CYP2D6 ability to metabolize tamoxifen and recurrence

sas-schatzi

Cypher, the primary routes for all the AI's is through 3A4. This is what started me on my mission. My 3A4 is abnormal. I "failed" all three drugs cuz the s.e's.were awful. I'm an 3A4 intermediate metabolizer. My dose in using these drugs should have been reduced. But the scientific identification that the three's had an abnormality that was measurable wasn't known until 2011. I wasn't paying attention, by then I had quit them. The test for the 3's was made available by Genelex as part of their package in Sept. 2013. I got around to being tested in Jan., 2014. Both 3's came back abnormal. My 3A5 is rapid metabolizer. I copied the below from Genelex's web page. Sorry, no idea how to make it smaller print.

Aromasin

• Notes
• Alternates
• Mechanism
• Metabolism

SUBSTRATES

Mechanism	Path Size	Reference
CYP1A2	Major	62341
CYP3A4	Major	62342
aldo-ketoreductase	Major	62343
CYP2B6	Minor	62344

Arimidex

• Notes
• Alternates
• Mechanism
• Metabolism

SUBSTRATES

Mechanism	Path Size	Reference
UGT1A4	Minor	62306
Renal Excretion	Minor	62307
CYP3A4	Major	62308 |62309 |62310

INHIBITORS

Mechanism	Strength	Reference
CYP2C8	Weak	34291
CYP3A4	Weak	34292
CYP1A2	Weak	34293

Femara

• Notes
• Alternates
• Mechanism
• Metabolism

SUBSTRATES

Mechanism	Path Size	Reference
CYP2A6	Major	80296 |80297
CYP3A4	Major	80298 |80299

INHIBITORS

Mechanism	Strength	Reference
CYP2A6	Weak	45497 |45498

sas-schatzi

Cypher this is what my page with my genetics looks like. Don't know if this will work. It didn't copy exactly right, but close enough for you to get the idea of what I can learn from it. For some reason when I cut  and paste it's taking arimidex and putting it in with the active metabolite for Valium. Nope, couldn't get it to C&P and look the same as the web page. Since it's a password protected page. I rather not link it. But their's my report of my genetics.

Patient Factors
2C19 Normal Metabolizer, 2C9 Normal Metabolizer, 2D6 Normal Metabolizer, VKORC1 -1639 G/A, 3A5 Rapid Metabolizer, 3A4 Intermediate Metabolizer

sas-schatzi

Cypher LOL, Genelex sends little wallet cards with the info on it. I hand it to everyone. I can see by their reactions they are clueless as to what to do with the info. PCP and counselor use it b/c they are into it. 

When I had thyroidectomy, anesthesia glanced,grunted, and said "HUH-HUH"

I just had RAI-131 this week for Thyroid cancer. Had YouScript and RO all working on whether the RAI-131 went through either of the 3's . Which with 3A4, it would need to be reduced. Not sure if it went through 3A5, if they would increase the dose or just leave it be. 

Answer was Radioactive Iodine 131 went through neither. But they were all working to figure it out. Me too. Learned there's a WHOLE transport mechanism I knew nothing about. Methinks, I will leave it alone.

sas-schatzi

Bump

sas-schatzi

Just posted the following on the ASCO thread announcing new guidelines . I will bring the link to the topic back here

http://www.cancernetwork.com/survivorship/asco-gui...

If you are going to recommend a drug such as Duloxetine, then you are obligated to make sure the patients body can metabolize it. Duloxetine is primarily metabolized by CYP2D6 and CYP1A2.. You have not been known to support CYP testing in the past. Yet, you support targeted therapy or targeted molecular therapy for use and development of cancer therapies.

Why you don't support the one, and support the other is a mystery.

I coined the phrase main years ago Paintball Drug Therapy and Paintball therapy. It is the antithesis of Targeted Drug Therapy or Targeted therapy

Providing the NCI definition of Targeted therapy first, and then defining Paintball therapy

The term Targeted therapy which is defined by NCI as: A type of treatment that uses drugs or other substances to identify and attack specific types of cancer cells with less harm to normal cells. Some targeted therapies block the action of certain enzymes, proteins, or other molecules involved in the growth and spread of cancer cells.

Conversely, Paintball therapy is a type of treatment that uses drugs or other substances that are given as a general treatment without knowing if a patients individual genetic metabolism can allow the treatment to be successful i.e when a paintball is thrown how it splatters is unknown. A portion of the paintball may hit it's target, thus effective by chance. The splatter of the paintball is unknown. The effects, thus, may be harmful ranging from mild to major. Also, the Paintball approach to therapies may entirely miss the target or be substantially limited because the ability to metabolize is absent or limited.

