There are a lot of long posts on the CYP2D6 pathway for Tamoxifen.  Your medical enzyme pathways are important to know if Tamoxifen and other drugs will work for you at the normal dose.  The Mayo Clinic has published a report agreeing with this assessment (https://cpicpgx.org/content/guideline/publication/tamoxifen/2017/tamoxifen_reprint.pdf)  Also https://newsnetwork.mayoclinic.org/discussion/new-international-practice-guidelines-for-tamoxifen-treatment-based-on-cyp2d6-genotype/ 

I used www.kailosgenetics.com and order the rxcomplete test.  Not only did I find out I'm a Ultra-rapid metabolizer on the CYP2D6 pathway, I also found out I"m a Met/Met (double mutation allele) on the COMT enzyme.  COMT is the trashman for our bodies and cleans out trash estrogen.  I have very little COMT due to the mutation.  It makes sense I got ER+ breast cancer and also estrogen based Melanoma.   I had my whole family take the test...  my husband is a Met/ met too... (which means so are our kids)  and he was just diagnosed with Melanoma as well.   

Ladies, please consider getting tested.  When I got tested it was 'alternative' because my Oncologist had never heard of it.  Science and studies are finally starting to catch up.  

My MO had never heard of it, I found Kailos thanks to the ladies on another thread a few years ago.  They were one of the 4 FDA approved labs in 2016, and I absolutely love that they will work directly with the patient.  I just plugged in my docs names, and then 'informed' my doctors of my family I had ordered this test and they 'needed' to authorize.  I'm paying for it myself, so you can just be assertive.  My kids pediatrician had no idea what it was either, but as long as insurance isn't involved, they don't care. 

It is my view that in a decade or so this will routine screening on newborns.  It's information we absolutely should know about our own pathways. 

I know the other 3d4 pathway is tested, the trick is to go to drugs.com and see what the primary pathway your medicine is on. As for me , when I found out I was low on the COM T Enzyme I was able to up my green tea catechins, to help block er levels. My husband found out he can't take nsaids... these tests are truly important for far more than breast cancer

I'm thinking of getting this test done. I was diagnosed a little over 2 years ago with a cancer that was 100% ER positive. Theoretically, tamoxifen should work really well. But it didn't. I had a local recurrence where cancer cells seeded during the biopsy grew big enough to form a palpable lump within 18 months.

Now I'm on Zoladex, and as soon as my estrogen levels are low enough, I'll be switched to an AI. But I can't help but wonder why they didn't test my CYP2D6 pathway metabolism. I even asked my MO about it soon after starting tamoxifen. She dismissed it, but now I wonder: am I a poor metabolizer? Is that why it didn't work for me?

I didn't realize the test also looks at pathways used by AIs. That will be important information for me to have before they switch me from tamoxifen to exemestane. Thanks for the info, Lisey!

I could only find this test actually for your AI: https://www.biomol.com/products/toolkits/other/aromatase-cyp19a-inhibitor-screening-kit-fluorometric-g-bn01142.100

I don't quite trust ".com" sites to have the consumers' best interests in mind on medical issues, unless recommended by my doctor.

Hey Alice,

I agree that it's worthwhile to be skeptical of a .com site, but anyone can buy a .org site too.

the AIs use the P450 family pathways... the 3A4 is one of them, responsible for about 25% of all medication pathways.  I remember that the Ais don't use the same pathways as Tamoxifen 2D6, and think some you at least a percentage of the P450 3A4..   But I'm not certain since I'm avoiding Ais since Tamox works well for me. 

As for the site, due diligence ladies... do your research yourselves and realize most doctors will never suggest these tests as they are cutting edge and not a standard of care (yet) .. 

I had blood draw just yesterday for this test. After I spoke with MO again she said will do it, no problem but she said she will send it to Mayo. I will sure come back and tell what i find out. I started Tamoxifen on March 14 but i still fell she rather wanted me on AI

HI Rah,

So from what I understand there are two types of drug metabolism.  Tamoxifen is a 'pro-drug' , a type which requires metabolism first for the drug (endoxifen) to be formed.  Therefore, it's the reverse of the other type of metabolism where you would want slow metabolism to get all the drug in your system.   Which means an ultrarapid like myself would probably do well on a lower dose, but a intermediate would actually need MORE tamoxifen to make the same Endoxifen needed.

Here's what one of our chief scientist posters said in another thread:

BarredOwl: Some confusion back in the thread (which Solfeo noted) and in general stems from mis-understanding of the distinction between a drug that is the "active per se" versus a drug that is a "pro-drug" which is metabolized to produce the active(s). This affects the appropriate dose adjustments in opposite ways.

One example would be a drug that is the "active per se", and for which metabolism via CYP2D6 reduces the amount of the active, producing inactive or less active metabolites. In a CYP2D6 ultra-metabolizer, the active drug would be rapidly converted to inactive or less active metabolites, so a dose increase would be considered. Conversely, in a poor metabolizer, the active sticks around, and a dose reduction might be considered (depending on its pharmacokinetics).

With a drug that is a "pro-drug", metabolism of the pro-drug via CYP2D6 produces the active(s) (e.g., tamoxifen is metabolized by CYP2D6 to produce the more active endoxifen metabolite). In a CYP2D6 ultra-metabolizer, the pro-drug (e.g. tamoxifen) would be rapidly converted to the active (e.g., endoxifen), so a dose decrease might be considered. Conversely, in a poor metabolizer (e.g., tamoxifen is not efficiently converted to the active endoxifen), a dose increase might be considered.

The 4 metabolism types are:
UM: Ultrarapid metabolizer
EM: Extensive metabolizer  (NORMAL)
IM:  Intermediate metabolizer
PM:  Poor metabolizer

Here is a question: if one is on AI, is it sufficient to measure estradiol level to see if it's working? If I understand mechanisms of Tamoxifen and AI correctly, the former works to block estrogen receptors of the cells, and while estrogen level in the blood may remain high, it should not "enter" cancer cells and therefore prevent tumor growth. For AIs, the end goal is to reduce circulating estrogens to a very low level.

There is some controversy on what level of estradiol is considered "good" for those on AIs, but isn't a relatively low level a good enough indicator that AI is metabolized normally?

Also, just a word of caution - I'm an IT/security professional, and I'm super wary about giving anyone access to know and store my genetic data. Most companies have poor understanding of data security and protection, don't follow best practices, and as a result, are victims of hacks and security breaches. It's enough that everyone in the US who ever had any credit has their SSN floating somewhere on dark web (hello Equifax), I need to know for sure what I will do with the info I get out of a genetic test before I risk the same with my DNA info.