Tamoxifen is a pro-drug metabolized by the liver to active metabolites. The protein in the liver responsible for some of this metabolism is the cytochrome p450 enzyme CYP2D6 (pronounced "sip two dee six").  

Across populations, CYP2D6 protein alleles can have different genetic variants that impact their ability to metabolize tamoxifen and other medications. The different alleles can produce four different metabolism phenotypes: ultrarapid, normal, intermediate, and poor metabolizers. The poor metabolism phenotype has been shown to reduce tamoxifen metabolism to its active metabolite, increasing the risk of treatment failure.

The Clinical Pharmacogenetics Implementation Consortium (CPIC) is a group that evaluates the evidence for the use of pharmacogenetics and then develops clinical practice guidelines.  For tamoxifen, extensive guideline information can be found at: https://cpicpgx.org/guidelines/cpic-guideline-for-tamoxifen-based-on-cyp2d6-genotype/ a reference maintained by CPIC.

Here is a video that reviews the CPIC guideline for tamoxifen: https://www.youtube.com/watch?v=0sb9J4GziyE 

At UCHealth the use of pharmacogenetics when prescribing tamoxifen will occur in patients who meet the following conditions:
1) Provided a blood or saliva sample to the CCPM biobank, consented for the return of their results, and this sample has undergone genotyping OR the patient is being seen in a clinic which is currently using pharmacogenetic testing as part of standard care (e.g., the UCHealth GI Oncology Clinic).  
2) Are prescribed tamoxifen.

For patients enrolled in the biobank, this process takes a minimum of 4-6 weeks but may take several years. Therefore, results will not be available at initial presentation if a patient has not previously enrolled in the biobank.

If you are a provider AND your patient is a CYP2D6 poor metabolizer, an inline medication warning will appear if you attempt to prescribe or refill tamoxifen in UCHealth's EHR. If the inline medication warning is visible, links to resources will be listed for your reference. There is patient education text available for UCHealth providers to use in discharge paperwork or the after visit summary (AVS).