What Affects Tamoxifen Response?

Changes in the gene called CYP2D6 may affect how a person responds to tamoxifen. How well tamoxifen works can also be affected by other factors, including other medicines and overall health.

CYP2D6

CYP2D6 is one member of a family of enzymes called "cytochrome P450." This gene makes an enzyme that converts one chemical to another. When you take a drug, it may need to be converted to other chemicals through a series of steps before your body can use it. CYP2D6 is involved in the metabolism of 20% to 25% drugs that doctors prescribe.

In this case, CYP2D6 converts tamoxifen to two other chemicals that have stronger effects than tamoxifen itself. These are called the active forms (metabolites).

How well CYP2D6 works is called its activity level. Genetic changes can affect the CYP2D6 activity level. These changes cause the enzyme not to work as well. When this happens, less of the drug gets turned into its active forms. With less active drug, the medicine may not have its full effect.

About 46% of women have normal or enhanced CYP2D6 activity. They metabolize the drug in the way doctors usually predict. This means that they should have a normal response to tamoxifen.

Up to 48% of women have one normal gene copy and one gene change, and up to 6% of people have two gene variants. They have reduced activity and they metabolize tamoxifen more slowly. They may not get the full benefit of tamoxifen. Having one or two variants has been associated with a higher risk for breast cancer recurrence. Other therapies, like aromatase inhibitors, may work better for these women.

CYP2D6 Variants and Ethnicity

The chance to have CYP2D6 gene variants is different depending on your ethnic background.

Other Factors

CYP2D6 gene changes alone do not explain all of the differences in how people respond to tamoxifen. There are other genes involved. These genes code for enzymes that are also involved in processing tamoxifen and its active forms in the body. There are also other factors, like overall health and other medicines, that change how people respond to tamoxifen. In particular, some antidepressant medicines can interfere with tamoxifen and make it less effective. You should discuss any medications that you are taking or plan to take with your physician. See the table below for a list of drugs known to be metabolized by CYP2D6.