CYP2D6 Test and Tamoxifen

kira66715

Positive, thanks for the additional information. I did put a call/email into Dana Farber to see when their test will be available for endoxifen, but as you pointed out, it's not the only active metabolite.

I was able to read the article from Clinical Cancer Research--very interesting. Dana Farber said they're not ready to start the testing yet. Hopefully by June. 

Kira 

phoenixrising

I remember reading that.  It's exciting news and I hope they have success in achieving that.

I wonder how using endoxifen directly will decrease the se of tamoxifen.  I thought I was the anti estrogen activity of endoxifen that created the se's.

~ Tender~ Thank you for your above reply to my post.  I still don't get it  but I'm determined to!

~Revkat~ I could be wrong but I'm sure it's decided that 2D6 is the primary route for tamoxifen and others, like 3A4, 2C9  is a secondary route  for what isn't handled by the 2D6 and is much slower.

RubyCA

Well, like so many other issues in breast cancer, it seems as if there is still a lot to be researched and a lot of unknowns. Personally, though, since the blood test found that I am a poor metabolizer of tamoxifen, I have chosen to go into menopause so that I can take an AI.

 Yesterday I  had my first  Lupron shot (not at all painful, as I had feared). My OB/GYN is not convinced that Lupron does as complete a job of suppressing ovarian estrogen as having the ovaries removed, so I am planning to have the surgery in a couple of months.

 This is all very confusing, and I don't think the doctors are really sure about any of it either! But it certainly seems like shutting down estrogen production for estrogen-receptor positive breast cancer is a good thing.

momofbraj

I too was found to be a poor metabolizer of tamoxifen.  I have received two lupron injections and my estrogen levels have not been suppressed enough to start Femara as I had hoped.  I have an appointment with the surgeon to discuss removing my ovaries in two weeks (not soon enough).

becky1955

I had taken the test and was found to be an interemediate metabolizer. My oncologist at that time left it up to me to determine if I wanted to take it or not. She also told me that Tamoxifen  is the only hormonal therapy drug approved by the FDA for women diagnosed with DCIS. I recently changed oncologists. My  new oncologist has recommended Evista, and I found an article that recommends it for those who have a problem with metabolizing Tamoxifen. It can only be given to postmenopausal women though.

Member_of_the_Club

Hopefor I got the same advice from my onc and my sense is that most feel this way, and the trend is away from recommending the test.  I trust my onc.  he said to me point blank "my job is to do everything I can to increase your chances of survival," and he doesn't recommend the test.  I'm four years out and doing great.

every8thwoman

Hi everyone,

I didn't see this thread when I posted that I had been taken off Tamoxifen and put on Fareston.  I am a poor metabolizer of tamoxifen too.  Instead of upping the Tamox dose, my onc put me on Fareston (60mg) which bypasses the inactive enzyme that breaks down tamoxifen.  Apparently 15% of the population lacks the enzyme to break down Tamoxifen so that translates to a lot of sisters taking Tamoxifen and thinking its working.  I was on Tam for 15 months before I took the test.  I would love to see how much endoxin I have in my system, because if thats the actual estrogen blocking metabolite, that would be the true indicator for a patient.  Anyway, thanks for the input.  I feel better now that I've talked to people who know more about this medicine.  I think my side effects are less on Fareston than on Tamox. 

KathyNSW

Hi Everyone,

I was hoping to get some advice. I am from Australia and I did the 2D6 test and the results were I was a poor metabolizer of Tamoxifen. They don't really recognise this test( or others for that matter)  here for routine checks. What would be my next option?

Should I have my ovaries removed or have injections. Am interested in this other test to test endoxifen.I am premenapause and how accurate is this test and should we solely rely on these results.

What is fareston?

Thankyou for your help.

Kathy

RyKriTe

Have you seen the study that says that women who experience more severe side effects from hormonal treatment (AIs and tamoxifen) are more likely to have disease-free lives.  I wonder if there is a correlation between poor metabolizers and low side effects?  My onc told me that within a month of starting tamoxifen if I did not have worsened hot flashes she would assume I was a poor metabolizer and she'd run the test, but she had found a very close correlation.  My insurance will fight me on the test, so we're doing it this way (which feels weird to me, but still okay).

