CYP2D6 ability to metabolize tamoxifen and recurrence

*1 appears to be the active allele, and *4 is inactive. I was hoping for at least partially active. I can't get in to see my oncologist until July 5th, but I am going to double my dose of tamoxifen in the meantime, which is one of the recommended alternatives. That may compensate for the decreased metabolism.

I am steaming a little over the fact that everyone on tamoxifen doesn't automatically get this test!

My full results:

The disability reference example of above. This is off topic, but it's another example of being proactive. I had a brain tumor that was dx'd at the same time as BC. I was offered a craniotomy or proton radiation. The crani was the top of head approach. Being an old OR nurse. I knew that approach for where the tumor was could lead to many complications and or disability as the brain was lifted. I firmly believe in Dr. Google, but I do have the advantage of understanding the lingo. What I found was a "base of the brain" surgical approach. Not offered in my county. Not offered by any of the big wig docs. I found my own hospital, NCCN Moffitt cancer center. Successful, excision without disability.

Hi live_deliciously, please let us know how it goes and details about how and where you're getting it done. Did you not need a doctor's referral? Is your insurance covering it? What has your experience been with tamoxifen and side effects so far?

Sorry for the 3rd degree but this info will be very useful to others who come after us.

Good luck!

Here's the study referenced in the YouScript report regarding dose escalation in PMs and IMs that led me to double my tamoxifen dose while I'm waiting to get in to see my MO about the results:

Tamoxifen Dose Escalation in Patients With Diminished CYP2D6 Activity Normalizes Endoxifen Concentrations Without Increasing Toxicity

This seems like a valid option for me. All I have noticed in the 4 days at 40mg is a few extra hot flashes. This is interesting because some studies show increased hot flashes in IMs and PMs over extensive and ultra rapid metabolizers, but that has not been my experience. It was the mildness of my hot flashes and complete lack of night sweats that led me to suspect I was an IM to begin with. And the normal and ultra rapid metabolizers we have heard from here had worse side effects.

I wish I knew my new MO better, and how creative he is willing to be in terms of individualizing my treatment. I would be willing to try the 40mg for a month if he is willing to test my endoxifen levels at the end of the month, but of course it's not a standard test and he was very stuck on the standards at our first appointment.

I'm not against switching to an AI per se. I had planned to do that anyway at the 2 year point, which was when my old MO estimated we would know for sure if I was permanently in menopause or not. It is the ovarian suppression I'm having a hard time with, just because I am so close to menopause. I'm probably actually already in it, we just don't have confirmation yet. In the last nine months I have had one period and one spotting incident, and my FSH was menopausal in February. My mom had her last period when she was 52 and I am 52, and her menopause followed the same pattern that mine has. An abrupt end, with one more random period before going for good. MO wants to do OS for 3 years, which I do believe is going to be overkill, and it will add on to the adverse effects of the AI. Added bone loss for instance.

Any thoughts?

Solfeo, The evidence is certainly mounting for testing. It was nascent in 2009 when Jelson started this thread. Greg Pawleski hasn't been here for years. He is the consummate researcher, but tended toward believing the stuff. If you go back to page one and two you can see the discussion. It would be tedious, but a look back to see the historical difference would be interesting. But we do reach a time that we say enough is enough "just give me the down and dirty".

You may find it interesting to click on his web site

You are on this side of BC and soon to be on this side of menopause, considered getting the puppies out. Supression, has been the modus operandi since Tamox came to market. They are worthless now. One less body part that can kill or maim. I'm ruthless, aren't I. We all know what one stray cell can lead too. That being said you know that recent studies will shed some light. Forget ASCO. They are way to conservative. By the time they make a recommendation the info is years old. Damn, am I in some sort of mood this morning? I may delete that sentence after you read it.

It sounds like you are mentoring Live nicely, I won't weigh in.

Thanks for the update live_deliciously. It would have been nice to find out anyone could get it done on their own. Along with the lower cost of Kailos that would have made the test more accessible to more people. Genelex told me I wouldn't get my hard copy of the results until a week after the doctor, though, because they want you to talk to your doctor about the results first. I understand that these things can be misinterpreted, but from what I have seen, by the time one of us wants this test we know more about it than our doctors do. I had to go around my MO to get it. I'm dreading talking to him about the results on Tuesday because I already know he doesn't believe in the worth of the test, so how can I trust his advice on what to do about it? I'm still going back and forth between continuing on the raised dose of tamoxifen and switching to AI+OS.

I had to give myself the test because my ND didn't want to do it on Friday and have it sit around hot post office over the weekend. It was easy, just rub cotton swabs around in your mouth (unless Kailos requires you to go to a lab for a blood draw, which was an option with Genelex if you wanted).

Definitely keep us posted!

