Tamoxifen, a type of hormonal therapy medicine is used to:
- reduce breast cancer risk in women who haven't been diagnosed but are at higher-than-average risk for disease
- lower the risk of breast cancer coming back (recurrence) in women diagnosed with early-stage, hormone-receptor-positive breast cancer
- treat advanced-stage hormone-receptor-positive breast cancer
Tamoxifen works very well for most people, but there are some who have a recurrence or have a cancer grow while taking tamoxifen. Doctors have been trying to figure out why this happens.
The body uses an enzyme called CYP2D6 to convert tamoxifen into its active form. About 10% of people have an abnormal version of the CYP2D6 enzyme, which may keep them from getting the full benefit of tamoxifen. You may want to ask your doctor about being tested for this enzyme abnormality if you're considering taking tamoxifen.
Still, CYP2D6 testing is controversial because several large studies found that an abnormal CYP2D6 enzyme didn’t affect tamoxifen’s effectiveness. Also, certain medications can block the activity of the CYP2D6 enzyme, including antidepressants known as SSRIs and SNRIs, as well as Benadryl (chemical name: diphenhydramine) and Tagamet (chemical name: cimetidine).
Now, a study by Canadian researchers suggests that lower vitamin D levels during winter months also may affect tamoxifen’s effectiveness.
Vitamin D3 helps the CYP2D6 enzyme work. Most vitamin D is made when an inactive form of the nutrient is activated in your skin when it’s exposed to sunlight.
The study was published in the May 2013 issue of Breast Cancer Research and Treatment. Read the abstract of “CYP3A4 and seasonal variation in vitamin D status in addition to CYP2D6 contribute to therapeutic endoxifen level during tamoxifen therapy.”
The researchers took blood samples from 189 women who were taking tamoxifen after breast cancer surgery and did genetic testing to see if the women had abnormal versions of several enzymes and genes, including the CYP2D6 enzyme. They also measured the women’s levels of the active form of tamoxifen, vitamin D3, and cholesterol several times throughout the study and recorded whether or not they were taking an SSRI or SNRI antidepressant.
The researchers found that from January to March, the women had lower levels of vitamin D3, as well as lower levels of the active form of tamoxifen compared to levels measured from July to September:
- levels of the active form of tamoxifen were about 20% lower than average in January to March
- levels of the active form of tamoxifen were 8% higher than average in July to September
This is the first study to suggest that low vitamin D levels may interfere with tamoxifen’s benefits.
While the results of this study are interesting, more research is needed to confirm that low levels of vitamin D may affect tamoxifen’s effectiveness. Still, you may want to talk to your doctor about this study if you’re considering tamoxifen treatment or are already taking tamoxifen.
It’s also very important to tell your doctor about ALL other medicines you take, as well as vitamins, supplements, and over-the-counter medicines. Your doctor can tell you if any of these other medicines or vitamins can interfere with medicine you’re taking to treat breast cancer or reduce the risk of it coming back.
Editor’s note: In 2018, the Clinical Pharmacogenetics Implementation Consortium, an international group of scientists that issues guidelines on the effects of genetic factors on reactions to drugs, issued a guideline on using CYP2D6 genotype information to make decisions about prescribing tamoxifen after surgery to treat hormone-receptor-positive breast cancer. The guideline strongly recommends that people with an abnormal CYP2D6 genotype that makes them less able to metabolize tamoxifen be treated with a different type of hormonal therapy, such as an aromatase inhibitor.