KathyNSW

Hi RyKriTe

I have heard something about it,,is there an article or website that I can go on to.

I have had alot of hot flashes, but the chemo could of done that and sometimes I

feel a bit light headed but really not much to worry about. I am not sure what to do

Should I have my ovaries removed and will that bring a new set of problems.

Thankyou for your quick response

Kathy

TenderIsOurMight

Hi Kathy,

I've studied up some on this CYP2D6-Tamoxifen relationship, which is a work-in-progress. For your Australian doctors, here is the Mayo Clinic physician's summary on this research. Dr. Goetz and colleagues have published widely on it. There is no test for endoxifen as yet.

http://www.mayoclinic.org/news2008-rst/5125.html 

Since your test results suggest you poorly metabolize Tamoxifen into endoxifen, felt to be the active agent, most who believe in the test would suggest a switch to a different hormonal. As you mention, fareston seems to be an alternative, and recently we had one member post on this if you care to use the forum search. Fareston is metabolized through a different liver enzyme genetic grouping than Tamoxifen.

Alternatively, some do undergo surgery to remove their ovaries and then start an aromatase inhibitor (Aromasin, Arimidex or Lexapro). One risk of getting Lupron shots and taking Tamoxifen is the Lupron is unable to adequately suppress ovarian function, so your ovaries remain somewhat active. This can lead to bleeding and cysts.

Now that you've done the test, I'm sure you'll try to find an open minded oncologist to help you. Perhaps there are other Australian members here who have found an oncologist mindful of this research and they will contact you or post on this thread.

Best to you,

Tender 

Member_of_the_Club

I don't know that hot flashes are the only side effect of tamoxifen you should be focusing on.  I wonder if anyone else (Tender?) has some thoughts on this.  My hot flashes didn't get worse on tamox because I was coming out of chemopause.  I still have some hot flashes but nothing like what I had during chemo.  I would think many women on tamoxifen would experience the same dynamic since most of us who are premenopausal get our periods back.

I had other side effects on tamoxifen -- initially, nausea, very prolonged and heavy periods, migraines, increase in anxiety, increased bruising.  All of these went away eventually, but I do think I was experiecing SEs of tamox without increased hot flashes. 

TenderIsOurMight

Hi All,

I too wonder about these reports about hot flashes. Not so much of what they say but their corollary suggestion that without them you don't metabolize hormonals as well. At least in my case on Arimidex and now Femara, I've never had extensive hot flashes. Just one good long flash about two hours or so after taking the pill, perhaps a second one later that night. I have not had a blood test of late to correlate findings with the new Femara rx.

I often wonder if my slight belly fat has enough fat to counter act and that's why I don't flash. But then I realize that my estrogen sensitive tissue is so deprived that my worry is illogical. If clinicians use the hot flash (wide definition and subjectivity amongst us) as a reflection of hormonal workings, then a prospective study amongst takers of expertly done serum estradiols and recordings of hot flashes may give a better idea on this issue.

Good points,

Tender 

jezza

Hi KathyNSW!

I have sent you a private message.

Go to My Home at the top of the page to retrieve it.

jezza

orange1

Hi Kathy

Since you are a poor metabolizer of tamox and ER+, you need to do something to block the estrogen.  I am guessing shots + AI inhibitor if you are still premenopausal.  You need to find an onc who's up on the literature, or at least one who is willing to be educated. 

orange1

Kathy -

I should have added to my last post - Perhaps try to see an onc associated with a teaching hospital.  They seem to be up on the latest research.

Good luck

KathyNSW

Thanks orange1

I will be seeing my onc next Monday to discuss this. I am pre menapausel but haven't had a period for 6 months so sort of stuck in the middle. Not classed as being in menapause . I thought the als were for post menapause.Is there any other tablets other than tamoxifen for pre menapause and why don't they recommend the test for pre menapause.

Take care everyone , I will keep you posted

Kathy

XXMadisonXX

I had the CYP2D6 test done - one of the first at my cx clinic to ask for it. And none of the oncs there knew what to make of of the resuults.  I came out as intermediate -- I actually pulled up more info from internet research than the oncs at the clinic.

