Two large studies—one in the United States and the other in the Netherlands—reached different conclusions when they examined the risk of recurrence in women with breast cancer who took tamoxifen along with certain commonly prescribed antidepressants, such as fluoxetine (brand name: Prozac) and paroxetine (brand name: Paxil).
U.S. researchers found an increased risk of recurrence, while researchers from the Netherlands did not, according to presentations given at the 2009 American Society of Clinical Oncology Annual Meeting in May.
Several previous studies also show a link between decreased effectiveness of tamoxifen and the use of SSRI medicines for depression. Taken together, these results suggest that certain antidepressants may interfere with the effectiveness of tamoxifen in women with breast cancer.
Antidepressants known as selective serotonin reuptake inhibitors (SSRIs), including fluoxetine and paroxetine, are sometimes prescribed to treat hot flashes in women with breast cancer who are taking the hormonal therapy tamoxifen.
Some SSRIs work by blocking the body’s production of an enzyme known as CYP2D6, which plays a key role in helping the body process tamoxifen. Antidepressants that work in this way—also called CYP2D6 inhibitors—may lessen the effectiveness of tamoxifen in women who are taking the medications together. In turn, this could increase the risk of breast cancer recurrence. Researchers already know that women with a specific genetic mutation that blocks the CYP2D6 enzyme do not get as much benefit from tamoxifen.
Study Design and Goals
In the U.S. study (Aubert et al), researchers used a medical and pharmacy claims database to identify nearly 1,300 women with breast cancer who started taking tamoxifen between 2003 and 2005. They then divided the women into two groups: those taking tamoxifen alone (945) and those taking tamoxifen with a CYP2D6 inhibitor (353). The two groups were similar in age and underwent similar treatments before taking tamoxifen. The researchers compared their rates of recurrence within two years of starting tamoxifen.
In the Dutch study (Dezentje et al), researchers used medical records databases to identify 1,990 women with breast cancer who were treated with tamoxifen between 1994 and 2006. Out of these women, 215 also used a CYP2D6 inhibitor during tamoxifen treatment, 150 of them for 60 days or longer. The study compared the two groups to determine whether women taking a CYP2D6 inhibitor experienced recurrence sooner.
Both of these studies are observational, a type of study in which individuals are observed or certain outcomes are measured but no treatment (or "intervention") is given as in a clinical trial.
In the U.S. study, Aubert and his colleagues found that 13.9 percent of women taking tamoxifen and a CYP2D6 inhibitor experienced a recurrence of their breast cancer within two years of starting tamoxifen, versus only 7.5 percent of women taking tamoxifen alone. The difference translates into a two-year recurrence rate nearly twice as high in the group taking both medications together than in the group taking tamoxifen alone. This led the researchers to conclude that CYP2D6 inhibitors can interfere with the effectiveness of tamoxifen.
In the Dutch study, Dezentje and his colleagues did not find an association between CYP2D6 inhibitor use and breast cancer recurrence in women treated with tamoxifen. Among women taking a CYP2D6 inhibitor and tamoxifen, 13.3 percent had their cancer recur during four years of follow-up, versus 14.6 percent of women who took tamoxifen alone or used a CYP2D6 inhibitor for less than 30 days. This difference is small and not statistically significant, meaning it could have been caused by chance.
What Does This Study Mean for Me?
If you take both an SSRI antidepressant, such as fluoxetine or paroxetine, and also take tamoxifen, speak with your doctor about the potential interaction between them. Your doctor may advise switching either to another type of antidepressant or another form of hormonal therapy.
If you are postmenopausal, you may be able to switch to an aromatase inhibitor, a hormonal therapy that is not affected by CYP2D6 inhibitors. In addition, make sure your doctor knows about all the medicines you take, since there are some other medications that are CYP2D6 inhibitors.
Clinical depression is a serious condition, so do not stop taking your antidepressant without consulting your doctor. Many other treatments exist for depression, including medicines that do not inhibit CYP2D6.
R.E. Aubert et al. Risk of breast cancer recurrence in women initiating tamoxifen with CYP2D6 inhibitors. 2009 ASCO Annual Meeting. May 2009. Abstract CRA508. J Clin Oncol 27: 18s, 2009.
V. Dezentje et al. Concomitant CYP2D6 inhibitor use and tamoxifen adherence in early-stage breast cancer: A pharmacoepidemiologic study. 2009 ASCO Annual Meeting. May 2009. Abstract CRA509. J Clin Oncol 27: 18s, 2009.