CYP2D6 Intermediate Metabolizer, Tamoxifen side effects/benefits

I'm interested in any answers you might get here ... I was just tested (waiting on results) because I am *lacking* SE's! From what I've gathered from my MO, studies have not been done on varying dosages of Tamoxifen (the 20mg is the "gold standard) so if I was a high (w/terrible SE's) or low (essentially rendering the drug ineffective) -metabolizer, we wouldn't adjust the dosage, but instead look at alternatives to nip the estrogen (ie. suppress/remove ovaries & try an AI). I'm glad my MO decided to test me but I am nervous for the results ... very hopeful that it shows I'm metabolizing it just fine and am just a lucky one w/out SE's!

Good luck in getting more answers ...

I have wondered about this too because my side effects have been pretty mild. I didn't have chemo because my Oncotype was low, so I really need the tamoxifen to work. I want to ask for the test but my MO is stuck on the "standards" and right now the standard is still not to test. I don't see her again until March.

Always enjoy your posts JohnSmith. I have read a lot about it, and I think it might be overstating things to say it was deemed not clinically relevant, depending on what you meant by that. Most guidelines are not recommending it due to limited and conflicting evidence, but not because it has been proven to not be a factor. Here's a statement from the NCCN, from the link posted by MidLifeCrisis above:

Statement from the National Comprehensive Cancer Network (NCCN): "The cytochrome P-450 (CYP450) enzyme, CYP2D6, is involved in the conversion of tamoxifen to endoxifen. Over 100 allelic variants of CYP2D6 have been reported in the literature. Individuals with wild-type CYP2D6 alleles are classified as extensive metabolizers of tamoxifen. Those with one or two variant alleles with either reduced or no activity are designated as intermediate metabolizers and poor metabolizers, respectively. A large retrospective study of 1325 patients found that time to disease recurrence was significantly shortened in poor metabolizers of tamoxifen. However, the BIG 1-98 trial reported on the outcome based on CYP2D6 genotype in a subset of postmenopausal patients with endocrine-responsive, early invasive breast cancer. The study found no correlation between CYP2D6 allelic status and disease outcome or between CYP2D6 allelic status and tamoxifen-related adverse effects. A genetic analysis of the ATAC trial found no association between CYP2D6 genotype and clinical outcomes. Given the limited and conflicting evidence at this time, the NCCN Breast Cancer Panel does not recommend CYP2D6 testing as a tool to determine the optimal adjuvant endocrine strategy. This recommendation is consistent with the ASCO Guidelines."

Anyone with me in wishing there were more definites in the world of breast cancer research? I didn't ask for the test to begin with because I accept the guidelines and there are the studies that say it doesn't matter. That is reassuring. Doesn't stop that nagging doubt that in my situation I need to be better safe than sorry. Well, we all do, but it's such a matter of conflicting opinion what is safe or not.

Cubbie2015 - I love scientific discussion, I'm just not very good at it. I have read that before. Here's the synopsis.

Synopsis

In essence, our commentary addresses the pitfalls of retrospective pharmacogenetic research, which, in the case of the CYP2D6-tamoxifen relationship, has produced conflicting results that have caused a delay in resolution of a clinical management question that affects two thirds of women who are diagnosed with breast cancer. This underscores the need to consult existing pharmacokinetic/dynamic/genetic studies that provide critical information on the pharmacology of the drug under investigation before large pharmacogenetic studies are conducted, a position that has been previously expressed.³⁶ Given that alternatives to tamoxifen exist, the failure to resolve this question is particularly egregious in that the potential exists to deny women effective endocrine therapy. Given the inability of the published prospective-retrospective studies to resolve this issue to date, we conclude that a properly conducted prospective trial in the adjuvant setting is necessary to provide a definitive answer. However, we disagree with the comments of Rae et al¹⁷ and Regan et al¹⁸ that ongoing prospective clinical trials conducted in the metastatic setting (Eastern Cooperative Oncology Group E3108 [Tamoxifen Citrate in Treating Patients With Metastatic or Recurrent Breast Cancer] and European CYPTAMBRUT-2 [An Observational Study to Assess Response to Tamoxifen]) will provide an answer to the so-called CYP2D6 adjuvant question. This relates not only to their study design of enrolling patients with metastatic/advanced cancer, but the fact that patients with hormonally insensitive disease (aromatase-inhibitor refractory) are eligible for ECOG E3108, a population substantially different than that in the adjuvant setting. Therefore, until prospective, adjuvant trial data are available, it is our opinion that the current evidence is sufficient to accept the CYP2D6-tamoxifen pharmacogenetic relationship in postmenopausal women. However, it is clear that other host and tumor factors, besides CYP2D6, contribute to tamoxifen response/resistance. Researchers and clinicians should be encouraged to rigorously scrutinize the available pharmacogenetic, pharmacokinetic, and pharmacodynamic evidence to avoid drawing conclusions on the basis of potentially inaccurate data that could lead to the termination of research into a potentially promising biomarker.

I just wanted to let everyone know that the company Genelex that does cyp2d6 testing is good. They gave me a quote for what the price would be if my insurance didn't cover it and that is what it ended up being. It was $362. I did have to call them a few times when I got billed incorrectly and I was glad to have had emails proving the price they quoted me, but in the end the price was what they had said. I did need a doctor's presc to get the test, and the results were sent to the doctor, though I was able to call in and get the results myself as well. I hope this helps. As it turns out I have only one allele, not two, so I am able to take tamoxifen successfully but should be careful not to take other drugs (that are related to cyp2d6) at the same time. It was nice to have the peace of mind that the tamoxifen is working. If you have two bad alleles, you can take a drug called toremifene instead of tamoxifen. That is what my sister is doing.