, couldn't ethically include a no tamox arm because they believe tamox helps. 

    Diagnosis: 8/2007, IDC, 1cm, Stage I, Grade 3, 0/3 nodes, ER+/PR-, HER2+

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  • Janeluvsdogs
    Janeluvsdogs Member Posts: 242
    edited August 2010

    Orange1, I did link to the full article with all the evidence. You must have missed it.

    Thank you for noting that the the one doctor said he did not want to change standard of care in the face of the evidence that Tamox was a not beneficial when mixed with Herceptin in 5 out of 6 studies. And that combining Tamoxifen made things worse in another study.

    The one doctor in his boilerplate caveat concluded he didn't want the evidence to get in the way of what they traditionally did. Most articles end that way. The researchers don't want to make waves so they conclude let's not move too fast to correct the mistakes discovered in new findings.

    Better to wait a few more years and have more women suffer from combining Tamoxifen and Herceptin.

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  • REKoz
    REKoz Member Posts: 590
    edited August 2010

    Can someone explain something to this confused sister?  I thought that Herceptin "targeted" the overexpression of the HER2 gene and for lack of a better word, "fixed" it? Here I was in all my imagery glory, imagining the gene overexpression was stopped dead in it's tracks with every infusion. So while I was HER+ at biopsy, the Herceptin ideally would put that gene back to "normal."  I thought that was the miracle of Herceptin and the reason this drug turned around what was previously a poor diagnosis?

    This thread has caused me to think I've missed the boat as far as how exactly Herceptin works. Otherwise, why would there even be a question about Tamoxifen efficacy on HER2 patients? I am the first to admit that there is nary a one scientific understanding gene within me! So, if someone could explain to me in the most elementary way where my thinking is wrong, I would truly appreciate it. TIA

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  • lago
    lago Member Posts: 17,186
    edited August 2010

    How do they know if you are not responsive Tamoxifen? How do they even know if you respond to Herceptin if you didn't have it before surgery?

    Seriously if  Tamaxifen doesn't work and you are pre/peri menopausal then I would think the more oncologists would be recommending women get their ovaries removed. I too have read the same regarding Tamoxifen but I have also read that aprox. 50% don't respond to Herceptin. If you are that worried about Tamoxifen not working then I would ask about removing your ovaries.

    No one said they would definitely cure us. They are just doing everything they can to try.  Nothing wrong with being informed and asking questions but right now this is the best treatment they have. Some of us live long lives.

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  • Member_of_the_Club
    Member_of_the_Club Member Posts: 3,646
    edited August 2010

    Its obviously much more than one doctor because doctors still prescribe tamoxifen for her2+ patients.  It makes a huge difference that this study is from 2001, before herceptin was used in early stage patients.

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  • Member_of_the_Club
    Member_of_the_Club Member Posts: 3,646
    edited August 2010

    I would add that Jane's mission on these boards is to dissuade all women from taking tamoxifen.  There is no circumstance in which she would say its OK to take this drug, even though it has years of studies showing a benefit.  (I personally know a woman with mets who was stable for 7 or 8 years on tamoxifen -- they could see on the scans that it was working very effectively which is why they kept her on the drug for over 5 years).  Tamoxifen isn't for everyone, obviously.  But since Jane is completely ideological about it, and sees no room for nuance or benefit, I think you have to take her posts with a grain of salt.

    Often on these boards you read women decrying the one size fits all approach that some oncs take.  We want nuance.  We want our own disease and circumstances to be considered.  If you say no to a treatment all the time, no matter what the circumstances, that is a one size fits all approach that negates our individual circumstances and disease.

    Jane never posts about her own disease or why she takes this approach.  We know that she chose to forego tamoxifen, as is her choice.  But if she had DCIS its one thing and if she had a heavily er+, node+ disease its another. 

