CYP2D6 Test and Tamoxifen

Lolita, thank you so much for your post - you are a godsend.  What would we do without these forums!!  Have a wonderful day.

Big hugs

Helena

Hi All,

I just came across this forum/topic and I am sure glad I did.

I finished radiation May 18, and started the tam May 27.  I sw my med onc May 26, and he most certainly pulled the blood for the CYP test as it is extremely important to know how one metabolizes tamoxifen.  He told me...hope for hot flashes, lots of them.  He told me if slow, well then we need to find another way to systemically treat recurrence of breast cancer (injections or surgery, then an AI).  if fast, a-ok.  if intermediate...hmmmmm

well, as of Monday (it is now Saturday), my right breast, esp the boost area, began to relapse.  I mean...hurt, ache, swell  ugh (I had a real hard time with radiation; docs speculate maybe because I have ulcerative colitis as well?).  Yesterday, I was absolutely miserable.

I pulled out my tam info sheet, and I saw on there as a possible SE radiation "flare" ... called my med onc nurse, she asked others and the rad oncs in her practice ... they all say that is a good thing, the tam must be working.

I called my rad onc nurse in Durham and let her know

 (I had surgery in Raleigh and my med onc is in Raleigh NC (NC Cancer Center, Rex Hospital), but since I live so far away, I had my radiation at Durham Regional, a Duke center, as it is the closest drive for me)

okay...so thru all the calls to and from the med onc, the rad onc, my pain doc, and my gastroenterologist (the oncologists want me to take NSAIDs, my gastro says NO), I find out I am an intermediate from the med onc

So, online I go ... as a retired scientific researcher from big pharma, I have no probs understanding the journals.

My med onc said increasing the dose to 40 mg is not yet accepted by the FDA thus he will not do that, and he said if I were interested, there is a clinical trial there and was I nterested, I said maybe, depends on how often I have to go to Raleigh (an hour drive one way for me)

He said he was encouraged by this flare I was having, will discuss with him later

but ... I am concerned ... why take a drug that is not really going to help me reduce recurrence, and esp if it may increase my chances of recurrence?  It is making me sick to think I have yet another obstacle to cross with indesirable outcomes ...  I want my life back !!!!!

I have been on tam for 1.5 weeks, when should I be getting hot flashes?  My med onc says that is a sign the drug is working.

Again, I have the big questions...I thought I was on the down swing of all of this 

I need to now research this fareston ...but after I go trail riding with my friends

The New York Times did an article on this topic and many of us were interviewed.  If you check this post:  http://community.breastcancer.org/forum/78/topic/726526?page=1#post_1218978

and go about half way down to "yoyolady" (sp??) , She was the one the Times wrote about. As you can see she suffered with horrendous se as I did as well and she found she was getting little benefit from the drug.  So unless something else is going on I personally do not believe that hot flashes = the drug is working as it should.  Some normal metabolizers have few or little se.  I think there is much more to be gleaned from all of this.

 Genelex,,,,,,,,,,,,,what's the bottom line on dosing intermediate metabolizers.  Are we  to increase our Tam or decrease???

warm regards

jan                                                                                                                                 

I had the test done and came back as an Extensive Metaboliser - I have NO side fx - no hot flashes, no joint pain, no night sweats - go figure!!!  My Onc said it was because I am still having regular periods (?) but I feel relieved that the drug is working and more motivated to keep popping it for 4+ more years.

Many thanks from me, too, Kashcraft -- so helpful.  Where did you find these guidelines?  I'd like to show them to my onc.  I tested as an Intermediate Metabolizer but we haven't made any modification to my treatment (I'm on 20mg tam/day) other than keeping an eye on things that might interfere/inhibit the Tam.  I worry whether we should be doing more. 

Thanks again!

I am also an intermediate metabolizer.  It is not as simple as simply increasing your dose of the tamoxifen or other drug that you do not fully metabolize.  For some people the slower metabolization of the drugs means they will have more side effects.  In fact, the company that did my testing, suggests a slightly lower dose of tamoxifen for intermediate metabolizers. And for some of the other drugs on the list,  I have had very bad side effects which appeared to be allergic reactions (codeine is one that I cannot take because I do not metabolize it into morphine and instead I have an allergic reaction to it...that is a drug that requires both CYP2D6 genes and I only have one, hence I am an intermediate metabolizer).  