I can't take any credit - I got the info from McClure77!

I apologize if this has been asked in the past, but why can't we just measure the amount of active endoxifen in the blood? Why would a genetic test for CYP2D6 be better?

"Boronic prodrug of endoxifen as an effective hormone therapy for breast cancer" (2015)

http://link.springer.com/article/10.1007/s10549-015-3461-9

"As a prodrug, tamoxifen is activated by the P450 enzyme CYP2D6 that is responsible for converting it to the active metabolites, 4-hydroxytamoxifen and endoxifen . . . Endoxifen is currently undergoing clinical trials as a potentially improved and more potent SERM (Selective Estrogen Receptor Modulator) for endocrine therapy that is independent of CYP2D6 status in patients. However, direct administration of endoxifen may present the problem of low bioavailability due to its rapid first-pass metabolism via O-glucuronidation."

In addition to the "ADME" challenges, the observation of (at least) two known active metabolites of tamoxifen might also impact how efficacious a single active metabolite will be as a therapeutic.

BarredOwl

Yeah, I'm curious why they don't routinely test for endoxifen. Is it super expensive or something? You'd think if it's just a blood test it wouldn't be a big deal.

i wanted to log my tamoxifen metabolizing test. They sent a fax to my med onc to approve the test because they want a Dr to get the results as well as yourself. They then sent the test kit to me within a couple days. Here is the letter that describes the next steps. Well i Can't get a picture of the letter to attach. Anyone know how? I chose the picture icon and have tried using the camera feature and attach the document feature? Just shows a moving blue bar across the top. I thought it was uploading but it took too long

Solfeo, I'm so glad you have an MO who is flexible, caring, and willing to personalize your treatment! Sounds like you have a solid game plan now.

I guess I am confused as to why doctors don't use CYP2D6 test results. Seems like you are a textbook example of how treatment can be altered based on your specific alleles. I also don't know why they don't routinely check endoxifen levels to see if tamoxifen is working initially, and is maintaining it's effectiveness. The way it is now, it's like throwing darts at a board and not caring where they land.

Live_, hope you figured out how to get the picture of the letter to attach! Wish I could help, but I hate computers and they hate me.

Live ~ To post a copy of your letter....

Using a computer; scan the letter and save it as a jpeg on your desktop. Be sure to name it so you can find it easily. Next, post it as a picture using the "Insert Image" icon you see at the top off this reply box here on the boards. Click the "choose file" button and select "desktop" and select the image you want to post.

Using a tablet or phone; Take a picture of the letter and save it to your gallery as a photo. When posting use the "Insert Image" here icon. After clicking the "choose file" button, you will be given a choice as to where you want the image to be pulled from. Depending on your device, you will have your "gallery" appear as one of your choices. If not, you may have to select "documents" and then "gallery" to choose your image.

If you do not have a scanner, you can use your phone to take a picture, email to yourself and then save to your desktop or gallery to post it here.

If you have the letter saved on your computer as a PDF, open the file, select "print" and then change the print option to allow you to save it as a jpeg on your desktop. Follow the steps above and post the letter as a picture.

Hope this helped!

Edited to add;

If your picture looks like it is loading and then doesn't try signing into your account again and then re-trying. If the memory on your tablet or phone is getting full it can block you from properly posting a picture. You can add room to the memory by deleting old photos, messages and by clearing your browser history.

Shepkitty, I was definitely bracing myself for disapproval of my decision to take matters into my own hands in the interim between test and appointment. I handed him the studies first and told him what they found about the elevated dose. Then I asked him what he thought so I could address his concerns, if he had any, before he knew what I had done. His only concern was the possibility of added side effects but he didn't say anything that sounded like he was against the idea. That was when I looked at him sheepishly, and said, " Don't get mad at me, but since I couldn't get in to see you right away and there was so much evidence supporting this as a way to raise endoxifen levels with no toxicity, I went ahead and doubled my dose right away. I didn't want to waste any more time" He just smiled. I already told him that I am a high info patient, that I do my homework and read every study, and that I am very well educated about the specifics of my disease. At that point I could already tell him there have not been any adverse effects in almost 2 weeks at 40mg, so what could he say. Like everything else I do, I do not necessarily recommend others follow in my footsteps in this way.

20mg is the usual dose, but 40mg is still in the acceptable dose range. There was someone in the tamoxifen thread who was prescribed 40mg/day from the beginning. That being different from what most of us were getting, she asked her pharmacist and he said up to 80mg was acceptable. The reason they don't prescribe the higher doses as a rule is because there was at least one study that showed there was no added benefit over 20mg, and in order to minimize side effects. Of course they weren't looking at CYP2D6 IMs and PMs. So 40mg isn't that far out of the box and I won't be taking it that long anyway.