CYP2D6 ability to metabolize tamoxifen and recurrence
Comments
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Lisey, they sure are blue. Interesting. Keep us up to date. Don't worry about sidetracking. The genetics don't mean anything if we can't apply them. You are now applying the info. Fun isn't it
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Fascinating stuff...... Lisey, my BP is low like that, too - when I take it at home! In the dr office it shoots up by 30-40 points. Crazy but true.
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Hi Jennie, I did an explanation of "White Coat Syndrome" Here a few posts back I think. Check back
sassy -
Thought you all might find this article (it's a mouse study) interesting. I know Sas has gotten into the gut microbiota on other threads. It seems to tie in here, too.
Intestinal Flora Effects Drug Response
The research was conducted using three different groups of mice, an experimental group of germ-free mice which were free of intestinal bacteria since birth, a group of mice that had received antibacterial drugs for 5 consecutive days, and a control group of mice with naturally occurring intestinal flora. Researchers used proteomics, a large-scale analysis of proteins, to clarify changes in the amount of the proteins involved in drug metabolism and transport in the liver and kidney of the two experimental mouse groups.
"The most significant drug-metabolizing enzyme that decreased was cytochrome P450 2b10 (Cyp2b10)," said Professor Ohtsuki, who lead the research project. "Not only was the amount of the enzyme reduced nearly 96%, but the metabolic capacity of the drug in the liver was also reduced by approximately 82%. Cyp3a11, a similar type of enzyme was also reduced by about 88%. The human enzymes corresponding to these 2 enzymes, CYP2B6 and CYP3A4 are reported to be related to the metabolism of more than half of the pharmaceuticals on the market."
Additionally, the breast cancer resistance protein (Bcrp1), a protein that transports many kinds of cancer drugs, was reduced by more than 50% in the livers of both experimental groups. Antibacterial drugs are sometimes prescribed to treat and prevent infection caused by bone marrow suppression, a side effect of cancer drugs.
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Hi Falls, These little buggers, the health of the biome can mean if we live or die. Here's the link to the biome thread. Reading all the studies from the beginning isn't easy, but it explains allot. Plus, there are at least 6 cancers directing related to the polycyclic aromatic hydrocarbons. (PAH). Breast, testicle, vulva, prostate, and a couple more.
Then further in the reading there is an article about how the gut microbes change the intestinal wall and allow for crossing into the circulatory system. These bad bacteria are call endotoxins. They wander around in the body causing all kinds of trouble. In the mouse study, the endotoxins change certain cells in the liver that impair glucose metabolism.
Previous to these studies circulating endotoxins were associated with illness. Now it's known that they cause problems, but are not overtly perceived i.e temp, illness. But can create illness over the long term.
https://community.breastcancer.org/forum/73/topics/832722?page=1
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Thanks for posting the link to that thread, Sas! Your recall of all the details is so much better than mine. I definitely need to re-read everything in there.
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Oh Falls just huge hugs, when you read the initial article about the contact with the "tribe" where the researchers went in and tested everything. EVERYTHING. Then relealizing they have no taxomy(sic) to put the bugs into. That they well be studing it for years how to create categories and names. If you follow the thread , I was on a bread crumb trail.....It was such a great learning. But I couldn't find any one that wanted to go on the trail with me. As you know studies can be so bleeping hard to read. So many don't read the whole studies. So. frustrating, because we then depend on an interpretation.
Just like the day to day press, a study can be interpreted by a reviewer. We were doing Toradol and I was doing the Microbiome at the same time. I physically was ill after both b/c I put too much time into them. Then I got into politics.
Now I'm off most everything. It wasn't healthy.
But I so dearly would love you to study the microbiome stuff on the weight thread. From beginning to end. It is the future. We have so screwed it up. This whole thing of disinfecting everything is only going to lead to more superbugs.
If you look at the last two posts on the weight thread. What the kidney transplant folks ought to be doing is what the folks are doing with the C-section moms. I have been meaning to call the kidney guy and tell him to look at the C-section research. Just haven't gotten to it. Rather than antibiotics, they ought to be inoculating recipients with the donors biome.
Yes, that seems a stretch, but we --science made so many moves against bacteria in the last century, we made great strides. Then what happened, Superbugs. We MUST learn more about them and how we are commensal. Cuz in the end if we are not respectful of their power to survive, it put's our survival into peril.
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Bacterias aren't bad, we just don't know how to live with them.
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I know that sounds like the most bizarre statement in our recent history or history, but they are an organism that is adaptable and will survive. We can learn from them, we can learn how they can promote wellness or illness. Random killing only weakens us not them. They will evolve. Resistance. They will win unless we recognize the stupidity of trying to kill them.
