CYP2D6 ability to metabolize tamoxifen and recurrence

I don't know the answer, Jelson, but to add some thoughts to the mix that bring up more questions: I don't fully understand this myself but I read something that led me to believe some drugs recirculate through the bile after they have been in the bloodstream, so they may make their way to the liver eventually. Maybe not all of them and I'm sorry I don't remember more details, but something for us to check into when we have time.

unfortunately, Kailos does not provide services to people in the state of New York. I tried to register as a New Jersey resident, but they want my shipping address to match this. Anybody knows a way around

Ugh... That's an option... The other one is to try and convince my MO to order the test from Genelex, but she already told me that she does not test for CYP2D6 due to inconclusive results. She's in favor of removing ovaries and switching me to AIs anyway, so probably not that interested in CYP2D6. I've been on tamoxifen 3 weeks, would like to know if it is effective at all for me.

Lisey, I hope you don't mind me answering but I have actually done a lot of research on this. This is what is concerning. CBD is a potent CYP2D6 inhibitor, which is exactly what we need to avoid:

Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6

Read the whole study. They question whether the effect might not be as strong in the human body but they are not sure because of prior unexpected results with Prozac. I would personally not take the chance while on tamoxifen.

"CBD is not anticipated to exhibit in vivo inhibition of CYP2D6. However, we cannot exclude the possibility that the in vivo inhibition potency of CBD is underestimated because there is an example that the predicted ratios of AUC _inhibited with fluoxetine to the AUC _control of CYP2D6 substrates are 1.1 to 1.5, albeit the observed ratios are 3.3 to 7.4 (McGinnity et al., 2008)."

Here you go:

Solfeo, thanks for the post... it's such a bummer, but does save me $200 a month on the oil I suppose. I'll save the CBD oil (I was taking the primo stuff grown locally) for after Tamoxifen then. I truly appreciate this advise, I can't really ask my doc y'know?

The Kailos site is really well done. I've ordered the test and emailed my doc asking her to sign off and reminding her I'm paying for this so hopefully she agrees. She seemed pretty open to all of my thoughts and frankly, I'd be intrigued to know if I was her and treating someone open to being more experimentive like Sol is... I will ask to do a 10mg if I'm high and 40mg if I'm intermediate. Not sure what I'd do if I'm poor, I'm still getting my periods regularly at 41.

Last question: I'm Vitamin D low. I had melanoma 6 years ago and simply stay out of the sun. I take a supplement, but clearly 2000 IUs is not enough. Any suggestions? I don't take K, could that be why I'm not getting the D absorbed? Could this be a protein metabolising thing as well?

Ok, that was more than a few questions. Solfeo, have you done any research on turmuric and melatonin in relation to inhibiting CYP? I have my list of vitamins I was planning on taking and it seems to be getting smaller. I'm bummed about the CBD.

My Vitamin D was nice and high when I was diagnosed, but when I started exercising more in the sun I was afraid of taking too much and lowered my dose. That caused around a 40 point drop. I'm back to around 70 now from taking 4000IUs 5 days per week (I try to give my body a break from supplements on the weekends).

When it comes to supplements and cancer and especially supplements and tamoxifen, you're going to find very little definitive proof of what is safe or effective. The science always conflicts and most of the research never reaches human clinical trial stage. The best you can do is read everything out there and then decide how much risk you're personally willing to take. I was a big supplement user before the diagnosis and I was really bummed by how much I had to eliminate when I started tamoxifen (note none of it prevented the cancer). I almost always err on the side of caution. I guess the right answer is to ask your doctor, but they don't usually know that much about supplements and interactions. Even my naturopath, although he is very well educated about supplements in general, had no idea about any of this CYP2D6 stuff. He was constantly telling me to take something that might interfere with tam. You should ask for your doctor's opinion but you really can't take anyone else's word on what is safe without evaluating the evidence for yourself.

Melatonin I believe is safe, and might actually enhance tamoxifen's action and prevent tamoxifen resistance. I take 5mg/day. I also try to sleep normal hours in complete darkness to promote my body's natural production of melatonin. There are studies you should read about the combo, easy to find in an internet search.

Curcumin is something I stopped taking when I started tamoxifen. A lot of people do take it with their doctor's blessing, and a lot of people are told not to because it might interfere with tamoxifen. There have been lab studies that showed an enhancing effect between the two, and that curcumin might also reverse tamoxifen resistance. However, those studies did not take metabolism in the liver into account. Curcumin inhibited CYP3A4 and reduced the levels of tamoxifen's active metabolites in a rat study, similar to what we have been talking about with CYP2D6 inhibitors. Curcumin is also a weak CYP2D6 inhibitor, which may or may not be a problem at that level, but no one is really sure how it behaves in humans. Test tube and rodent studies are not reliable either way.

I don't have a strong opinion about whether curcumin is safe or not when taken with tamoxifen, but the real truth is that no one knows for sure. Like I said, I always err on the side of caution. I will be taking it again when I switch to an AI.

shepkitty!!! I just now opened my insurance EOB and they also denied three of the tests for the reason "services not authorized." Shows my share as $2159.80. I don't know how this is possible when I got the pre-auth but it didn't list the tests individually, just said something like "unspecified molecular pathology approved." The list price Genelex gave me for the polypharmacy panel was only $1700 but they billed the insurance $2600 (each individual test separately) and said they wouldn't charge me more than the cash price if insurance wouldn't pay. Cash price quoted was $695.

