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Are Your Cancer Patients Receiving the Full Benefits of Tamoxifen? When
your breast cancer patients tell you they feel fine on Tamoxifen,
that's good, right? Maybe not. Patients with certain genetic variants
may not receive the full benefit of Tamoxifen, because they poorly
metabolize the drug.
On
Oct. 18, 2007, an FDA panel recommended relabeling Tamoxifen to state
that poor metabolizers have an increased risk of recurrence and testing
is available.3
Know Before You Prescribe With Iverson's Tamoxifen Response PanelThe
Iverson Tamoxifen Response Panel is an easy-to-administer test that
identifies 8 unique genetic variants in the CYP450 2D6 gene (*2, *3,
*4, *5, *6, *9, *29 and *41A) that may cause patients to poorly
metabolize the drug. These variations can cause differences in the
metabolism level of Tamoxifen as well as in the effects of drug
therapy. Who Should Be Tested?
- Women for whom Tamoxifen may be prescribed as breast cancer prevention or treatment.
Understanding the Genetics
Cytochrome
P450 enzymes are a family of functional proteins encoded by 60 genes.
They play a crucial role in drug metabolism. Almost every drug is
processed by some of these enzymes.
CYP450
2D6 is a metabolic liver-enzyme that biotransforms approximately 25% of
drugs known to be metabolized by CYP enzymes. 2D6 is involved in the
metabolism of xenobiotics and is responsible for more than 70 different
drug oxidations.
Tamoxifen
acts by binding to estrogen receptors in the body and blocking the
action of estrogen, functioning as anti-estrogen. It is primarily
metabolized by cytochrome P450 (CYP) enzymes, and can be considered a
pro drug that requires metabolism to bring forth its pharmacological
activity.
Inherited
differences in these metabolic enzymes affect the risk of breast cancer
recurrence in women receiving Tamoxifen therapy. Patients with variant
forms of the gene CYP2D6 may not receive the full benefit from
Tamoxifen because they poorly metabolize the drug into its active
metabolite 4-hydroxy-tamoxifen, a minor metabolite of Tamoxifen.1,2
The Iverson Tamoxifen Response Panel can detect 8 significant genetic variants of CYP450 2D6: *2, *3, *4, *5, *6, *9, *29, *41A.
Frequently Asked Questions
Why should I order the Iverson Tamoxifen Response Panel for my patients? Our
test will allow you to better determine individual treatment by letting
you know when a patient has genetic variations that can cause poor
metabolism of the drug. I'm not a geneticist. How can I interpret the test results? Our Iverson Personalized Report will
clearly show whether your patient carries any of the tested-for
variations that can affect Tamoxifen metabolism. If you need more
information, our genetic counseling service is available to help you.
References
1.
Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM,
Li L, Araba A, et al. CYP2D6 Genotype, Antidepressant Use, and
Tamoxifen Metabolism During Adjuvant Breast Cancer Treatment. Journal
of the National Cancer Institute. 2005;97(1):30-39.2.
Blue Cross and Blue Shield Association Technology Evaluation Center
(TEC). CYP2D6 Pharmacogenomics of Tamoxifen Treatment. Technology
Evaluation Center Assessment Program. 2008;23(1):1-32.3.
Phan, Mimi T., Pharm. D., R.Ph.; Venitz, Jürgen, M.D., Ph.D. Summary
Minutes of the Advisory Committee Pharmaceutical Science, Clinical
Pharmacology Subcommittee [meeting transcripts]. 2006 Oct 18-19 [cited
2008 Oct 16]. Available from: http://www.fda.gov/ohrms/dockets/ac/06/minutes/2006-4248m1.pdf |
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Tamoxifen Facts
- Tamoxifen is the most commonly prescribed treatment for breast cancer and has been used in patients at high risk for breast cancer.
- Efficacy of Tamoxifen therapy is affected by inhibitors including other prescription drugs as well as variations in the CYP2D6 gene.1,2
- Genetic variations within the CYP2D6 gene determine the metabolic rate at which Tamoxifen is converted to endoxifen. Lower levels of endoxifen are believed to decrease the effectiveness of Tamoxifen therapy.1,2
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