Fight random antibiotic therapy
OMD, I just became a radical
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Ha-ha, Sas, I never pictured you as a microbiome radical! I think you are right, though, about the power of bacteria for good and bad. We are just scratching the surface on something that affects so many different facets of health. I will go back into the thread (and it'll be like the very first time, because my memory is crap!) Hope you are doing well!
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Ladies, question for you... I've read that melatonin can help Tamoxifen... as an ultra -rapid metabolizer (who has no SEs at all in the 6 weeks I've been on it)... Do you think I should take melatonin? JohnSmith just posted that new studies show that melatonin is effective in helping stop ER+ stem cells. https://community.breastcancer.org/forum/73/topics/700674?page=1#idx_15
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A few seconds ago sas-schatzi wrote:
Folks I think John's link should be posted around in the threads you frequent.
1.Reason is most here have sleep problems.
2. It is a naturally occurring in the body
3. we need to use any thing that gives us an edge.
My personal experience with it is I used it for several years after BC @ the 10mg level along with Ativan. I had horrible insomnia. My ER+ path report said unfavorable outcome in two places. Always wondered why I haven't met'sd yet. Now 7 1/2 years.
I keep wondering if there was "something" I was doing that was helping?
Recent research is keying in on other things other than standard chemo drugs we need to keep these on our radar and make the decision whether they are reasonable to add to our regimen.
We all know it's still a crapshoot. I find that word the most disgusting word in the dictionary. So, this is an emphatic statement.
John reposting on my usual threads. Thanks for all the research you do.
18 hours ago JohnSmith wrote:
New article: Pre-clinical models reveal that Melatonin reduced proliferation of breast cancer stem cells in ER+ tumors.
https://blog.cirm.ca.gov/2016/08/24/sleep-inducing-hormone-puts-breast-cancer-cells-to-rest
TAGS: CSCs, transcription factor OCT4, encoded by the POU5F1 gene, mammospheres, Bisphenol A (BPA), MCF-7 cells -
WELL, poop there's more stuff about melatonin..........it's not as easy as it sounds
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SAS, what does that mean? should I be taking this stuff or not?
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Lisey for every damn article, we can find a counter article. I took it for years after BC. My stats are almost identical to your hormone stats. So, close they could be mine. Except, I was Oncotyp Dx 30 and grade 3. Write a post to John Smith from my last link. He's a mega researcher and he's seems to be studying it now. If he doesn't have an answer he will find one. I would take it, if it's working for you until more info comes in. Sleep is absolutely a huge factor in our wellness. Melatonin is naturally produced in the body. Make sure all supplements are from very reputable companies. There are some real shysters out there. I trust Solaray.
See what John has to say.
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Lisey, check in here at Bestbird's thread she has several positive links about Melatonin.
https://community.breastcancer.org/forum/8/topics/831507?page=2#post_4789872
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Sas, what have you read about melatonin that gave you doubts? I've collected a lot of studies and really not seen anything that would give me second thoughts. But lord knows there are a gazillion studies out there....
Here's the one (it's a rat study) that indicated melatonin could help reverse tamoxifen resistence:
Circadian and melatonin disruption by exposure to light at night drives intrinsic resistance to tamoxifen therapy in breast cancer.
"Strikingly, our results also showed that melatonin acted both as a tumor metabolic inhibitor and a circadian-regulated kinase inhibitor to reestablish the sensitivity of breast tumors to tamoxifen and tumor regression. "
http://www.ncbi.nlm.nih.gov/pubmed/25062775
(Dauchy, 2014)
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Hi Falls, Not sure what it was. It was not a lengthy post, but included the link. Then lost internet connection and lost the post and the site of the link b/c it was submerged. UGH. But just as I said to Lisey we can find papers that are for and against any subject.
I talked here for eons to myself essentially b/c I believed that the future was understanding individual genetics of metabolism. I figured eventually, more publishing would go on. It has. Genetics are playing into everything.
Jelson started the thread, my guess with the same belief. It has been proven about many individual drugs or classification of drugs.
What is still in the friggen wind is cost coverage. Which is totally crazy b/c of pure economics. Cost benefit ratio. The cost of care weighed against the benefit of providing a direct benefit that reduces cost.
The economics of drug cost versus benefit without knowing value outcome except based on SEER stats that only show improvement over decades. Here's a good economic term----Sucks.
Then we the chosen few(sarcasm), jump at any straw in the haystack that may give us an edge, just end up with dust up our noses. Sorry, that's my kind of a metaphor from childhood of jumping into the hay in the barn. Allergic ever since. It was a choice. No one else had a reaction. There was a bunch of us. WHY me. Why did we all do the same thing and I ended up a mess that day, with a life long allergy.