How can you justify the support of targeted therapy for some drugs and use the paintball approach for other drugs.

If Paintball therapy or Paintball drug therapy enters the lexicon. I certainly would like to be credited with it's origin. 

sas-schatzi

Ah, the hubris of any age, LOL, Anonymity down the drain LOL . I do so like the phrase paintball therapy. I do hope it does enter the lexicon.

sas-schatzi

Kayb Your doc WHAT ...an ...IDIOT. He won't break protocol guidelines, but will take you off it b/c of QOL issues. NO in between. Dollars to donuts, he believes it's all in your head. 

The CYP testing could verify if your paths are normal. My 3's were abnormal----again found out this about the 3's  Jan 2014. 

All the AI's go through 3A4.  I quit all of the AI's b/c of QOL issues. 

I've used " Paintball" therapy phrase for several decades. Hope it catches on. The posting on ASCO was a perfect opportunity to define it in an open forum. 

Having a phrase that is the polar opposite or antonym is important in the word world, so it may have a chance, LOL.

I love Tsunami hot flash. It works. 

Take a look at the ASCO guidelines on Survivorship.   sassy

sas-schatzi

Kayb so right the testing for pathways is ahead of the clinical application b/c determination of individual genetics wasn't a criteria for involvement in the research. AND for example the abberration in the 3"s wasn't known until 2011. The fact that the work of 50% of aLL drugs go through these paths is huge for those people that have an abnormality in the 3's. The 2's weren't even fully understood when research on AI's was done. Tamox is so old, CYP was in the toddler phase of understanding

So, 

1. We have docs that are involved with writing Clinical Practice Guidelines i.e NCCN... that have minimal to no understanding of the CYP work

2. We have docs practicing on the direct care level that, also, have minimal to no understanding of CYP work, that will not vary from the NCCN guidelines

3. We have docs that are more willing to abandon a treatment that may be life saving, than go against the NCCN guidelines

4. We have patients that trust that their docs know what they are doing.

"Houston , we have a problem"

sas-schatzi

Sorry, I was so hard on your doc, I reread your post several times. He clearly was listening to you, but trying to stay within Guidelines. What the public doesn't understand is that when an organization is approved for recognition by another group,  is that the group /individual doc agrees to function by the external organizations rules i.e. guidelines. Loss of recognition as to following these guidelines is serious from many levels. Peer recognition and insurance reimbursement being two. Ability to partner with larger NCCN centers,  is the standard now.

To tired and hungry to continue further tonight. This thyroid cancer RAI-131 treatment has taken more out of me than expected.

Glad to see you Kayb  HUGS L&H&P's sassy

sas-schatzi

Finally remember why, I made up the words Paintball therapy. I used it to describe the prescribing of antibiotics without the benefit of culture and sensitivity testing. It was making me crazy, not remembering why I first used the phrase.

----------------------

Edit:5/14/2014-----came across a term in reading that is already accepted in medical usage for using a drug with out proper testing. I've not heard it before. It does however apply to how drug's are given without testing

The term is "best guess".

I'm an advocate for testing not guessing.

sas-schatzi

You may run screaming into the night, but it is a good demonstration of all the drug interactios
THE CYTOCHROME P-450 ENZYME SYSTEM

---

 

The term CYTOCHROME P-450 refers to a group of enzymes with are located on the endoplasmic reticulum.  These enzymes are of particular importance when studying drug biotransformation and drug metabolism.It is know that the gene for cytochrome P-450 has existed for more then 3.5 billion years.  This indicates drug metabolism by the P-450 system is a new and secondary role for these enzyme systems.The primary role for the P450 system seems to be one of metabolism and detoxification of endogenous compounds after they have been taken in by mouth in the process of eating.  This accounts for the high concentrations of these enzymes located in the liver and small intestine.The P-450 system can be altered by a number of mechanisms including inhibition and induction and can vary from person to person.
There are over 30 human P-450 isoenzyme systems that have been identified to date.  The major ones responsible for drug metabolism are the CYP1A2,  CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and the CYP3A5-7.

