According to the results of a study conducted in the United States and presented at the 2009 annual meeting of the American Society of Clinical Oncology (ASCO), certain types of antidepressants may interfere with tamoxifen (Nolvadex®) effectiveness. In contrast, a study conducted in the Netherlands and also presented at ASCO found no such effect.
Tamoxifen is a hormonal therapy used in the prevention and treatment of breast cancer. Inside of the body, tamoxifen is converted to its most active form— endoxifen—by a liver enzyme known as CYP2D6.
Some people have inherited gene variants that are linked with lower levels of CYP2D6 activity. Studies suggest that people with these gene variants may derive less benefit from tamoxifen. Drugs that inhibit CYP2D6 may also reduce tamoxifen benefit. CYP2D6-inhibiting drugs include certain drugs used to treat depression or hot flashes, such Prozac® (fluoxetine) and Paxil® (paroxetine).
Two studies presented at ASCO explored the relationship between CYP2D6-inhibiting drugs and tamoxifen effectiveness. The first study, conducted in the United States, involved 353 women who took both tamoxifen and a CYP2D6-inhibitor and 945 women who took tamoxifen alone. Among women who took a CYP2D6 inhibitor, the median duration of overlap with tamoxifen was 255 days.
Two-year risk of breast cancer recurrence was 13.9% among women taking both tamoxifen and a CYP2D6 inhibitor compared with 7.5% among women taking tamoxifen alone. This study suggests CYP2D6-inhibiting drugs may reduce tamoxifen effectiveness.
In contrast, another study presented at ASCO did not find a relationship between CYP2D6 inhibitors and tamoxifen effectiveness. Conducted in the Netherlands, the study involved 1,990 breast cancer patients treated with tamoxifen. A total of 150 used a CYP2D6 inhibitor for 60 days or longer during their tamoxifen therapy. The risk of breast cancer recurrence in these women was similar to the risk in women who either did not use a CYP2D6 inhibitor or who used a CYP2D6 inhibitor for less than 60 days. The researchers note, however, that relatively few women in this study used both tamoxifen and a CYP2D6 inhibitor. This may have limited their ability to detect an effect.
Although questions remain about the link between CYP2D6 inhibitors and tamoxifen effectiveness, women who are taking tamoxifen are advised to discuss with their physician any other drugs they are taking. It’s also important to be aware that not all antidepressants are CYP2D6 inhibitors. Women who are taking tamoxifen but require treatment of hot flashes or depression may wish to consider an option that does not inhibit CYP2D6.
Aubert RE, Stanek EJ, Yao J et al. Risk of breast cancer recurrence in women initiating tamoxifen with CYP2D6 inhibitors. Presented at the 2009 annual meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. Abstract CRA508.
Dezentje V, Van Blijderveen NJ, Gelderblom H et al. Concomitant CYP2D6 inhibitor use and tamoxifen adherence in early-stage breast cancer: a pharmacoepidemiologic study. Presented at the 2009 annual meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. Abstract CRA509.
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