CYP2D6 and TamoxifenTamoxifen is prescribed for the treatment of breast cancer. Some breast cancer cells require estrogen to grow which occurs through its binding to the estrogen receptor.
Tamoxifen and its metabolites bind to the estrogen receptor, but do not activate it and prevents further estrogen from binding. Therefore, breast cancer cell growth is blocked.
Tamoxifen can be considered a pro-drug that requires metabolism to elicit its pharmacological activity. Evidence now suggests that endoxifen, a secondary metabolite of tamoxifen, is most responsible for tamoxifen activity. In fact, endoxifen is 100 times more potent as an anti-estrogen than tamoxifen itself.
Cytochrome p450 2D6 (CYP2D6) is the main liver enzyme that metabolises tamoxifen to endoxifen. A number of commonly occurring gene variants have been identified in the CYP2D6 gene that significantly reduces the enzyme activity of CYP2D6.
Approximately 10% of the Australian population have gene variants in their CYP2D6 gene that results in little or no enzyme activity. These individuals are known as poor metabolisers. As such, poor metabolisers may not receive the full medical benefit of tamoxifen therapy since they have little capacity to metabolise tamoxifen to endoxifen.