Knowledge of the P-450 system is critical in understanding drug metabolism and drug interactions.  Listed below are 3 links that will show 3 different tables:  The first table shows what cytochrome system is involved in the metabolism of various drugs (substrates).  The second table shows various drugs and the various cytochrome P-450 enzyme systems that either inhibit or induce that drugs metabolism.  Lastly the third table shows the various cytochrome P-450 enzyme systems and shows what drugs induce or inhibit the various enzyme systems.

Table 1 - Various Drugs and the P-450 Systems Responsible for Their Metabolism

Table 2 - Various Drugs and the Variuos P-450 Enzymes that Inhibit or Induce their Metabolism

Table 3 - Various P-450 systems and What Drugs Inhibit or Induce the Enzyme System

Table 4 - Drugs / Foods that Induce or Inhibit Various Cytochrome P-450 Systems and the Drugs that are effected by this Induction or Inhibition.

Footnote: this section copy and pasted from the following article. The links to Edmunds page says 2003. Old. But the point

http://www.anaesthetist.com/physiol/basics/metabol/cyp/Findex.htm

The links to Edmunds page says 2003. Old. But the point is the identified CYP path and then the drug interactions. One thing just scrolling fast, you will NOT look at Acetominophen the same way again. Interacts with lots of drugs.

 

 

 

Fallleaves

Interesting stuff, Sas. Reading through the last link, I thought the two paragraphs below were illuminating. If I understand correctly, you can not make a blanket assumption on how your body will metabolize various drugs based on knowing whether you are a high or low expressor of CYP2D6. I had thought if you had low functional 2D6 then you would not metabolize enough of ANY drug using that pathway for it to be effective (e.g. tamoxifen), but it looks like for some drugs it creates toxic levels, and for others it keeps the drug inactive. Very complicated.

"The explanations for the various polymorphisms are thought to be complex, but perhaps the most interesting is the high expression of CYP2D6 in many persons of Ethiopian and Saudi Arabian origin. 2D6 is not inducible, so these people have developed a different strategy to cope with the (presumed) high load of toxic alkaloids in their diet - multiple copies of the gene. These CYPs therefore chew up a variety of drugs, making them ineffective - many antidepressants and neuroleptics are an important example. Conversely, prodrugs will be extensively activated - codeine will be turned in vast amounts into morphine!

In contrast, many individuals lack functional 2D6. These subjects will be predisposed to drug toxicity caused by antidepressants or neuroleptics, but will find codeine (and indeed, tramadol) to be inefficacious due to lack of activation! Other drugs that have caused problems in those lacking 2D6 include dexfenfluramine, propafenone, mexiletine, and perhexiline. Perhexiline was in fact withdrawn from the market due to the neuropathy it caused in those 2D6 inactive patients unfortunate enough to be treated with it. Even beta-blocker removal may be impaired (for example, propranolol) in 2D6-deficient people."

sas-schatzi

Fallleaves, the importance of knowing your genetic status on these paths can be critical. For me when I had my 2's done and they were normal. I was surprised. I've had to be careful with meds for life long. When my 3's came back abnormal, that expained everything. 50% of all drugs go through the 3's.

Now getting the docs up to speed in knowing how to apply the knowledge is going to be work.  

sas-schatzi

This isn't genetics/genomics related, but you never know who may be reading that wouldn't see it someplace else.

Hi, popping in. I was posting with another member. I thought sharing the below information may be helpful to you .

The link www.needymeds.org is to a web site started by a Social Worker and a doc. It is a tricky site to use. The first page leads to a several hundred resource pages. But I think this first page, does not project the wealth that lies beneath. Be patient when following the links within the site. There are sections that are disease and drug specific. The specific page then links to lists of organizations that provide monetary or other types of assistance.

Register first and do the request for assistances form. Reason: the request for assistance form is filed. If you apply to 1 or 20 organizations/companies, the forms don't need to be repeatedly filled out.  The system is designed to pull information from the original form. There may be a few particulars that need to be added to a companies/organizations form.

All the pharmaceutical companies have patient assistance programs. All the drug manufactures are listed there

The other way to reach drug manufactures is 1. call the manufactuer patient assistance number(goolge keywords: drug name and manufacturer, then to webpage>>>patient assistance. Very time consuming.

There is so much more on www.needymeds.org. It took a bit of time to wander through the whole site. I've shared a telephone walk through with many friends and relatives. I even called healthcare facilities to tell them about this link.

For completeness, there are many ways to get financial assistance for whatever you need. There are organizations that will do things for you i.e volunteers that buy groceries, drive, install handrails, build wheelchair ramps.