I discovered - (not any of the oncs) - that the dose should be lowered. But none of them knew what dose to lower it to.  My onc did do some research and said there just weren't any studies out there on a proper lower dose -- probably because it's an older drug.

I did find a long research paper on a lower dose -- but by the time I found it I had decided not to take Tamox.

I will try to find it on my hard drive and upload it

KathyNSW

Thankyou for the article Tenderisourmight. I will show it to my onc and let

you know what she says with all this info.

Take care

Kathy

KathyNSW

Hi everyone,

Saw my onc today and told her about the test and my results. She had never heard of it and told

me there was alot of crazy stuff on the internet. Told me since I was pre menapause my only

option was Tamoxifen. Haven't had a period for 8 months so i guess I am not producing estrogen

in my ovaries, which is good in that respect.

Not sure what to think or do. How accurate is the cheek swab test?

Thanks everyone

TenderIsOurMight

Hi Kathy,

Sorry you're oncologist refers to internet crazyness when it comes to expert discussion (Goetz, Flockhart, etc) on Tamoxifen metabolism. But at least you yourself know there is reasoned debate over how individuals metabolize Tamoxifen (a prodrug) into active endoxofen and what to do if you're in the poor metabolzer status, which includes about 7% of takers. 

In 2007, I researched the cheek swab for the CYP2D6 test (also known as a "buccal" swab). Personal DNA can also be obtained from the mucosa of our cheek. Here is a repost of this post:

Aug 15, 2007 07:13 pm, edited Mar 19, 2008 12:42 PM by TenderIsOurMight
TenderIsOurMight wrote:
Kate and All,

I checked around a little on this cheek (buccal) vs blood DNA sampling method. It appears most reference the below abstract (with link) when addressing accuracy:


Link:http://hmg.oxfordjournals.org/cgi/content/abstract/2/2/159

"Multiplex PCR amplification from the CFTR gene using DNA prepared from buccal brushes/swabs

Brenda Richards*,, Joel Skoletsky, Anthony P. Shuber, Rosemary Balfour, Robert C. Stern1, Henry L. Dorkin2, Richard B. Parad3, David Witt4 and Katherine W. Klinger
Department of Genetic Disease Research, Integrated Genetics Framingham, MA 1Department of Pediatrics, Rainbow Babies and Childrens Hospital Cleveland, OH 2Department of Pediatrics, Tufts, New England Medical Center Boston, MA 3Divisions of Pulmonary and Newborn Medicine, Department of Pediatrics, Harvard Medical School and Children's Hospital Boston, MA 4Kaiser Permanente, San Jose, CA USA

* To whom correspondence should be addressed at: Integrated Genetics, One Mountain Road, Framingham, MA 01701, USA

Received October 5, 1992; Accepted December 1, 1992

Traditionally, DNA used for PCR-based diagnostic analysis has originated from white cells fractionated from whole blood. Although this method yields substantial quantities of DNA, there are some drawbacks to the procedure, including the inconvenience of drawing blood, risk of exposure to blood-borne pathogens, liquid sample handling, and the somewhat involved extraction procedure. Alternatively, DNA for genetic diagnosis has been derived from finger stick blood samples, hair roots, cheek scrapings, and urine samples. Oral saline rinses have also been used extensively as a means of collecting buccal epithelial cells as a DNA source. However, this method still requires liquid sample handling. Herein, we present our results involving the rapid extraction of DNA from buccal cells collected on cytology brushes and swabs for use in PCR reactions, specifically the multiplex amplification of 5 exons within the CFTR gene. The quality of DNA isolated from buccal cells, collected in this manner, has been sufficient to reproducibly support multiplex amplification. Cheek cell samples and the DNA prepared from them as described here are highly stable. The success rate of PCR amplification on DNA prepared from buccal cells is 99%. In a blind study comparing the analysis of 12 mutations responsible for cystic fibrosis in multiplex products amplified with DNA from both blood and buccal cell samples from 464 individuals, there was 100% correlation of results for blood and cheek cell DNA, validating the use of DNA extracted from cheek cells collected on cytology brushes for use in genetic testing."

