CYP2D6 Test - No longer working

hlya

I just saw my ONC yesterday who joined 2 x conferences at the end of last year, one was organized by JAMA in October 2009 (she also mentioned a "German Group" which I didn't understand),  In the conference,  the CYP2D6 "inventor" - Geotz M from Mayo clinic gave all the audience an update about this test based on 1400 cases.

Then Goetz M gave the 2nd update in December  2009 Conference organized by SABCS,  because they added more cases in this 2 months (the  total became 2880),  and  concluded that there is NO Difference between fast metabolisers and poor metabolisers of Tamoxifen vs recurrence rate. So it means this test failed.

Did anybody else get the same update from your doctor?

TenderIsOurMight

Here is a full disclosure on what Dr.Goetz said at the December 2009 SABCS:

http://www.curetoday.com/index.cfm/fuseaction/article.show/id/2/article_id/1338

 In short he says they are re-evaluating the original data for amount of chemo given, time of recurrence, amongst other and that a full report will follow next year. But he continues to recommend the CYP2D6 test, as well as recommend avoiding strong Tamoxifen inhibitors such as the SSRI's (paxil, zoloft, see article please).

 Tender

Member_of_the_Club

Hm . . . either it worked all along or it didn't ever work.  I would hate to think women put themselves into menopause and switched to an AI on the basis of a test that isn't accurate.

lexislove

Im one of those woman...well not yet!

I ordered the test, tested as a poor metabolizer. Im 32 years old very much pre menopausal. I was planning on meeting with a gynecologist to discuss removing my ovaries.

I really dont know what to think at this point. My onc, still thinks Im benefiting...actually he KNOWS Im still benefiting because since I stopped tamox almost 2 weeks ago my hotflashes are so much less. Im also on Lupron, but have noticed a difference.

Im really not knowing what to think about all this...Im so glad that you did post this, maybe it will give me something more to think about. Since I am on Lupron , I can continue with the Tamox or do Femara. I have a couple of weeks to decide.

I would love to hear some more opinions about this cyp2d6 test...it seems controversial.

lexislove

So based on this article...am I right to assume the cyp2d6 test is only reliable/recommended, to help woman avoid strong Tamox inhibitors?

So us woman who are not taking any other meds beside Tamox, this test wouldnt really be accurate from a recurrence standpoint?

Harley44

...my onc doesn't believe in this test...  he thinks it is unreliable, and from what I just read.... maybe he's right...

Harley  

P.S.  Lexis, I just switched to Femara, and I see you are switching in Feb...   let's keep in touch!!

lexislove

Im really shocked about all this.

Like I mentioned I was 99% sure my ovaries would be coming out in the next couple of months. Ive been posting about my poor metabolizer results and ooph questions for the last month, making myself worry and not sleeping.

I dont know to be happy or mad about all this...seriously what do I do now?

lexislove

Harley...I did plan on switching....now I dont know what to do?!!!!!...lol. I see my onc on the 11th, I guess Ill be bringing this article up with him, I dont think he'll be too surprised.

But if I do switch we will definatly keep in touch!

Harley44

lexis,

I think I would be MAD if  I read this, after worrying all this time about being a 'poor metabolizer'.  My onc works on the premise that if I'm getting hot flashes, then it's working.  ;-)

Good luck with your decision.  I'm hoping that your onc will be able to help you sort all this out.  Please let me know what you decide. 

Hugs

Harley

TenderIsOurMight

I would not disregard ALL of the international literature on the CYP2D6 genetic profiling based on Dr. Goetz' comments that he is re-analyzing his data for variables which may have or have not influenced a retrospective analysis supporting higher recurrence in poor metabolizer.

But, I'm a cautious player by nature, and when a repetitive doubt is raised such as with CYP2D6 Tamoxifen poor metabolizing, it's enough to make me shy away from it when alternatives for ER+ tumor treatment exist. Certainly avoiding mid to strong inhibition of the CYP2D6 pathway is fundamental.

