Tamoxifen is a medicine used to treat and prevent certain types of breast cancer. It works by blocking oestrogen, a hormone that can help cancer cells grow. Around 7 out of 10 breast cancers grow in response to hormones like oestrogen or progesterone. For these cancers, hormone therapy is an important part of treatment. Tamoxifen has been used for decades to lower the risk of breast cancer coming back and to help prevent new cancers.
How does Tamoxifen work in the body?
Tamoxifen itself isn’t very strong. Once you take it your body changes it into a more usable form called Endoxifen. Endoxifen is much more powerful than Tamoxifen at blocking hormones that drive breast cancer. Taking Tamoxifen should therefore slow or stop the cancer growing or recurring. Tamoxifen is changed into Endoxifen by an enzyme in our liver called CYP2D6.
However, some people are carrying changes in their genetic code (DNA) that reduce how well the CYP2D6 enzyme works. If your body makes CYP2D6 enzyme to slowly, you may not get the full benefit from the Tamoxifen leaving you at a higher risk of your cancer recurring. There are also some other medications which can block the function of the CYP2D6 enzyme, further impacting on how effective the Tamoxifen will be. Understanding how your CYP2D6 enzyme works can directly influence how successful your cancer treatment could be.
Metaboliser Status of Individual | Frequency in Population | Impact on Tamoxifen Prescribing |
Poor metaboliser | 0.4 – 5% | Choose an alternative |
Intermediate metaboliser | 0.4 – 11% | Choose an alternative or increase dose |
Normal metaboliser | 67 – 90% |
Standard dose |
Ultra-rapid metaboliser | 1 – 21% |
How genetic testing can help
Everyone’s CYP2D6 gene is slightly different. These differences can affect how well tamoxifen is processed. How you metabolise medications cannot be predicted by your age, sex, ethnicity, or cancer type. Therefore genetic testing, known as pharmacogenomic testing, is the most accurate way to find out.
The Forensic Genomics Innovation Hub offers a pharmacogenomics test panel that can check your CYP2D6 gene and report your “metaboliser status,” which will indicate how well your body is likely to activate tamoxifen. This can be essential information for breast cancer patients who are prescribed Tamoxifen. It can also tell you if any of the other medications you might be taking could further affect your CYP2D6 function.
What your results could mean
Your test results can help your Doctor decide on the best treatment for you. In summary;
Other medicines that can interfere with how you process Tamoxifen include;
Antidepressants — They can block the CYP2D6 enzyme and lower the effect of Tamoxifen. Strong blockers include Fluoxetine, Paroxetine, Bupropion, and Duloxetine. Weaker blockers, such as Citalopram and Escitalopram, may still matter if your CYP2D6 activity is already low. Safer options, like Venlafaxine or Desvenlafaxine, are often used instead.
Why this matters
Knowing your CYP2D6 status can help your doctor choose the most effective treatment and avoid medicines that might reduce Tamoxifen’s benefit. This personalised approach can give you the best chance of lowering the risk of breast cancer coming back.
References:
What is pharmacogenomics?
https://www.sciencedirect.com/topics/medicine-and-dentistry/cyp2d6
https://www.breastcancer.org/treatment/hormonal-therapy/tamoxifen
https://go.drugbank.com/drugs/DB00675
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