CYP2D6 Test - No longer working

Lexislove - I am sorrry that you are struggling with this decision.  I am a bit bummed by all this new info since I was feeling pretty good about the whole "extensive metabolizer" thing - that is what I get for getting cocky I guess :-(

Anyway - all you can do is make a decision based on the information you have now - you and I, and everyone else here, doesnt have the luxury of waiting for them (being the researchers) to figure it all out.  So break it down....

If being a poor metabolizer means nothing and you get a ooph and start an AI - ok, what did you lose, what did you gain?

If being a poor metabolizer means SOMETHING and you dont get an ooph and start AU - ok, what did you lose, what did you gain?

Really - the first question is the only one that you would gamble with.  So here is what I think -

- switch to lupron and an AI.  That gives you time while continued research is going on.  If it turns out that poor metabolizer status means nothing you can still go back BUT you havent risked anything in the mean time.

lexislove,

I was in the gray area for my oncotype test, and I felt the same way about getting chemo... I thought that maybe I wouldn't need to get chemo, and my onc was fine with it... but I finally decided that I needed to go ahead and do the chemo...  I know, not the same thing. 

I think you feel better once you have made a decision... I know I did...   

I guess we can keep each other updated on the Femara....

Hugs

Harley

orande1

Raloxefine is also used to help prevent bc in women who are high risk, but have NEVER had breast cancer...

Personalized Cancer Care Off to Slow Start (Questions Tamoxifen CYP2D6 testing)

It was hoped some day that Genomic Analyses of cancer tumors would be able to identify in advance which patients will benefit from use of cancer drugs (clinical responders). A new draft report from the Agency for Healthcare Research and Quality (AHRQ) suggests that day is still a ways off.

The study looked at whether the presence of specific mutations in people who had breast and colon cancer and chronic myeloid leukemia determined if patients would respond to expensive new drugs commonly used to fight the diseases. Only in colon cancer did the mutation matter and in that case, while it ruled out the effectiveness of drug therapy, the relevant mutation only appears in a small percentage of cases.

In the finding most likely to cause controversy, the AHRQ report found there was "no consistent associations" between breast cancer patients with the relevant CYP2D6 polymorphism and the outcome of tamoxifen therapy, whether as primary treatment or in as post-operative adjuvant therapy. Estimates vary, but anywhere from 10 to 40 percent of women have the gene variant of CYP2D6 that is believed to slow the metabolism of tamoxifen and make it less effective. A number of companies sell a $300 test that can show if women have the allegedly telltale CYP2D6 polymorphism.

As is often the case, the 13 studies identified by the systematic review didn't contain enough data to draw definitive conclusions. "Most studies were relatively small and thus underpowered to detect what would be a plausible effect size for the modification of response to tamoxifen by a single polymorphism," the report noted.

Numerous studies in recent years have noted that colon cancer patients with the KRAS mutation do not respond to epidermal growth factor receptor inhibitors like cetuximab (Imclone Systems/Bristol Myers Squibb's Erbitux) and panitumumab (Amgen's Vectibix). The Food and Drug Administration, the European Medicines Agency and the American Society of Clinical Oncology have issued guidelines suggesting patients with the mutation shouldn't be given the drugs.

The AHRQ-sponsored review confirmed that finding. "Patients with KRAS mutations were less likely to experience treatment benefit, compared to patients whose tumors were wild-type for KRAS mutations," the report said. About 20 percent of patients have KRAS mutations, which generally signal a more virulent form of the disease.

Chronic myeloid leukemia is one of the great success stories for targeted chemotherapy drugs and imatinib (Novartis' Gleevec) has been a godsend for patients with CML since it came on the market a decade ago. But resistance is growing, and at least two similar drugs are now on the market, dasatinib (Bristol-Myers' Sprycel) and nilotinib (Novartis' Tasigna).

