The CYP2D6 Connection
Tamoxifen is a prodrug, which needs to be converted in the body to its active metabolite (endoxifen) to have its anticancer effect. The CYP2D6 enzyme plays a crucial role in this activation process. However, genetic variations in the CYP2D6 gene which encodes the CYP2D6 enzyme can significantly impact this activation process of tamoxifen.
CPIC Guidelines and Clinical Evidence
The Clinical Pharmacogenetics Implementation Consortium (CPIC) have published peer reviewed guidelines providing clinical recommendations for tamoxifen therapy1 based on CYP2D6 metaboliser status. The CPIC recommendations are based on evidence suggesting that patients with reduced CYP2D6 activity have lower endoxifen concentrations resulting in an increased risk of breast cancer recurrence.
Implementing PGx Testing
PGx testing can identify individuals with reduced or absent CYP2D6 activity allowing healthcare providers to make more informed treatment decisions regarding tamoxifen therapy. myDNA offers CYP2D6 PGx testing with our Multiple Category Medication Test.
Reference: 1. Goetz MP, Sangkuhl K, Guchelaar HJ, Schwab M, Province M, Whirl-Carrillo M, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy. Clin Pharmacol Ther. 2018.