We all recognize that given uncertainty in research (seems to take forever to finalize a result), we tend to say it's a crap shoot with breast cancer. Doing what we can to lessen that crap shoot, even if by changing medicines based on not as yet complete information, but good enough information to an alternative is a step I'm with which I'm comfortable. In addition to the US researchers, there are re-known German researchers who have published widely on CYP2D6 polymorphisms. 

jmho,

Tender

Member_of_the_Club

My takeaway message is the one I've had for some time, though i've been increasingly in the minority.  I've always found the case for avoiding SSRIs more compelling than the case for getting the test.  What do you do with test results when there is no clear science on what they mean?  A lot of women here have found both comfort and power in this test so i no longer post, as I used to, that there is still a lot of controversy about it.  But this gets me somewhat angry because oncologists are telling women to take certain irreversible medical steps, with negative health effects of their own, based on incomplete knowledge.  I realize medicine is an art -- advances are made when folks take risks, but terrible mistakes are made as well.  I guess we don't know which this is, but geez with so many of us fighting for our lives some clarity would be nice.

Harley44

MOTC

I totally agree with you.  I have been posting that we just need to try to avoid the SSRIs...  my onc believes (and I have read in CURE magazine) that even Effexor, is a WEAK inhibitor of Tamoxifen... so my onc told me to stop taking it.  

Thanks...  

Harley

lexislove

Im so confused......

Of course I want to do what is right for me, and I have been agressive with my treatment up to this day. But im aware of the potential health isuues that comes with removing the ovaries. Im worried about them.

Clarity would be nice. I was..still am hoping for some news regarding the SOFT trial. That would help answer a lot of questions regarding to ooph or not.

Like I mentioned above, Im not taking any meds beside Tamox. Well Zometa and Lupron, but those dont interfere with the metabolizing. I would definatly make myself aware of any meds if I was to take regarding cyp2d6 findings.....but the whole BC recurrence thing still seems very much up in the air.

I appreciate everyones input. It helps me sort out stuff...<sigh>

lexislove

Now, Im beginning to understand what my onc told me over a year ago when I first brought up the test.

That my test results might cause me excess anxiety and cause me to make a decision (ooph) that is NOt warranted.

hlya

Lexislove:  Sounds like your onc doesn't believe this test either?  

When did you start to take bone test and Zometa after being put on Tamoxifen + Lupron? 

Harley: May I know what SSRIs and Effexor are? And why are you girls taking them?  I never heard of them though.

AnnNYC

hlya, SSRIs and Effexor are antidepressants.  Many of them are metabolized by the CYP2D6 enzyme.

Member_of_the_Club

I'm on effexor right now and was under the impression that it is safe.  Crap.

Harley44

hyla, I see that someone already posted the answer to your question...  yes they are anti depressants..

MOTC,

Well...  SOME people are saying that quality of life is also very important... so if you need to take an anti depressant, Effexor is one that interferes LEAST....   I had been looking for a safer alternative and my primary care dr. is very concerned about my depression issues.... he has given me so many Rxs for different anti depressants, and I was just too scared to take ANY of them...  he gave me Wellbutrin, but I didn't realize that is also an SSRI...   anywhoo.... in my CURE mag, it is listed as a POTENT inhibitor... so needless to say, I didn't fill that Rx....   my dr. is getting frustrated with me.

Now that I'm on Femara, I am still a bit leary of taking any antidepressants, even though my onc told me that it is ok to take Effexor again.  See... when I went off Effexor, I had alot of trouble, so I just don't want to go thru that again...  I now have TWO Rxs for Effexor, and won't take them to the CVS to get them filled....

MOTC, honestly, I think Effexor will probably be ok...  Here's another thing that may help to put things into perspective:

My primary care dr.'s wife had bc 25 years ago, and she took Wellbutrin, which is a POTENT inhibitor... She is doing JUST FINE....  she was 30 yrs. old at dx....   back then, they didn't have these other antidepressants, and they didn't know about this CYP2D6 thing...

Good luck...

