Web Seminar: Pharmacogenetics in the Practice of Medicine
Tamoxifen Genotyping Research Summary
Recent research has shown that up to 35% of women with estrogen receptor positive breast cancer may fail tamoxifen treatment, because of drug interactions and their genetic make-up. The ability of these women to convert tamoxifen to the active compound endoxifen is compromised, resulting in greatly increased risk of relapse. DNA testing and careful analysis of overall drug regimens in these patients provides evidence that can be used to improve their chances of survival. With more than 500,000 women currently taking tamoxifen, this research has wide-reaching implications.
The Research
Tamoxifen is a prodrug widely used to treat, and as prophylaxis for estrogen receptor positive breast cancer. Out of the ~120,000 new ER positive breast cancer patients per year, 41,000 of whom will die, 42,000 are predicted to fail tamoxifen treatment because of 2D6 poor metabolizer phenotype (Jemail 2006). "Hot flashes," a common side affect, is typically treated with SSRIs, many of which are potent inhibitors of CYP2D6, phenol-converting intermediate metabolizer patients into 2D6 poor metabolizers, now demonstrated as crucial to the activation of tamoxifen to endoxifen. Endoxifen has a 100X greater receptor affinity than tamoxifen and is 30-100 times more effective (FDA 2006).
CYP2D6 genetically normal metabolizers also taking an inhibitor had 58% lower endoxifen levels and are likely to be in the group of ~35% of patients who don't respond to tamoxifen. CYP2D6 frank poor metabolizers, homozygous for *3,*4, *5, and *6, had endoxifen levels 26% of WT. CYP2D6*4/*4 PMs had a 3.12 hazard ratio for breast cancer relapse. Two year relapse free survival is 68% in patients with the 2D6 PM phenotype and 98% in Normal Metabolizers(Goetz 2005, 2007). This suggests that widespread genotyping and therapeutic drug monitoring could result in successful outcomes for many of the 35% of ER positive breast cancer patients who currently fail tamoxifen treatment.
Who Should Be Tested
The CYP2D6 test for tamoxifen is considered appropriate for postmenopausal women who are taking or considering taking tamoxifen to prevent the recurrence of breast cancer. It is especially important if the patient is also taking or considering co-administration with SSRIs.
The Testing Process
The process is simple. We send a blood collection kit in the mail, and you return samples to our laboratory by overnight courier. Results are typically available within 10 business days. Accelerated (STAT) four-day testing is also available.
In the News
Mayo study further confirms the importance of CYP2D6 for tamoxifen effectiveness building the case for genotyping and medication management. Click here to read the story.
References
Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin. 56:106-30 2006
http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4248B1-01-FDA-Tamoxifen%20Background%20Summary%20Final.pdf
Goetz MP, Rae JM, Suman VJ et al. Pharmacogeneticsof tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol, 23:9312-8 2005
Goetz MP, Knox SK, Suman VJ et al. The impact of cytochrome P4502D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat 101:113-121 2007
Ordering Tests
Now you can add another dimension to providing safer and more efficacious care to your patients by ordering DNA Drug Reaction Profiles for them. Call (800) 523-3080 for more information or to obtain collection kits, or visit
how to order for test requisition forms and sample requirements.