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  • Janeluvsdogs
    Janeluvsdogs Member Posts: 242
    edited August 2010

    MOC, I report the published evidence. If you want to attack the evidence, please do. But don't shoot the messenger because you don't like the evidence.

    And please, calling evidence you don't like "completely ideological?"

    Please email all the peer-review publishers of the medical articles, The NY Times and The San Antonio Breast Cancer Symposium and tell them they are "completely ideological."

    Maybe you can ask about the medical history of the authors also, since you feel you need to know the medical history of the messenger.

    Also, could you please cite where I ever wrote, "say no to a treatment all the time?"

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  • Member_of_the_Club
    Member_of_the_Club Member Posts: 3,646
    edited August 2010

    OK, Jane, I'll bite.  In what circumstances do you think women should take tamoxifen?

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  • Janeluvsdogs
    Janeluvsdogs Member Posts: 242
    edited August 2010

    MOC, It doesn't matter what I think. It only matters what actual published evidence exists about efficacy, side effects, complications and the reasoning behind Tamoxifen and Arimidex. It is a very individual decision, as you have said.

    You have seen people on these boards say, they aren't interested in evidence. Or that the evidence will scare newbies off so I should stop mentioning it. My personal belief is that there should be full disclosure about the drugs and their survival value. Informed people will make the best decisions and may consider the wealth of other strategies.

    It hope this clarifies that my only "mission" is full disclosure.

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  • Member_of_the_Club
    Member_of_the_Club Member Posts: 3,646
    edited August 2010

    You didn't answer my question so let me rephrase:  Given your view of the evidence (and others have pointed out that you take portions of studies, often out of context, and reject other studies or other portions.  Granted, science often involves some discernment and culling of results, but don't pretend you aren't imposing your own biases on your form of culling, which you present as some kind of objective truth), given your review of the "actual published evidence" when do you think women should take tamoxifen, if ever?

    Simple question.  Do you ever think anyone should take tamoxifen? 

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  • taranebraska
    taranebraska Member Posts: 129
    edited August 2010

    I'm appreciating this "discussion", thanks to everyone who has joined in.  My ONC has said I will take Tamox after I'm done with Taxotere (Docetaxol), Carboplatin and a year on Herceptin, but she'll do a hormone test to see if I'm really pre-menopause or peri-menopause. 

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  • DesignerMom
    DesignerMom Member Posts: 1,464
    edited August 2010
    Member of the Club-  Again, thank you for pointing out what many of us have expoerienced with Jane. She most definitely appears to be totally anti Tamoxifen.  As her posts only involve criticism of Tamoxifen, many of us have asked her direct questions repeatedly.  Rather than answer, she usually disappears.....soon to pop up on yet another thread promoting her anti Tamoxifen agenda.  And by the way, I STILL have not decided whether I will take Tamoxifen, but I certainly think it has a very valid place in BC treatment.
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  • Lady_Madonna
    Lady_Madonna Member Posts: 472
    edited August 2010

    Hmm...looks like the disappearing act struck again!!  And I was really looking forward to the answer.  Well, thank you for this discussion because it is very relevant to my upcoming decisions and I might have let some scare tactics sway me without even realizing it.  Knowledge is power...  FULL knowledge, that is ;)

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  • HopingforaCure
    HopingforaCure Member Posts: 163
    edited August 2010

    Mountains1day--thanks for that website.

    So, I saw my onc last week for my 6 month check up (and all is well--yipee).  Anyway, I didn't take a copy of the study in, but I brought up the topic and we discussed it and he strongly believes that my treatment plan is best for a person in my situation. He wants me on tamoxifen for 5 years and then wants to switch me to an AI.  He's read the info, and he says all the top oncs in the country do prescribe tamoxifen (when appropriate) to HER2+ women.  I also e-mailed a bunch of questions (including this issue) last week to my friend's brother who is an onc at a well respected hospital and he agreed with my onc.

    So, I'm going to keep doing what I'm doing and continue to work on those things I can control--good nutrition and exercise....

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