I am headed for bed but I will be back to complain about this in the morning,

The more I research this issue the more I want to insist everyone get tested. This isn't just about Tamoxifen and BC, this is about saving babies lives as well. I was proscribed codeine after childbirth, if I was a rapid metabolizer of CYP2D6, I could have killed my baby.... How is it that we aren't testing people to find out their unique enzyme metabolizing rate?

Baby dies of Overdose due to Mother's ultrarapid CYP2D6 metabolism

Solfeo ~ Getting ready for my billing battle....

I have Medicare as my primary insurance and BC/BS as my secondary. The BC/BS is a full plan, not a supplement, that I am subscribed to as a retired federal employee. Each version of BC/BS has their own "rules of coverage", so my experience may not apply to all. I highly recommend anyone with billing issues to call their insurance plan first. Genelex is taking shortcuts in their claims filing to assure they get the highest dollar amount.

According to my BC/BS support person Medicare does cover a good portion of the testing. Genelex is required to accept the amount covered by Medicare as payment in full for the profiles covered. It appears that my claim to Medicare was not properly submitted causing them to deny paying for anything. The entire bill was sent to BC/BS. They will pay $1,706 for the tests if the provider is in their network. An in network provider must accept this amount as payment in full and cannot bill the patient for the difference. Genelex is not in network for my plan and billed BC/BS $3,759.00. BC/BS did pay them $706.54. They denied coverage for testing of Cytochrome P450, Family 2, Subfamily D, Polypeptide 6 (CYP2D6).......which is the main reason my PCP ordered testing as opiates/narcotics have no effect on my excruciating, never ending pain!

Allegedly Genelex offers payment assistance and grants for balances due. I am going to call them first and then work backwards if necessary to negotiate with my health insurance.

We need to know more about Kailos - ladies please share ASAP you get your results

Edited for typo

Lisey ~ will read and bbl. Go back to page 8 here and read forward. Really good information for those of us less sciencey ☺

I'm not particularly science-minded by nature. It took me over a month of constant reading to understand this stuff, but once you get it, it is actually pretty simple.

I don't want you to ever take my word for anything. I want you to learn for yourself because you will be a much better self-advocate once you know your game. That applies to everything involving your treatment. But I will summarize the situation in a fairly concise manner.

The science conflicts (you will see that a lot with BC). Some studies showed a connection, some showed no connection. The ones that have shown none have been criticized by the likes of the Mayo Clinic, which recommended further investigation. Current NCCN and ASCO treatment guidelines recommend against basing treatment decisions on testing, not because it has been found to be clinically irrelevant, but because of the conflicting evidence. Doctors are inclined to follow the guidelines and not deviate unless there is a very good reason to do so. Everyone needs to decide which side of this argument they feel more comfortable on because if you ask 5 people you will get 5 different opinions. Better safe than sorry is what I always say.

You're lucky your MO is on board, but you will run into other situations where you know something your doctor doesn't. I haven't met one I haven't been able to persuade yet - if not to agree with me then at least to go along to humor me. Either way works for me as long as I get the result I want. The struggle of trying to understand so many new things will be worth it when you can converse with your doctors on an equal level.

I don't envy you being so new to this but it does get a lot easier the more time passes and the more you know. Even the science gets easier to understand in general.

Lisey, I couldn't re-read every word but I'll tell you what I get from skimming back through the study in pre-menopausal women. The findings are much the same as prior studies in post-menopausal women and I think they were just trying to verify if there was any notable difference. CYP2D6 still seems to be the most important factor but they did also find lower endoxifen levels in women with BMI over 30. They conclude that testing of endoxifen level to identify who might benefit from tamoxifen dose adjustment, change of treatment to AI+OS, or supplementation with standalone endoxifen, might be a good idea if the results of this study are replicated.

Same stuff we have been talking about here would therefore be likely to apply to both pre- and post-menopausal women. Still not the final word on the matter.

shepkitty you are so kind. Good luck with Genelex. I talked to Anna in the billing department. She didn't even seem to be aware that the price list given to patients shows a much lower price for the full panels vs. the individual tests. I had to send her the test menu. I ordered the full panel but they are basing my share on the individual test prices because that is how they billed the insurance. She couldn't explain why they bill insurance almost $1000 over full list price. My co-insurance is so high because it is a percentage. Bringing up Kailos' much lower prices got me nowhere in terms of price matching. All she would say was that she didn't know anything about that. I'll probably have to take it to a manager before this is done.

She said they would appeal the denials to the insurance company but I couldn't get her to address specific issues that might have caused the denial. Their version of an appeal is to re-submit the same doctor's progress notes that were a part of the pre-authorization process to begin with, with no explanation. If their appeal is denied I can appeal it myself.

Fallleaves, it is ridiculous what people have to go through in this country to get affordable medical care and transparent pricing. I could rant about this subject for days. We are self employed and therefore responsible for the full cost of our insurance premiums. On July 1st that went up to over $1700/mo for the new plan year, from $1300 last year, with only 3 people in the family. Granted we used more services in the last year, but we have been paying through the nose for over a decade, and with our usual preference for natural medicine the insurance company is way ahead financially. They also re-set our deductible and max out of pocket mid-calendar year, that had already been satisfied, so we have to pay that twice in 2016 and then again in January for 2017. I need to keep costs down or go bankrupt but I can never find out how much something is going to cost beforehand.

Anna at Genelex did call me back a short time ago to let me know she called the insurance company to try to straighten this out. I think that is more than they usually do so apparently I did get through to her on some level yesterday. Of course they gave her the runaround too! There are 2 different insurance companies involved because the main insurer contracts with another insurer for out of state claims, and they both told her they have nothing on this claim and each blamed the other. I said, how do they not have it when they partially paid it? Unnecessary bureaucracy!