Elimar, the Genelex kit is the first I've heard of a cheek swab.  I had mine done through a blood test ordered by my onc -- the results page came back from ARUP Laboratories.

Okay, I have an olive branch -- and a challenge -- for Kashcraft.

As I've said, I think the information she has provided here and elsewhere has been very useful.  I'm even going to refer one of my "chemo buddies" to this thread, because she asked me about CYP2D6 testing last week.  I have no objection at all to the content, or quality, of the advice Kashcraft has offered.  My only concern -- and it's just a niggling little ethical one, not a huge deal -- is whether we're on a slippery slope.  Can we pick and choose whose "helpful" information we want to see on these boards?  Are some "promotional" posts more acceptable than others?  Who decides?  (I know; the "Community" decides.  But I happen to think the "Report this Post" process sux, and I'm not even thinking about using it anymore.)

So, here's the challenge for Kashcraft...  Surely, someone who knows so much about the technical aspects, indications, and reimbursement issues, of a laboratory service her company offers, also knows of other, similar tests offered by her company's competitors.

I would be much more at ease with the "commercial" content of this thread if Kashcraft would stop in and provide us with a list of the other tests for CYP2D6 that might be available through other companies or labs besides her own. It would be even better if she would explain the similarities and differences among all those tests.  Which ones require a blood sample, versus a cheek swab?  Which ones can be, or must be, done on tumor tissue?  Are there any other issues (pertaining to the various companies' tests) that we ought to know?  But, let's be objective about it -- let's not give the impression that we're promoting one of the tests over the others.

Even if she really is a "molecular biologist", Kashcraft ought to know who else is doing testing similar to the test her company runs.  Heck, I was a lab rat (translation:  a lab tech/research person) for quite awhile in a previous life.  We all knew the places and people who were doing work similar to ours ... especially when that work was cutting edge or had patent potential.  You have to know who your competition is, and what they're doing.

In some cases, there is only one lab or company performing a particular test.  The "Oncotype DX" test for recurrence risk might be an example -- it's my understanding that the the only place here in the U.S. that's routinely doing genetic testing of tumor tissue to predict recurrence risk is Genomic Health.  (I know there are other tests -- like "MammaPrint" -- from other companies; but I don't know if they're widely available here.)  BRCA testing I think might be different -- much of the BRCA testing is done by Myriad Genetics; but I think there are other labs doing it, too.  We just don't hear as much about them.

So, I assume there are other places besides Genelex that will do genetic testing for the CYP2D6 alleles.  Let's see if we can produce a list.

otter 

There is an eMedicine article on the testing, from October, and they list LabCorp and a second lab:

http://emedicine.medscape.com/article/1762071-overview

Testing for the Genetic Mutation

The Roche Cytochrome AmpliChip P450 2D6/2C19 Genotyping and Phenotyping Assay can be used to identify 26 different alleles of CYP2D6, including *4.

The following companies offer testing for CYP2D6 variants:

DxS (http://www.dxsdiagnostics.com/)
LabCorp (http://www.labcorp.com/)

I also found a clinical trial done by Medco and they used LabCorp.

I also found an older Blue Cross technical review, and they concluded the test was of no utility and wouldn't cover it: with all the new information, I hope their policy has changed

http://www.bcbs.com/blueresources/tec/vols/23/cyp2d6-pharmacogenomics-of.html 

Kira 

Kashcraft (Kristine), THANK YOU!!!

otter 

Both my oncologists (local and at the big cancer center) refused to order the test! This makes me so mad! I am having extreme dry mouth on tamoxifen and I'm starting to think that it might be because I'm a poor metabolizer and the buildup of tamoxifen in my blood is toxic. I have read this about other drugs and CYP2D6. I am going to a different doctor in 2 weeks who does believe in the test. I hope my insurance will pay for it. My sister was tested and she is a poor metabolizer. She is taking toremifene instead of tamoxifen. She didn't have any symptoms like dry mouth on tamoxifen though, so I don't know what to think.

I asked for an email confirming that the price truly is $362 before they send out the kit, but I haven't received one yet. I don't like to get a bill after the fact, because medical establishments try to just charge you whatever they want. So now I'm getting a bit nervous...

Okay I tried googling a bit and can't find anything other than there is no evidence that one thing causes another, though it seems like it would (no evidence that poor metabolizers have higher recurrence rates I guess, although it seems that this would be the case.)

My MO told me it's not very accurate. I don't know if that's true; just passing it along.

