Related Gene(s): CYP2D6
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 that inhibit these enzymes (eg, concomitant drugs), 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. Our 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 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 Tam for at least 3 months or until the steady state is ready.
CYP2D6 genotype of 17 variants is also available and should be ordered the first time blood is drawn for metabolite testing for optimal interpretation.
- Blood: 5 mL in sodium heparin tube (green top). Minimum 0.5 mL (0.2 mL plasma). 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 or until the steady state is ready.