Harley

Member_of_the_Club

I was actually on effexor just after my bc treatment, three years ago, without a problem.  I went off for a few years, went back on and now I'm going to go off the effexor again.  I have a freaky side effect of effexor of drenching night sweats and I can't take it anymore.  My mood issues are actually quite mild and my psych says that my serotonin levels have been replenished and I should be fine with nothing for a few years.  I finish tamoxifen in April, so after that I can take any of these drugs.

ktym

Had one well respected Onc want me to take my ovaries out and go to an AI. Admits to being very aggressive. My current Onc is more conservative and I've been happy sticking with Tamox until we know more.  I do worry about second guessing myself if I ever get ovarian cancer.  My Onc never orders CYP2D6 felt it was too experimental so I never pushed it.  I've had a hard time on the Tamox due to SE's so it sure better be worth it.  I'm not sure its fair to be angry at Onc's for decisions that are made regarding the test.  I've had several women think I was nuts for not pushing for the test, and there are a lot of comments here and threads encouraging other women to get the test and even pushing to get the test and complaining that its not offered unless we ask for it.  I think the Oncs get a fair amount of pressure from us to order it.  Once the info is there it would be hard not to make a decision regarding it.  For me right now I'm thinking ignorance is bliss when it comes to the test. Maybe its just because I don't trust my decision making anymore and have just had enough of having to do it and just want no doctors visits procedures or tests or changes for awhile.

Edited to add: or maybe I feel that way because the last few tests I pushed for came back as normal as I was warned they would be. 

chasinghope

My friend i on effexor and is afraid to come off it, night sweats, moodiness. I heard celexa was ok while taking tamox but then who knows in two years they might come up with another study that says "celexa cancels out tamox" BC is a crap shoot, sucks to hear but it's the truth.

lexislove

hyla,

I started Zometa as a preventative of bone mets and to strngth bones to me being put on the Lupron. I started all at around the same time in July 2008.

Harley,

Yes, my onc wasnt buying the test either. He told me to save my money, and even if it tested out to be poor, wich it did, he would NOT recommend doing an ooph and then AI. He said he would keep me on the Lupron+Tamox...AND my Zometa.Im the one who has insisted on doing the ooph and switching...he doesnt agree...but hes not stopping me.

hyla, I took 37.5mg of Effexor from Jan-July 2009. I stopped it cold turkey. NOTHING. I wonder now if it was even working? When I was on it I felt better, but then stopped because I didnt want to be taking anymore meds..plus I though it was adding to my weight gain....blah!

Member_of_the_Club

37.5 mg of effexor is considered subclinical.  It actually works for me, but for most women its too low a dose to affect mood.

lexislove

Interesting. The 37.5mg seemed to do the trick...for me. I didnt even consider going to a higher dose.

Now back to this cyp2d6 stuff.

Ive been searcing for some more articles, but cant find anything. Im trying to inform myself a bit more.

I was tolerating Tamox fine. Ok, I had joint aches and stiffness, but thats about it. I considered myself lucky. My quality of life was pretty good. I am a bit weary about the AI's, but since testing "poor" I have to do what I have to do.

I am so ...so sick of decisions. I know there are a lot of woman who have done the test and get power from knowing their results. But I feel powerless now...

ktym

lexislove, I'm so sorry you're having such a hard time.  Hugs, don't know what else to do for you, so hugs

TenderIsOurMight

Lexislove, this is long and somewhat tedious, yet if you can at least skim the four page article you might obtain some help in your decision making process. As I read the summary, published around December 17, 2009 and commenting on Goetz and Schroth/Brauth work (see here too:http://jama.ama-assn.org/cgi/content/abstract/302/13/1429) the gist is the CYP2D6 polymorphisms issue with Tamoxifen needs further refinement. There is some retrospective evidence that poor metabolizers may have earlier recurrence, but no conclusive evidence that they have worse overall survival. The conclusions are on the last page (page 4), as well as comments on the ethics of testing are worth noting. I'm sorry you are struggling so, and hope this might help you some. Tender

CYP2D6 Testing in Breast Cancer: Ready for Prime Time?

By Nicole M. Kuderer, MD
Division of Hematology, Oncology and Cellular Therapy

Jeffrey Peppercorn, MD, MPH
Division of Medical Oncology
Duke Comprehensive Cancer Center
Duke University Medical Center
Durham, North Carolina | December 17, 2009

 

http://www.cancernetwork.com/cme/article/10165/1500011?pageNumber=1

Member_of_the_Club

So earlier recurrences that would come anyway?  I'm having trouble making sense of that. If there is something about the aggressiveness of your particular tumor, why would a medication affect timing?  Granted, I don't have a scientific background, but if the poor metabolizers aren't getting the full effect, wouldn't that mean a greater number of recurrences?  

