Scientific researchers continue to explore how genetic differences and drug-drug interactions influence the body's ability to metabolize certain medications. For example, for tamoxifen to work properly in the body, it must first be metabolized in the liver by CYP2D6 into a more active form called endoxifen.

It is estimated that as many as 30 percent of Caucasians and 50 percent of both African Americans and Asians may have a genetic variation resulting in reduced activity of CYP2D6 and are "poor" or "intermediate" CYP2D6 metabolizers. These patients may not receive the same benefit from tamoxifen therapy as women with fully functional CYP2D6 activity. Additionally, several commonly used prescription antidepressants and OTC products such as sleep aids and allergy medicines are known to block the CYP2D6 enzyme, making it difficult for the body to process drugs such as tamoxifen. A more extensive list of medicines which may interfere with tamoxifen has been compiled by the Consortium on Breast Cancer Pharmacogenomics and can be found at medicine.iupui/clinpharm/COBRA/Tamoxifen%20and%202D6v7.pdf.

To date, studies on the correlation between CYP2D6, tamoxifen metabolism and recurrence rates have been mixed. A 2008 Mayo Clinic study showed that women with breast cancer taking tamoxifen who have an inherited deficiency in CYP2D6 enzymatic function have a nearly fourfold higher risk of early breast cancer recurrence than women who do not have the genetic deficiency.

Several other studies have shown women treated with antidepressants which inhibit tamoxifen metabolism to a similar degree as "poor" genetic metabolizers have a higher cancer recurrence rate than women not treated with these antidepressants. However, other recent studies have not shown a difference in cancer recurrence in women taking tamoxifen based on CYP2D6 status or the concomitant use of tamoxifen and commonly prescribed antidepressants. Regardless, experts agree that women taking tamoxifen should avoid certain antidepressants and OTCs; however few recommend that women receive the CYP2D6 test.

Source GTx, Inc.,