It's like this with cancer. We make choices, seems like the right thing, we hope the right thing, also, we may choose to not to do the supposed right thing. On to Metformin and Melatonin for me. There is good and bad written about both.
Lot's of Laughs, going to continue the wine........................
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I think you will eventually be vindicated and CYP450 testing will become mainstream. It makes economic and health sense NOW! Sometimes I think they are so busy looking for the magic bullet, they don't use the information we already have to our best advantage. All the hoopla about "personalized medicine" and still no testing for drug metabolism genetic polymorphisms? Stupidity.
Enjoy that wine, Sas, you've earned it!
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So I got the results of my Kailos tests, have not had a chance to dissect and even try to understand it all. And too tired to even try right now. All's I can say is that I'm going to be very interested in what my MO has to say about the results. The final results page that lists all the different medications ect, shows Cytoxan which is one of my current chemo's (I've currently done 1 of 4 TC's) show's I have an increased risk of toxicity. Will check back tomorrow to see if anyone has any input or thoughts on this. Email has been sent to make sure my MO can see a copy of the report. Got it as I was headed out of town on Friday.
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Sensi ~ Hey Grrrrl! This genetics stuff is fascinating. Biology and Chemistry are not my strengths; this has been kind of like being back to school. Don't panic yet over anything you have read in your report. Think of the results as being more of a suggestion than a certainty. Good that you gave your MO a heads up that there may potentially be some problems with your chemo. Do you go back in Monday for another treatment? I think I would call in the morning to make sure he sees the report. There are others here who are way more knowledgeable who will chime in and advise. Let us know what happens. Hoping everything works out 🐶
Edited to add....
Post your results here if you can. You can scan the page and save it to your computer as a jpeg and post it as a picture. Or just take a picture and post it.
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Hey All,
Interesting thoughts on the melatonin. I started taking it only 8 months ago....after I was done with Tamoxifen. Since my initial DX in early 2013 I've been stable. I have also been trying to be proactive by taking 500 mg of Metformin daily, MegaRed Krill Oil and mega doses of Vitamin C. Wish I knew for certain if this all has contributed to my stability.
My interest in CYP2D6 has been to do with the metabolizing of pain meds. Opiates are substrates and in theory bind to the enzyme to work faster. I am a normal metabolizer but have not had relief from opiates. I did have an excellent response to Tamoxifen. I had hoped to use the genetic testing to try to figure what pain meds might help me. My Neuro Onc had kinda burst my bubble in July when he told me that phenotypes, genotypes and in particular CYP2D6 were too poorly understood to be of any real use for treatment and medication. What the testing indicates and what a person's response is can be completely different. All he could offer was Sas's paint ball therapy - throwing stuff at my pain until we find what sticks. Major disappointment to say the least.
My PCP is a DO and brilliant. I worked on some theories of my own, discussed them with him and he added and improved to what I had come up with. So..............
My pain is from extensive bone mets with bone on bone and bone on nerve pain. Much pain in surrounding soft tissue as well. I've been on all the "big guns" as far as opiates/narcotics. No relief, only nausea and vomiting. I have been taking the maximum daily dosage for Tramadol and Fioricet. I also take low doses of Valium for spasms at bedtime and pain distress during the day as needed. I don't tolerate NSAIDs well and use ibuprofen for inflammation sparingly.
Earlier on this thread, it was mentioned that there was a theory that if one did well on codeine then that person would do well with Tamoxifen as they are both CYP2D6. I did very well with Tamoxifen but failed to have any relief using hardcore opiates. I can't remember the last time I was given codeine for pain but way back when, I did get relief from it. Fioricet works for me but isn't strong enough to handle all my pain. There is a version of it that has codeine in it. I asked PCP about it. He thought codeine might possibly have a "less is more" effect for me. Instead of changing my Fioricet, he added a script for liquid codeine. The liquid gives more control over the dosing and because it is separate, the effects will be easier to identify. If the codeine is not a good drug for me, I can discontinue it without interfering with my Fioricet. In pill form, codeine uses acetaminophen as a carrier to aid in absorption. Acetaminophen is already an ingredient in the Fioricet; too much is bad for the liver. The liquid codeine uses guaifenesin as a carrier. Guaifenesin is used in testing for a person's ability to properly metabolize Tamoxifen.... Everything seems to come full circle.
I have been taking the liquid codeine for two weeks now. It hasn't made me vomit yet and does give a short term boost to the Fioricet. I have also been taken Robaxin with nice results. Thanks to BestBird for recommending Robaxin in her MBC Guide and to JazzyJuneBug for sharing her success with it.
My questions:
If charting how we metabolize medications is not the solid answer, is it better to look at the medications and the pathways they use?
Can we get better results by charting the medications, our "real world" results and then comparing new medications to what we already personally know?