Hi Susan:

I agree that it is the meaning of the test result that is not understood. It may be more accurate to say that, as of this date, due to conflicting results, the use of this candidate biomarker (CYP2D6 genotype) is not sufficiently validated in the clinic for the purpose of deciding whether to take tamoxifen.

The evidence for thinking that CYP2D6 function affects endoxifen levels seems quite sound. This is the rationale for clinical testing of CYP2D6 mutation as a candidate biomarker to see whether or not it can provide reliable predictive information about clinical benefit from tamoxifen as hypothesized.

The apparent inconsistency you note between the views on use of genotype vs use of antidepressants might possibly be question of the level and consistency of clinical evidence available on each question and differing clinical postures.

As of this date, the studies that looked for an association between CYP2D6 mutations and decreased clinical benefit of tamoxifen are conflicting. The reasons for this conflict are in debate.

At least one retrospective clinical study raised concerns that certain antidepressants may decrease the effectiveness of tamoxifen and may result in worse outcomes. (Advice may differ depending on the particular drug.) This is thought to be mediated by the known CYP2D6 inhibition properties of the drugs (maybe in vitro), but perhaps that is not the whole story of what is going on inside the patient.

Also, if you have a potential biomarker (CYP2D6 genotype) that has not been shown to reliably correlate with lack of benefit in the clinic (because of conflicts in the clinical validation studies), clinicians may hesitate to make treatment recommendations based on genotype and risk possible under-treatment.

On the other hand, if you have a drug like tamoxifen with established clinical benefit, and there is some evidence or suspicion that said benefit may be reduced by concomitant use of certain medications, it may make sense to avoid the drug-drug interaction when feasible, (even if precautionary for some).

By the way, this is what I have in my file about CYP2D6 genotyping:

Here is a 2015 article that discusses the conflicting clinical studies on CYP2D6 mutations:

http://jnci.oxfordjournals.org/content/107/2/dju43...

This recent article from Medical News Today discusses two abstracts at SABCS 2015 regarding CYP2D6 genotyping and mutations.

Article: http://www.medicalnewstoday.com/articles/303942.ph...

Abstract #1: http://www.abstracts2view.com/sabcs15/view.php?nu=...

Abstract #2: http://www.abstracts2view.com/sabcs15/view.php?nu=..."

The conclusion of Abstract #2 is particularly interesting (emphasis and bracketed text added by me):

"Conclusions: Polymorphisms in CYP2C9 and CYP2D6, but not [the] other enzymes or transporters [tested], contribute to variation in endoxifen exposure. If endoxifen exposure is validated to predict tamoxifen efficacy, personalized tamoxifen dosing algorithms should include CYP2C9, in addition to CYP2D6 and clinical factors, to improve efficacy and minimize side effects."

NCCN guidelines (Version 1.2016) provide: "At this time, based on current data the panel recommends against CYP2D6 gene testing for women being considered for tamoxifen therapy."

While testing of new patients is not recommended under current NCCN guidelines (Version 1.2016), those who have already received such testing are faced with uncertainty and little guidance.

BarredOwl

Peggy,

I can't answer your primary question, but on related notes

1. The severity of side effects is not an accurate indicator of how well Tamoxifen is working.

2. Estrogen deficiency causes bone loss. Your initiated estrogen deficiency when you chose to have your ovaries removed.

Peggy, you're right. When I was thinking about Tamoxifen working, I was only thinking about it from a breast cancer standpoint, not the bone strengthening capabilities that Tamoxifen should exhibit, that women need.

https://www.kailosgenetics.com/tamoxifen

I did this test within the last year. It is $99 self pay. My onc was fine in approving the test even though I initiated it. The result was that I was a normal metabolizer of Tamoxifen.

hmm - Good question. I also did genetic testing via Color Genomics via a saliva sample and I was looking for reviews on them. Here is something I found http://geneticmedicineclinic.com/colorgenomics/

That doesn't answer your question, but does touch on the issues surrounding lab reliability.

Thanks Farmer Lucy and Pi-Xi. That's helpful. My MO ordered the blood serum test and it goes to the Mayo Clinic. I guess if accuracy is paramount, you can't argue about going that route.

In my research I stumbled across this doc (with a 130+ page PDF!) on the cost-effectiveness of doing this test. Buried in there, somewhere, is a statement that the Mayo Clinic charged about $500 (this doc was pubbed in 2011).

https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH00161...

I called Mayo last week and the guy I reached wouldn't answer my questions on pricing and referred me back to my doctor's office. I emailed them today. Maybe that will go to someone who wants to help. (Meanwhile, my insurance company says they don't automatically pay, so I'm asking my MO's nurse to work on getting the pre-approval).