Some mutations of the BCR-ABL1 gene make the cancer resistant to imatinib (Gleevec), which is designed to block the action of the hyperactive tyrosine kinase receptors in people with CML. But don't look to any tests currently on the market to determine what they are. The review of 31 studies found that "the presence of any BCR-ABL1 mutation does not appear to predict differential response to treatment in CML patients treated with imatinib-, dasatinib- (Sprycel), or nilotinib- (Nilotinib) based regimens."

Indeed, the report said there is "no evidence that presence of any BCR-ABL1 mutation can differentiate response to tyrosine kinase inhibitor therapies."

"It is possible that pharmacogenetic (how our inherited genes affect the way we respond to drugs) testing and the subsequent use of targeted therapies will add cost without producing clinically meaningful improvements in patient outcomes," the report said.

http://www.ahrq.gov/clinic/ta/pharmgentest.pdf

Source: Gooznews on Health

There are some challenges in the development and practical use of pharmacogenomics. Many doctors now do not widely practice pharmacogenomics when treating patients since the field is still new.

Pharmacogenetic testing is also expensive, and insurance plans may not cover the costs of available tests. Researchers are working to develop more efficient and less expensive testing methods.

Although federal legislation has been passed that makes it illegal for companies and insurers to discriminate against people based on their genetic information, some ethical, legal, and privacy issues remain unresolved, which may affect the continued development of pharmacogenomics.

Hi revkat,

The SOFT trial is looking at either A: Tamox alone, B: Ovarian supression + Tamox or C: Ovarian supression + AI.

My onc asked if I wanted to participate in the SOFT. I declined, because I wanted to take the OS and Tamox. Now, Im kind of wishing I did say yes.

After finding out my poor metabolizer status, I have since stopped taking Tamox. I have not taken any antihormone in 3 weeks. Im planning on starting up with Femara next week.

This whole cyp2db is a p-a-i-n in the you know what. Somebody needs to get to the bottom of all the ?'s before young woman, like myself, go and remove their ovaries to switch to an AI.

Does anyone know if Parkinson's drugs such as Requip pose similar problem as SSRIs?

Apologies for key near R and Y making no impression!  Very good info, ladies.  I finish rads Wednesday Feb. 10 and see med onc March 1.  I expect [bad key]amoxifen because of severe bone loss in spine (I've been on Boniva infusion for a year).  

Update:

I see a gynecologist on the 10th to discuss an ooph. Oh, fun times....AND I start Femara the same day!

hlya - Please print this study Goetz was talking about to and take it to your physician - http://jama.ama-assn.org/cgi/content/abstract/302/13/1429 The study concluded that there was a very large difference in recurrence, but not a difference in survival. Personally, I think preventing recurrence is reason enough to think the test is worthwhile.

Other important studies confirming the importance of CYP2D6 include:

The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Goetz MP, Knox SK, Suman VJ, et al. Breast Cancer Res Treat 101:113-21, 2007

Conclusion: CYP2D6 metabolism, as measured by genetic variation and enzyme inhibition, is an independent predictor of breast cancer outcome in postmenopausal women receiving tamoxifen for early breast cancer. Determination of CYP2D6 genotype may be of value in selecting adjuvant hormonal therapy and it appears CYP2D6 inhibitors should be avoided in tamoxifen-treated women.

Relationship between CYP2D6 and estrogen receptor alpha polymorphisms on tamoxifen metabolism in adjuvant breast cancer treatment. Grabinski et. al., Proceedings of The American Society of Clinical Oncology 2006.

Conclusion: Tamoxifen (TAM) and its metabolites display large inter-individual variation with profound implications for breast cancer outcomes. Tamoxifen is hydroxylated to the potent metabolites, 4-hydroxytamoxifen (4-OH TAM) and endoxifen, by various cytochrome P450 (CYP450) genes including CYP2C9 and CYP2D6. The SULT1A1 gene is involved in the conjugation of 4-OH TAM. Tamoxifen's binding site is the estrogen receptor (ER). Genotype and ethnicity are significantly associated with levels of TAM and 4-OH TAM and may explain clinical variation in response to TAM treatment.

Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. Goetz et al. J Clin Oncol 2005 Dec 20; 23(36):9312-8.

Conclusion: In tamoxifen-treated patients, women with the CYP2D6 *4/*4 genotype tend to have a higher risk of disease relapse and a lower incidence of hot flashes, which is consistent with our previous observation that CYP2D6 is responsible for the metabolic activation of tamoxifen to endoxifen.

Clinical implications of CYP2D6 genotypes predictive of tamoxifen pharmacokinetics in metastatic breast cancer. Hyeong-Seok Lim, Han Ju Lee, Keun Seok Lee, Eun Sook Lee, In-Jin Jang, Jungsil Ro, J Clin Oncol 2007 Sept. 1; 25(25):3837-45.

Conclusion: CYP2D6*10/*10 is associated with lower steady-state plasma concentrations of active tamoxifen metabolites, which could possibly influence the clinical outcome by tamoxifen in Asian breast cancer patients.

CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. Jin Y et al. J Natl Cancer Inst 2005 Jan 5; 97(1):30-9.

Conclusion: Interactions between CYP2D6 polymorphisms and co administered antidepressants and other drugs that are CYP2D6 inhibitors may be associated with altered tamoxifen activity.

Werner Schroth, Lydia Antoniadou, Peter Fritz, Matthias Schwab, Thomas Muerdter, Ulrich M. Zanger,Wolfgang Simon, Michel Eichelbaum, and Hiltrud Braucholfgang Simon, Michel Eichelbaum, and Hiltrud Brauch. J. Clin Oncol 2007 Nov.20; 25 (33):5187-93.

Conclusion: Because genetically determined, impaired tamoxifen metabolism results in worse treatment outcomes, genotyping for CYP2D6 alleles *4, *5, *10, and *41 can identify patients who will have little benefit from adjuvant tamoxifen therapy. In addition to functional CYP2D6 alleles, the CYP2C19 *17 variant identifies patients likely to benefit from tamoxifen

Hi Lexis - tough decisions!!! look forward to seeing more of you on the Tamox site ;-))

BEST luck

C

My main doc is my breast surgeon. He is the one who leads all. 

I did asked my onc if I can have that test, and he gave it to me. ( Was 650.00$)

Anyhow, I went back to my b surgeon last week. I gave him the results that I have 0 gene mutation ( Wide type) its called here in Montreal, and he was afterall very happy that I had the test. He also mentioned that its not officially standard in Canada,he still had to tell me that, but that he was now happy that I can sleep better with that test being an extensive metab.

LEXISLOVE.

I am not your doc, but here in Montreal at McGill my surgeon gave me the strong impression that it was a good thing to have that test. He cannot offer it to all women, because  women have to pay $$$$$ out og their own pocket.

But he was happy that I finally had the test.

((I was lucky, I got 80% back from blue cross. ))

but is it reliable?

Hi all,

Can anyone tell me how long it takes? Do they do it by testing your tumor tissue like OncotpeDX test? Been to two oncs and they don't believe in this but it does sound like a useful tool in the fight against cancer, why are they skeptics? CS

Thank you so much BCA for the info!

Hey Chasing, I had the Genelex test too.  Free of charge and my insurance actually called me and said that they were participating in a study and did I want to take it with my onc's permission.  I jumped at the chance.  I do not know about the actual reliability of the test and I will leave all that to figured out and discussed by all the experts but I came back a poor metabolizer and that was enough information for me to make decisions with.  I had an ooph and am on Femara and for someone many years from meno it was a sucky decision to have to make but staying on Tamox with the information that I had was an even worse decision.  I did not have them send me the results but let my onc tell me and then discuss my options with me.  I have had very few meno side effects and have lost weight.  I am not sure if the question over reliability of this test is just about the swab test or the blood test as well but I do know that they test for loads of things with cheek dna swabs and I liked that it was non invasive.  I was sick of all the needles.  If you have insurance I think they will help cover the costs.