Low Levels of CYP2D6 Enzyme Affect Tamoxifen’s Effectiveness

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Tamoxifen is a hormonal therapy medicine used to lower the risk of breast cancer coming back (recurrence) in women diagnosed with early-stage, hormone-receptor-positive breast cancer. Doctors call tamoxifen used in this way "adjuvant hormonal therapy."

The CYP2D6 enzyme helps tamoxifen work in the body by changing tamoxifen into a form that is more active. Because of genetic differences, people make different amounts of the CYP2D6 enzyme. A study found that women diagnosed with early-stage, hormone-receptor-positive breast cancer who make very little or no CYP2D6 and were treated with tamoxifen didn't do as well as women with higher CYP2D6 levels. Other research has shown similar results.

The researchers looked at CYP2D6 levels in 1,580 women diagnosed with early-stage, hormone-receptor-positive breast cancer. All the women took tamoxifen as adjuvant hormonal therapy. The researchers identified three levels of CYP2D6 enzyme activity and production:

  • 46% of the women were "extensive metabolizers" with high levels of CYP2D6.
  • 48% of the women were "intermediate metabolizers" with lower levels of CYP2D6.
  • Nearly 6% of the women were "poor metabolizers" who produced little or no CYP2D6.

The researchers evaluated the medical histories of the women for 9 years after diagnosis, looking for differences in outcomes based on how much CYP2D6 the women produced. They found a number of differences, including a significant difference in the risk of recurrence:

  • 14.9% of extensive metabolizers had a recurrence.
  • 20.9% of intermediate metabolizers had a recurrence.
  • 29% of poor metabolizers had a recurrence.

Today, CYP2D6 gene testing isn't routinely done. Based on the results of this and other studies, CYP2D6 testing may help decide if tamoxifen is a good adjuvant hormonal therapy choice for a specific woman. For women with low levels of CYP2D6, an aromatase inhibitor might be a better hormonal therapy choice because aromatase inhibitors don't depend on the CYP2D6 enzyme.

The aromatase inhibitors are:

  • Arimidex (chemical name: anastrozole)
  • Aromasin (chemical name: exemestane)
  • Femara (chemical name: letrozole)

It may be some time before CYP2D6 testing is used to help guide hormonal therapy medicine choices. Still, you might want to talk to your doctor about this study if you're considering tamoxifen treatment or are already taking tamoxifen.

It's also important to know that some medicines can affect how the CYP2D6 enzyme functions and may reduce tamoxifen's effectiveness. These medicines include some antidepressants known as serotonin-specific reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Other commonly prescribed medicines such as Cardioquin (chemical name: quinidine), Benadryl (chemical name: diphenhydramine), and Tagamet (chemical name: cimetidine) can block CYP2D6 activity. Most doctors recommend avoiding any medicine that can affect CYP2D6 function while you're taking tamoxifen. If you have to take a medicine that may reduce CYP2D6 activity, you and your doctor should discuss hormonal therapy options that aren't affected by CYP2D6 activity.

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