Dec 7 2010
While the medical community continues to debate the benefits of CYP2D6 genetic testing for women on the breast cancer treatment tamoxifen, patients using the medication are anxious to have the tests. According to a new survey of more than 700 women with breast cancer currently taking tamoxifen, almost 80 percent of respondents would choose to have a genetic test that determines CYP2D6 genotype, yet only 14 percent of these women have been tested. CYP2D6 is an enzyme that influences how well the body processes tamoxifen into its more active form.
“It is encouraging to see the high level of patient awareness of antidepressant drug interactions with tamoxifen”
Several studies suggest that women determined to be "poor" or "intermediate" metabolizers of tamoxifen due to a CYP2D6 genetic variation may experience a higher cancer recurrence rate than those found to be "normal" metabolizers. Other studies, however, have not established a connection between CYP2D6 genetic variation and tamoxifen treatment outcomes. New research on the topic will be presented at the upcoming San Antonio Breast Cancer Symposium on December 9th.
"As a clinician, these data tell me that our patients want more discussion on the pros and cons of emerging science, in this case CYP2D6 testing, even if we don't yet have definitive answers to all of their questions," said Dr. William J. Irvin Jr. of the University of North Carolina, Chapel Hill, an oncologist and expert on CYP2D6 metabolism who also helped design the survey.
The survey also found that more than two-thirds of respondents (68 percent) were unaware that commonly used over-the-counter (OTC) medications (including sleep aids and allergy medicines containing diphenhydramine or acid reducers containing cimetidine) may interfere with the metabolism of tamoxifen. Twenty percent responded that they take OTC sleep aids or stomach acid reducers two to seven times each week.
Further, the majority of respondents (58.5 percent) were aware that commonly used antidepressants - such as fluoxetine, bupropion, sertraline and paroxetine - may interfere with the body's ability to process tamoxifen. The most commonly used anti-depressant by respondents is venlafaxine which does not interfere with tamoxifen metabolism.
"It is encouraging to see the high level of patient awareness of antidepressant drug interactions with tamoxifen," Dr. Irvin said. "This reflects the change in the practice of medicine over the last five years as it has become more broadly understood that certain medicines inhibit CYP2D6 metabolism."
Survey Methodology
The survey, the first to explore patient awareness and attitudes regarding CYP2D6 metabolism and tamoxifen, was fielded over a three-week period in November 2010 among 791 women diagnosed with breast cancer who are currently taking tamoxifen. It was administered exclusively on Breastcancer.org, a leading online breast cancer information resource. The survey was sponsored by GTx, a pharmaceutical company which markets FARESTON 60mg (toremifene citrate) tablets, which is approved by the United States Food and Drug Administration for the treatment of metastatic breast cancer in postmenopausal women with estrogen receptor-positive (ER+) or unknown tumors.
Understanding the CYP2D6 - Tamoxifen Connection
Scientific researchers continue to explore how genetic differences and drug-drug interactions influence the body's ability to metabolize certain medications. For example, for tamoxifen to work properly in the body, it must first be metabolized in the liver by CYP2D6 into a more active form called endoxifen.
It is estimated that as many as 30 percent of Caucasians and 50 percent of both African Americans and Asians may have a genetic variation resulting in reduced activity of CYP2D6 and are "poor" or "intermediate" CYP2D6 metabolizers. These patients may not receive the same benefit from tamoxifen therapy as women with fully functional CYP2D6 activity. Additionally, several commonly used prescription antidepressants and OTC products such as sleep aids and allergy medicines are known to block the CYP2D6 enzyme, making it difficult for the body to process drugs such as tamoxifen. A more extensive list of medicines which may interfere with tamoxifen has been compiled by the Consortium on Breast Cancer Pharmacogenomics and can be found at http://medicine.iupui.edu/clinpharm/COBRA/Tamoxifen%20and%202D6v7.pdf.
To date, studies on the correlation between CYP2D6, tamoxifen metabolism and recurrence rates have been mixed. A 2008 Mayo Clinic study showed that women with breast cancer taking tamoxifen who have an inherited deficiency in CYP2D6 enzymatic function have a nearly fourfold higher risk of early breast cancer recurrence than women who do not have the genetic deficiency.
Several other studies have shown women treated with antidepressants which inhibit tamoxifen metabolism to a similar degree as "poor" genetic metabolizers have a higher cancer recurrence rate than women not treated with these antidepressants. However, other recent studies have not shown a difference in cancer recurrence in women taking tamoxifen based on CYP2D6 status or the concomitant use of tamoxifen and commonly prescribed antidepressants. Regardless, experts agree that women taking tamoxifen should avoid certain antidepressants and OTCs; however few recommend that women receive the CYP2D6 test.
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