Web Seminar: Pharmacogenetics in the Practice of Medicine
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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 (Selective Serotonin Reuptake Inhibitor) such as fluoxetine, paroxetine and high doses of sertraline or any of the more than 200 other medicines that inhibit CYP2D6 activity.
Does Insurance cover the testing?
Most insurers including Medicare are now consistently covering pharmacogenetic testing in many diagnostic situations including history of adverse drug reactions or lack of response to medication, pain management, cancer management, and management of many co-morbid conditions. We are currently only able to bill insurance for CYP2D6, CYP2C9, and CYP2C19. Testing of CYP1A2, 5HTT, NAT2, UGT1A1, DPD, and VKOR are also available, but only at a self-pay rate. CPT codes and preauthorization instructions are provided on the Physician Referral Prescription form if you would like to confirm eligibility in advance. For self-pay rates, call 800 523-3080. A patient safeguard program is available for patients without insurance or whose insurance will not cover the testing.
How do I order testing?
Simply complete the required prescription information on the Physician Referral Prescription form, hand it to the patient, and tell them to follow the instructions at the top of the page. When the patient contacts us, we will send the cheek swab collection kit with prepaid shipping directly to them. Alternatively, you can fax the form to 206-219-4000 with the patient's insurance information, mailing address, and phone number, and we will handle the rest. Buccal swab or blood collection kits with return shipping can be supplied on request at 800-523-3080
How do I interpret test results?
For every test ordered, we provide 90-days access to GeneMedRx Drug and Gene Interaction software with the patient’s genotypes already entered so you can determine the impact of genetics in the context of their overall medication regimen. GeneMedRx was primarily authored by Dr. Jessica Oesterheld, a recognized expert in drug interactions and coauthor of the top selling book, Clinical Manual of Drug Interaction Principles for Medical Practice. A short demo of the software and a free 30-day trial is available at www.GeneMedRx.com/demo. Interpretive Comments are also included.
How long does testing take?
Results are typically available within 10 business days.
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
Questions?
Call 800-523-3080 or email info@genelex.com.
Disclaimer: The content on this page is intended for healthcare professionals.
The text presented on this page is not a substitute for professional medical advice. It is for your information only.
Unless provided information expressly states that is was created by an MD or PharmD or cites another specific source, it was authored by Genelex employees that are not healthcare providers.
By Teresa Aulinskas, PhD Last Reviewed 8/20/10