Why isn't guaifenesin more widely used as a carrier for other opiates in either tablet or liquid form? Would it prevent the n/v from the stronger opiates? Would those drugs work better?
Soo much to ponder............
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Hey guys, sorry for disappearing. I have started law school and it's crazy busy!
I got my Kailos results a few months ago and it confirmed what I already know. It's important to note that it's not 100% accurate. For example, it lists my valium response as "may be slow to wake up from sedation" but actually none of the benzodiazapine family work at ALL on me. Pretty much all of the responses are that the drugs don't work as intended, with a few here and there that might.
I had a 2nd opinion with another onc today, who reconfirmed that there is no way to tell if the AI inhibitors are working. I just am not happy with this answer
However, she suggested that perhaps doing an early BCI test might give me some direction. Still, I don't know if it will indicate whether or not AI's will even work correctly on me!Anyway, I'll try to catch up with this thread when I get the chance, but got to study now!
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Wow, McClure77, congrats on starting law school! What a whirlwind year this must be. Hope you have a great time learning the law!
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Hey Fallleaves...have you seen the studies about Feverfew and tamoxifen? I am sure you can find them better than me, but its something to look into!!
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No, Geewhiz, I haven't...but now you've gotten me curious!
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I just had my first endoxifen test, along with FSH and estradiol, to decide if I'm going to stay on the doubled dose of tamoxifen. The endoxifen takes a few days so I don't have that back yet. My FSH was postmenopausal in February, and it remains so today. My estradiol, however, seems to have skyrocketed! It's way above range even for an ovulating premenopausal woman (the time of the month it is highest). I don't know how this is possible to have menopausal FSH and very high estradiol. My last period was 6 months ago in April and I hadn't had one before that since Sept 2015, so 1 period in the last 13 months. I am the same age my mother was at menopause.
The last time I had estradiol checked was in August 2015, while I was still menstruating regularly, and it was only 294 mid-cycle, which was in the upper range of normal. I was also morbidly obese. Right now it is 513, which is significantly above range for any time of the month! According to the lab the highest it should ever get is 398 during ovulation. I am definitely not ovulating.
I vaguely remember someone on the boards saying that their doctor told them tamoxifen was probably the cause of her high estradiol test result. Does anyone know anything about this? My doctor didn't say anything about it and I don't see him until Monday. Needless to say I'm having a little freakout.
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solfeo---Might have been me who mentioned the high levels. My levels were in the 700 range the last time I was checked before my hysterectomy. I completely freaked out when I picked up a copy of my results so the nurse made my gyn take some time to talk to me. He reassured me that it was totally normal having high levels while on Tamoxifen. I have no idea why this happens or even if he's correct, but he's supposed to be one of the best gyns in my area and he was a rock star when he did my hysterectomy! Barely any pain and I was totally back to normal within 8 weeks so I trust him implicitly. Maybe you could call your nurse or something just to double check but I think if it was an issue, they would have already called you. My doctor was definitely watching me closely at the time as I was developing a thickened lining with cysts and fibroids so I think if it could have been an issue, he would have told me...mainly because I can be an extreme worrier! Like world class worrier! And I love to research so when I saw my numbers I had a complete panic. He put me totally at ease within minutes about it. Hope this helps!!
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Thanks lala, that's reassuring except for the hysterectomy part. I have read many of your posts but some of the details of your story escape me. Was the decision to get the hysterectomy based in part on the high estradiol? Did they think the estradiol level was a contributor to your uterine issues? The reason I decided to try the 40mg of tamoxifen to compensate for my reduced CYP2D6 activity (I am an IM) is because I want to avoid extreme measures like ovarian suppression and oophorectomy, considering that I am just counting down the months until I am fully menopausal. Just trying to get there so I can make a clean switch to an AI.
The purpose of the estradiol test was to determine my menopausal status so we know when it is safe to switch to an AI. If tamoxifen causes high estradiol and the doctor is aware of that, why would he be using that test as an indicator of menopause? How will we ever know when I am menopausal based on estradiol if the tamoxifen is elevating it? In my case I think the cessation of my periods is good evidence, but that is not guaranteed when tamoxifen can cause some women to stop having periods. Is the elevated FSH enough to make the determination that I am in fact menopausal?
Would love to hear opinions on all this before I see the doc because I don't necessarily trust him to know. There are no medical rock stars where I live. I frequently know more about the specifics of my disease and treatments than my doctors, who are very stuck on the standards unless I specifically ask for a more individualized approach, as I have done in response to my CYP2D6 test. -
I found this study: Associations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast cancer. But there is quite a bit I don't understand about the correlations. If anyone has an interest and time to read it I could sure use some help with interpretation. It may be of interest to everyone in this thread as they also looked at the role of various CYP450 enzymes.
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