Icahn School of Medicine at Mount Sinai
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Genetic Testing Lab

Test Catalog Biochemical Genetics Laboratory Tamoxifen Metabolites

Tamoxifen Metabolites

Test Description:
Tamoxifen (Tam), the anti-estrogen used to treat estrogen receptor-positive breast cancer is a pro-drug that is converted to its major active metabolites, Z-endoxifen and Z-4-hydroxy-tamoxifen (Z-4-OH-Tam) by various enzymes. Effective treatment depends on adequate Tam conversion to its active isomers. The plasma active metabolite concentrations vary due to common genetic variants in genes encoding the biotransformation enzymes, environmental factors (e.g., concomitant drugs) that inhibit these enzymes and compliance to the medication. CYP2D6 enzyme is critical in the conversion of Z-endoxifen; however, CYP2D6 genotype can only predict 30 – 40% of the variabilities of active metabolites. It is important that Tam metabolites be directly measured in blood for patients treated with Tam. Mount Sinai Genetic Testing laboratory is the only clinical lab that offers this service. The levels of Tamoxifen and its metabolites including 4-OH-tamoxifen isomers, endoxifen isomers and N-desmethyltamoxifen are measured by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Anti-estrogenic activity score (ASS) estimates summarizing the overall anti-estrogenic activity from all active metabolite concentrations are reported. The test is validated for steady-state metabolite concentrations with standard dose (20 mg/day) and is approved by New York State. Patients should be on a standard dose of Tamoxifen for at least 3 months and blood drawn before taking daily dose of tamoxifen.

CYP2D6 genotype of 17 variants is also available at Mount Sinai Genetic Testing Laboratory and should be ordered the first time blood is drawn for metabolite testing for optimal interpretation.

References:
1. Jaremko M, Kasai Y, Barginear MF, Raptis G, Desnick RJ, Yu C. Tamoxifen metabolite isomer separation and quantification by liquid chromatography-tandem mass spectrometry. Anal Chem 2010; 82:10186-93.
2. Barginear MF, Jaremko M, Peter I, Yu C, Kasai Y, Kemeny M, Raptis G, Desnick RJ. Increasing tamoxien dose in breast cancer patients based on CYP2D6 genotypes and endoxifen levels: effect on active metabolite isomers and the antiestrogenic activity score. Clin Pharmacol Ther 2011; 90 (4): 605-611.
3. Madlensky L,Natarajan L,Tchu S, Pu M, Mortimer J, Flatt SW, Nikoloff DM, Hillman G, Fontecha MR, Lawrence HJ,Parker AB, Wu AHB and Piece JP. Tamoxifen metabolite concentrations, CYP2D6 genotype, a nd breast cancer outcomes. Clin Pharmacol Ther, 2011. 89 (5): 718-725.

Specimen Requirements:
10 ml sodium heparin (green top) tube of blood drawn before patient takes daily dose of Tam. Protect sample from light, separate plasma immediately and freeze. Patient must be on standard dose (20 mg/day) of Tam for at least 3 months prior to testing.

Shipping: Ship overnight frozen on dry ice

Turnaround Time: 3 days

CPT Codes: 80299, 80500, 82544

Requisition Form and Consent: Tamoxifen Test Requisition [PDF]

Related Tests: P450-CYP2D6 (Tamoxifen Genotyping)