So based on what I have read,  I don't think we can assume that a higher dose is necessarily better.  My advice (which I realize no one asked for) is that  intermediate metabolizers should completely read the report that came with your results and then have a long conversation with your oncologist about what the next step should be. On one level, it may be confusing. But on the other level, we are so lucky to have this test to help us make decisions.

In reference to the provided dosing guidelines:

These were reviewed by our Medical Director, Dr. Jessica Oesterheld, a recognized expert in cytochromes who co-authored The Manual of Drug Interaction Principles for Medical Practice: The P450 System. They were also reviewed by students on rotation for their final year of PharmD school. These are the same dosing guidelines that would be provided for any CYP2D6 prodrug. Dosing guidelines can be viewed and a pdf downlaoded at http://www.tamoxitest.com/HP_dosage_recommendation.html.

For those that came back as a CYP2D6 IM or PM, please take a look at http://www.genemedrx.com/explainreport.ppt. Your CYP2D6 status affects your ability to process about 25% of medications (the 2D6 substrates at http://www.healthanddna.com/Druglist.pdf are the most common), not just tamoxifen, so be sure all of your healthcare providers know and use this information when prescribing.

BTW- Mandy is right, discuss it with your oncologist. Although from a pure drug-gene perspective an increased dose makes sense for IMs, there are often multiple other factors to consider such as co-medication and side effects.

Good for you Annette! Patients need to become informed and ask their physicians about tamoxifen testing.

You may find this article of interest -  http://jnci.oxfordjournals.org/cgi/content/full/100/9/642. Using data from other studies, they determined that tamoxifen would be as effective as AIs for normal metabolizers (with a lower cost less significant potential side effects), but 5-year recurrence rates would be 1.6X higher in IMs and 2.9X higher in PMs. No studies have been done yet to see if IM recurrence rates would be reduced at higher dosing levels.

I have had no encouragement from my rad oncologist to be tested for the CYP2D6 enzyme. I fit into the criteria for the  'routine' prescription for Tamoxifen. Given all the potential/real SE, I want to make sure this drug will work for me and so I have opted to order the test myself. After researching the options and speaking with a relativre of someone who was tested, I have sent off my buccal swabs to Genelex. I will be covering the cost myself, as I live in Canada and the lab is in the USA (no labs in Canada do this test as far as I know). It took 4 business days for me to get the packet; 3 days for them to get it back (there now); and I have been told I should have the results within 10 business days. My rad finished Sept 2, and my onc wants me on Tamoxifen within 6 weeks. So the clock is ticking!

Thanks, Helena. I am just amazed at the lack of knowledge/interest/support of some oncological doctors. Makes one wonder!

For some reason my onc is fighting this test.  Her physician's assistant said if we do the test, we won't have anything to offer the gals who don't metabolize. My inquiry of why would you give them a drug with side effects and little or no benefit was not answered If I am an optimist, perhaps they hope there will be some small benefit.  But they should let that be up to the patient who is a non metabolizer.   So I had to organize the test myself.  I wonder how many others have had to organize (and pay for) the test themselves.

Can't believe they would give you "no options if you can't metabolize" .  A woman has a right to be informed whether there is any benefit or significantly diminished benefit.  As well, as we all know, there is an option and that should be presented to the client.

We are advised by my wife's oncologist at Mayo Clinic Rochester that they consider tamoxifen treatment to be a reasonable choice for an intermediate metabolizer.  Their concern is poor metabolizers.  They also do not perform endoxifen testing.  Thought I would share this with you, as we wrote the Doctor and he was kind enough to share his opinion on the subject with us.  He also advised that an aromatase inhibitor is not recommended in a premenopausal woman whose periods have stopped as a result of chemopause.  He says ovarian function has been known to return up to 5 years later.

Thanks, Timothy. After all I've read and in discussion with my rad onc (who is MUCH improved!), I have decided to take the tamoxifen at 1 1/2x the reg dose. I also am very conscious of the things that will inhibit the tamox's metabolization and am consciously avoiding them.

(BTW - I am post menopausal)

2 pills down of a possible 1,825 and so far so good!

Have a great w/end everyone. 

Thanks so much for this, Kristine. Maybe someday sooner than later, I will be able to convince my onc and others around him, the importance of this test!  Have a great day.