And from the link:http://cebp.aacrjournals.org/cgi/reprint/7/8/719.pdf is the following quote:

"The validity of using DNA isolated from buccal cells has been demonstrated in previous studies." which references the above Richards study, apparently considered a classic reference on this topic.

One point which I did see raised was that the swab must be processed timely or else placed in a preservative.

So.. it appears that this cheek swabs are accurate. It makes me wonder whether all breast cancer patient's should know their CYP status in general, given how many drugs some of us are on. Arimidex is metabolized through a different CYP liver enzyme, but one which lots of other drugs are metabolized also.

Great question. Hope this helps.
Tender

KathyNSW

Thankyou so much  Tender.

That has helped heaps. I think I will have to get a second opinion

Has anyone else got a second opinion.

Thanks again Tender, I will print that off.

Lolita

I threatened to get a second opinion, and then my oncologist gave me the test.  Good luck to you.

Jisman

KathyNSW - don't jump to the conclusion that since you haven't had a period that you are no longer generating estrogen.  The doc can run a test on estrogen function.  My onc runs it every 3 months for me - still generating estrogen .  Haven't had a period in 6 months.

Tender -  Curious as to your background and your research aptitude.  You seem to be very well connected.

My onc doesn't regularly run the CYP2D6 test.  He's willing to run it for me if I really want it however he says since there isn't conclusive info on what to do for the various results that unless I would be willing to go for the ooph and change to AI, no sense to run the test.

Joan

every8thwoman

Hello Jisman,

Before you go under the knife, please inquire about Fareston.  I am premenapausal, and a poor metabolizer of Tamoxifen.   I did NOT undergo an ooph.  I was put on Fareston which uses, as Tender has said, a different metabolic pathway than Tamox.  You should check this out as another option.  If your onc doesn't think this test makes sense-give serious consideration to finding another onc who is more knowledgable!!!

Alaina

I had my bloodtest for the Tamoxifen metabolization yesterday.  Also talked to Onc about things to consider to continue to suppress estrogen after all my treatments are done.  I asked about the oopherectomy and he said it wouldn't be a bad idea.  So more things to consider.

Anxiously awaiting my test results!

Alaina

Northstar

Although my medical onc. does not typically do the CYP2D6 test, she was at the conference in Dallas in Dec. where it was recommended and knows that Mayo does it.    The oncs in Boston all pretty much have the same opinion, I have found.   I decided to get it done on my own and found that I am a normal metabolizer.   I showed her the results and she was very interested and said she might start doing it for some of her post-menopausal women.    I really didn't want to NOT know this piece of info.   I've been having hot flashes on tamoxifen, but nothing else.  

phoenixrising

This is the updated monograph for Tamoxifen

 http://www.astrazeneca.ca/documents/ProductPortfolio/NOLVADEX_PM_en.pdf

which includes this information:

NOLVADEX is a pro-drug requiring metabolic activation by CYP2D6. Inhibition of

CYP2D6 can lead to reduced plasma concentrations of an active metabolite (endoxifen) of

NOLVADEX. Chronic use of CYP2D6 inhibitors, including certain SSRIs, together with

NOLVADEX can lead to persistent reduction in levels of endoxifen (see also

PRECAUTIONS, Drug Interactions). The clinical significance of this in terms of efficacy of

tamoxifen is unclear. Concurrent use of SSRIs with tamoxifen therapy should be avoided.

This should eliminate any doubts as to the connection between cyp2D6 and endoxifen.  Therefore I can't imagine not being tested esp due to the risks involved.  The relationship between se and metabolism of the drug I think should be viewed with caution as many many women who are poor and intermediate metabolizers have horrific se and many women who metabolize normally have few se.  I think there is much more to be learned about this topic.  I had more hot flashes before dx than I do on Aromasin now.  So someone please tell me how that works??? 

jan

HelenaJ

Hi everyone, have been on another thread "bottle of Tamoxifen" and was just wondering if anyone here knows how long you have to be on Tamoxifen before you can get the CYP2D6 test done?

Helena

Lolita

Helena J,

You don't even have to be on tamoxifen to take the test. CYP2D6 measures your ability to metabolize tamoxifen and other drugs, not the amount in your system...Lolita