How to find the info besides from the link above?  FIND the SOCIAL WORKER(SW).  It's there job to know these things   Talk to all of the following 1. cancer center SW,  2.hospital SW, 3. Insurance companies SW, 4. County SW. 5. church outreach leader.

I requested from my insurance carrier, a consult with a SW. That one appointment with the insurance carrier Social Worker, led to grants totaling $10,550. The meeting with the cancer centers SW, led to coverage of neulasta  for $4000.00.

sas-schatzi

Bumping, believe it or not nothing to soap box today LOL.

sas-schatzi

I won't be posting here for awhile. I thought I'd put together my major thoughts re: CYP testing.

Testing if left to the docs won't happen. We have to learn it, to save ourselves

I'm an advocate of testing for the 6 major players, and of any other players in the future that are shown to influence life with chemicals.

The testing is affordable with insurance. Insurance carriers  and docs should be pestered till they test.

I got so caught up in reading again, that I bypassed  statements that I meant to post here. Whew. This is hard stuff, but it's important.

Starting two weeks ago my PCP and I began to alter my drugs. It will be interesting to see if I have less  medication interactions and side effects.

We are looking to reduce drugs that use 3A4 and 3A5. Mine as you know are abnormal.

One drug choice is metoporol (2D6 only) will replace carvedilol/Coreg(many and 3A4). This will be started after  minimum 2 1/2 weeks off Norvasc.

Norvasc  uses 3A4 & 3A5. I am a 3A4- IM, I would need a reduced dose, 3A5--RM I would need an increased dose. Too confusing.  We took the easy way out, drug was deleted b/c of lower extremity edema (now improved). It's class of drugs are nortorious for causing lower leg edema and Norvasc is the worst.

The bottom line is I have a tool to evaluate the medicines going into my body. My hope is that the information explosion on this subject will be better used by all practioners. That testing for enzyme metabolism and using the knowledge to prescribe medicines becomes the common approach.

Taking a break sassy

Jelson

cp148 posted about folate. Ihatesnowihatesnow posted an article about it also, but it goes into a bit of detail about what goes on in the liver with folic acid.  Sounds like a metabolizing issue.

http://chriskresser.com/folate-vs-folic-acid

Headeast

Sas, I hope you keep posting. I just starting reading this thread and have to read it through from beginning to end. Don't want to miss any information given here. Thank you for your posts!

sas-schatzi

Baker, Hello ,  can't tell you about what oncologists are doing, but if you have read all the information, you know that the CYP testing IS the thing of the future. We can make it happen by demanding from our docs and insurers that they make it so (Pecard- LOL). This is going to be consumer driven to get it done. Not a person reading this has reached this stage in life without some strange thing happening with a drug.

If you have read my posts, particularly, starting around Feb 23rd 2014, I have chronicled my complications with drugs. You, also, know, I know my genetics for the 2's and the 3's. I'm a bit safer now. The reason I say "a bit", is now I have to get the docs to learn it. Greg Palewski who is a consummate researcher pointed out that ASCO wasn't recommending it. ( Greg if I misquoted you, PM me and I will correct this But The Onco's aren't knowledgeable about  the whole Cytochrome system. For example, Tamox is primarily metabolized by 2D6, but does go through some 3A4 metabolism. So, 2D6 can be tested, but if 3A4 is abnormal problems can occur.

Ironically, I have concluded that I am alive today because my genetics weren't known. Based on pathology, I had a very aggressive cancer. I was given the standard dose. It's pathway was through 3A4. For adjuvant therapy, my dose should have been reduced. This is based on my genetics as a intermediate metabolizer through that path. I had what's referred to as a relative overdose. Not enough to kill me, but almost did. Not the exact definition, but close enough. Then a second thing happened. The Hospitalist hung the wrong IV fluids when I went in to the hospital with a WBC of 1.5,  Neuts of  0.5, and a temp 104.8. He should have hung Normal Saline 0.9%. Instead he hung 0.45% , also, referred to as half normal saline. That put me into Acute Renal Failure(ACR).

Relative overdose + ACR = Circulating elevated drug level for longer than expected because of no kidney filtration.  The ACR was reversed by the proper fluids after the nephrologist evaluated the situation.

Important concept. Actually, if there was a decent science researcher reading this, it could be an avenue of research.

The problem is ACR is not always reversible. Thank God, mine did not become permanent Chronic Renal Failure(CHR), otherwise I'd be on dialysis.

