Drug Reponse - Tamoxifen (Nolvadex) Activation

In order to be effective, tamoxifen must be activated by liver enzymes

Tamoxifen is widely and effectively used to prevent the recurrence of estrogen receptor positive breast cancer. Most of the protective antiproliferative effects are not due to tamoxifen itself. They are due to tamoxifen metabolites created in the liver called endoxifen and 4-hydroxytamoxifen. The FDA strongly recommends using genetic information to guide treatment with tamoxifen.

The rate limiting step in the creation of endoxifen is the activity of liver enzyme CYP2D6. The CYP2D6 enzyme can be inherited as normally active, partially active, and totally inactive forms. Extra duplicated copies of active forms can also be inherited resulting in very rapid metabolism of tamoxifen to effective endoxifen. This establishes a gradient of ability to create endoxifen, and the level of protection against breast cancer recurrence.

Our test identifies your level of ability to create endoxifen from information on the copies of CYP2D6 that you have inherited, one from each parent. For more detailed information click here. We also test for the inherited forms of CYP2C19, most notably the *17 rapid form allow that is effective in creating endoxifen.

This information is more complete than tests offered by other companies. Insurance or your health savings account may cover the cost of this test.

While the genetic information provided by this test is expected to be extremely useful in determining your tamoxifen dose, deciding whether or not to use an alternate preventive medication, and your choice of other medications, in particular, anti-depressants some of which compete with tamoxifen for CYP2D6 activity, including paroxetine. No claim is made that all aspects of tamoxifen dose metabolism are investigated. It is absolutely essential that you and your doctor work together to obtain effective blood levels of tamoxifen.