TenderIsOurMight

This is from the abstract:

"Tamoxifen is considered a prodrug, whose efficacy may be dependent on active metabolites, including endoxifen. Patients with reduced CYP2D6 enzymatic activity tend to have lower endoxifen levels, but clinical relevance of reduced endoxifen levels remains to be determined. Several small to moderately sized retrospective studies have suggested an intriguing association between poor metabolizer status and increased disease recurrence. However, these data are limited by sample size and methodologic challenges, including the inability to adjust for major prognostic and confounding factors. Several subsequent studies have failed to find an association or found improved outcomes among reduced CYP2D6 metabolizers. Therefore, current findings are conflicting and should be considered preliminary. Nevertheless, the CYP2D6 test is commercially available, making clinical use possible even as evidence in this area is still evolving. More definitive clinical research is needed before routine CYP2D6 testing can be recommended and considered standard of care."

I think it's the major prognostic (grade 1, nodal status, ki-67) and confounding factors (chemotherapy, radiation therapy) that Goetz spoke of at SABCS, December 2009 (see post on CureToday above). It's just too confounded now, MotC to give straight forward analysis.

At the end of the Duke authors article, it pretty much says more work is needed before a conclusion can be made. 

Tender

lexislove

Tender,

Thanks for posting the article, I will read it and see if I can take anything away from it. Will save it, and probably have to return to it. Im glad that you ladies are available to help me sort out all this good and bad.

TY!

lexislove

Hmmmm...I read that the *4/*4 nulle genes had the worse progosis in regards to over all disease survival. That was my scoring. But still...its inconclusive. <sigh>

Im beginning to think just to have the ooph,  never read another article on cyp2d6 and to never look back.

nene2059

Hey Lexis and all.  Lexis I think we connected on another thread about being poor Tamox metabolizers but it bears repeating that I have walked in your shoes.  I drove myself crazy with the information that I came back a poor metabolizer.  I had only been on Tamoxifen a month and a few weeks I believe when I did the test.  Before the test I was driving myself crazy with the fact that I have taken a low dose SSRI for years and would have to go off of it or live with the thought that I may be "blocking" the Tamox.  I had gotten to the point where I switched to Effexor XR and had made peace that it was the lesser of the blockers.  I scanned the internet for anything that could give me peace of mind.  I guess I did all that for nothing because I did have the test and I did have the information that the test stated I was a poor metabolizer.  I did have the ovaries out and I made that decision quick.  Maybe too quick, maybe not.  I called my docs and let them discuss it at tumor board but ultimately the decision was mine and I made it the same way I made the decision to do chemo before surgery, to do a bilateral mx, with the information that I had at the time.  I cannot regret what I did with the best information that I had at the time.  Like you I am in my 30's and was no where near meno, in fact I had been trying to get pregnant before BC diagnosis came along.  I really have not had many menopause symptoms.  I am still me.  If it helps you to decide my BS told me that ovarian ablation is done on premeno hormone + BC patients (regardless of CYP2D6) to prevent recurrence routinely in other parts of the world.  On the other hand early menopause does have its own issues and problems.  I am on Boniva and starting 2x a year Zometa tomorrow because my bone thining is pretty severe.  No one thinks that it could have happened this quickly after ooph and AI though and I am sure chemo and my other treatments did not help.  The good news is that bone loss is reversible.  I feel good with my decision because I feel like I have done all that I can and I am moving on to what is next.  If it comes back I will make decisions with the information that I have at that time.  Treatment is constantly evolving and there will always be studies and reports to contradict studies and reports. Do not make any decision that you can not live with because these are permanent.  Once you make the decision be at peace with it.  If ooph is too much right now keep suppressing the ovaries and take an AI.  I have a friend that has done that for several years now and she is fine.  I on the other hand had the ooph (complete hyster actually because I did not want to worry about those cancers if the hormones were going to go with the ovaries, my decision) and I am fine. My hubby and I have started the adoption process and I got carded playing the lottery the other night! Hey I figure that at 36 I was diagnosed with BC in BOTH breasts and I was a poor metabolizer..those odds have to give me some good luck as well. Good luck with your decision and you will be fine.