Baker, I believe everyone should have their genetics done, but again the irony of  the lack of genetics and the doc screw up, are likely why I'm coming up to my 6th cancerversary in Jan.

 

Jelson

well here is something interesting, lets try and wrap our brains around this and figure how Roundup used extensively in wheat production might be impacting our ability to metabolize our breast cancer treatments (probably in addition to causing our breast cancer in the first place) http://www.thehealthyhomeeconomist.com/real-reason-for-toxic-wheat-its-not-gluten/

sas-schatzi

Jelson and kayb- Chit.

sas-schatzi

Oh BakerBaker---- No, I know what I know, and will say I don't know when I don't.  At first read, my reaction to your question was OH MY, over my head

Alteration by the metabolism from normal, alters how the drug is expected to work. The trails were done without knowing each persons metabolism through 2D6 and 3A4. Which I think, makes conclusions drawn in the trials a crapshoot. Hmmm not a proper scientific response, but if you think of it for awhile, you will understand my point. If my observation is valid, then none of the trial info is valid. Wow, that's messed up.

 For those that have their genetics done through Genelex, they have 1.  pharmacy staff that can work through with the doc on what should be done in other than normal. 2. the computer interface of applying the genetics to the specific drug being used is done. 3. computer also does a drug to drug interaction check based on the genetics. They have all bases covered.

No one else in the world has put the three together. This is an important concept for later as I attempt to respond to your 2 specific questions.

You're very specific questions. I'll work through what I can, but a better answer would come from a top flight researcher.

"#1.Tamoxifen is more effective especially for premenopausal patient. If test shows poor metabolizer, should the patient change to another drug?"

I am not the pro, but will say what I can.  

"Tamoxifen is more effective especially for premenopausal patient."  According to the trials and the approval by the FDA for this drug, this part of your question is true.  But as I stated earlier the genetics of the patients studied within the trials was unknown. Based on the fact that actual genetic metabolism is now available, in order to draw any conclusion how a patient responds, the subjects studied would have to be divided into each metabolism group. That's not been done.

Which leads to the second part of question #1 "If test shows poor metabolizer, should the patient change to another drug?". What I can say, is no one can answer that because it hasn't been studied. What can be done with any drug, is the dose can be altered. The unknown is: Is that altered dose effective. It hasn't been studied. Docs/Pharmacists may suggest that this is the way to do it because it seems logical, but it hasn't been studied.

Both your questions are amazingly challenging. I will say again, I'm not the pro. If the scientific method that is used in all clinical trials, is the accepted method determining effectiveness of a drug, your first question shows the vulnerability of the validity of the drug to accomplish what it was approved for by the FDA.

Getting a bit nervous about this long post getting wiped out. Will submit, then work on your second question

 

sas-schatzi

Second question:"2. If the patient gets severe side effects from Tamoxifen, does it normally mean she is strong /extensive metabolizer?"

If you accept what I'm saying in regard to the first question, then my answer is: this is unknown because it hasn't been studied.

BakerBaker, I think there is allot of people surmising how to treat with this drug, but it hasn't been studied. At first read, I didn't think I'd be able to answer your question at all. Now I'm amazed. It's a pretty right on response.

ASCO guidelines do not recommend the use of 2D6. Based on this discussion that makes sense. I'm going out on a limb here and raising the question. Is the recommendation for not using 2D6, based on the fact that they realize they don't have any data to support use of the drug b/c the trials didn't base the conclusions on how the study patients metabolized the drug? The problem that I have with that question is if it's true, it would seem that is incumbent upon the committee that approved the Clinical Practice Guidelines to inform the public of this.

GAWD bakerbaker, this is a kettle of worms. They only true answer is the trials need to be redone.

sas-schatzi

Oh kayb, thanks for the study, knew you'd come through.

Bakerbaker yup way above my head, but can read well enough that controversy is all over it. I agree with kay, take this to your doc.

Hopeful82014

Sas - I hate to impose on you but it's late and my eyes are fried, so I will

Do you know if the above applies to all AIs, particularly Femara?

Thanks for any help you care to provide - and for all you do on this site for all of us. I always know your posts are worth reading.

sas-schatzi

Hopeful What a very sweet thing to say. Greatly appreciated and will be remembered when someone goes for my jugular.

Re: AI's. Dunno is the final answer. It was so late last night trying to read the article that kayb brought. I have contemplated my response to bakerbaker.

She put two questions together that go to the heart of all research in this period. There is an uniqueness in this point in history and there are scattered pieces of thoughts through all the posts on this thread that I will try to bring together.

The research re:metabolism by in vivo(in the body) and invitro (in test tubes) has been going on for decades. The exact date of the beginning of each is irrelevant, but the acceleration of it was around 1950. Then every decade brought us closer to an understanding of how chemicals move through the body,  work before being metabolized or after, how some are not metabolized and excreted unchanged, and understanding how all the multiple chemicals introduced into the body from any route interact. The disciplines that need to be learned to do what that last sentence said are: Anatomy, Physiology, Chemistry of the body,  Chemistry of all chemicals external to the body, Physics, and Genetics.

The Human Genome project of the 1990's set the stage for the intergration of all the subjects above. The uniqueness of our time now, is we are at the advent of application of genetics to all the physical sciences. Prior to this present period science performed experiments, looked at outcomes, and developed conclusions. There was a turning point for how this was done in the late 40's. The steps of the Scientific Method were formalized, so, that all research in the world followed the same approach to whatever subject was studied. Accepted within the method, is that the outcome of a study is repeatable.  Now that we have genetics as a real versus theoretical tool, all future research will change to include the study subjects genetics at the beginning of the study. All study subjects will be grouped together. Only then can outcomes be predictable.

We know much about the major genetics, but new research is being published every day. The knowledge explosion at this time in history is a blessing and a curse. For us here, there are studies before the ability to use the known genetics and studies repeated after where known genetics were used. The article that kayb brought is demonstrating that concept. In reading that article they are saying that there shoud be retractions of studies because different alleles weren't considered. With the finding of the function(how it works) of a new gene, it will be utilized for future research. Then new research comes out and says whoa we've identified  a variations on that gene. An example, of this is 3A4 a one or two new alleles (variation of the gene) were verified in 2011. So, the research 3A4 is all invalid prior to that knowledge, because now there are two to three ways chemicals are metabolized through that path---not one.

Again restating the uniqueness of our time: identifying a gene, identifying how a gene works, and identifying  different copies (allele's) of a gene that changes it work-- how do we apply that knowledge to the patient. This may not happen all at once. Research doesn't stand still. In our case what drug do we use, how much, and how often today may be the standard and tomorrow is not the standard.. That again recognizes the uniqueness of our time.

Just when we think we have the right answer, new info comes along and causes the right answer to be questionable or wrong.

I think I referenced a quote from the editor of major scientific journal. When questioned about how much of what is published in his journal was true. His answer was "None of it", which was shocking to the interviewerer. The editor went on to say effectively 'What we print today, may be old tomorrow"(paraphrase)

Back to AI's. AI's go through primarily 3A4 without going back and doing a relook. There are the three metabolism alleles Im, N, and rapid. . Definitive studies would have to be done on each for an absolute answer to your question. But only 5% of the population have the variant. I'm one. It does suggest that the studies done on AI's have a greater validity rate than studies done on 2D6 b/c the allele variant rate in the population is much higher for 2D6.  2D6 has 5 variants versus 2. The increase in allele variants and the increase percentage of the presence of variants in the population  causes the results to be more questionable.

Hopeful, hope this all made sense sassy

sas-schatzi

Baker and Hopeful hope this doesn't muddy the waters. I took all three AI's. I choose to quit each b/c of S.E.'s. The pain was unbearable. I would love to see an AI study done that had a group of variant 3A4 Intermediate metabolizers and a normal metabolizergroup. When I quit Arimidex. I asked the doc if we lowered the dose could I take them. His answered makes sense as applied to the above posts. "No, there's no research to support doing that". That was in 2009. My 3's were tested in Jan, 2013.

 I'm surmising that a dose modification discussion with knowing my 3's are abnormal, would be given much more consideration now, even without research, rather that outright dismissal. Baker this  harkens back to your question. In the answer I gave you to the two questions in the previous posts, they  were the black and white answers that science demands. We now know my genetics. Even without having research to support a dose change,  it would be considered, because we now understand there is a difference in metabolism. This consideration of doing something different is within logical reason b/c we have some science behind it, this is the grey area of science.

Hopeful82014

Sas - thanks for your thoughtful reply. I'm looking forward to sitting down and giving it the time it deserves this evening.

In the meantime, should anyone 'go for your jugular,' I've got your neck!

sas-schatzi

rotflol hopeful, thanks sassy

Hopeful82014

It's the least I can do, Sassy.