Tamoxifen testing

By: doort Date: 09-Feb-2019
<i>Tamoxifen</i> Therapy and CYP2D6 Genotype - NCBI Bookshelf

Tamoxifen Therapy and CYP2D6 Genotype - NCBI Bookshelf

Tamoxifen is widely prescribed for women with early-stage estrogen receptor positive (ER ), HER2-negative breast cancer following surgery. A 5- to 10-year course delays local and distant recurrence, prolongs overall survival, and reduces the incidence of contralateral breast cancer. Therapeutic drug monitoring based on tamoxifen metabolite concentrations accounts for the factors that impact tamoxifen effectiveness, including interindividual variation caused by CYP2D6 polymorphisms, liver disease, drugs, and patient adherence. It is a direct measure of the amount of active drug in the individual patient. Jager et al reported that increasing the tamoxifen dosage increases the amount of active drug in patient plasma. Clinical cutoffs for tamoxifen and its metabolites are not yet fully established. Data from Madlensky et al show a marginally significant reduced risk of breast cancer recurrence in patients with an endoxifen concentration in the upper 4 quintiles relative to the lowest quintile (HR=0.74; 95% CI, 0.55-1.00). Your body processes (metabolizes) tamoxifen more slowly to the more active form your body can use. Recommendations vary based on different types of breast cancer, the medications you are currently taking and your response to these medications. Talk with your healthcare provider about choosing a medication that may be the best option for you. Only health care professionals, and those you have given permission, may view your genetic test results. If you are receiving care at another medical facility, we suggest you share this information with your other health care providers. Your health care provider may suggest you take a different medication. Genetic variation in Tamoxifen is a medicine that blocks the effects of the estrogen hormone in the body. It is also used to reduce the risk of developing breast cancer in those who are at high risk.

Breast cancer treatment - Understanding Animal Research

Breast cancer treatment - Understanding Animal Research

Systemic tamoxifen has been the standard approach for reducing risk of recurrence in women with estrogen receptor (ER)–positive early-stage breast cancer for more than 40 years. Long-term data have demonstrated that the use of tamoxifen reduces recurrence and mortality by more than 30% in both premenopausal and postmenopausal women, regardless of the use of systemic chemotherapy. Aromatase inhibitors (AIs), such as anastrozole (Arimidex) and exemestane (Aromasin), have been proven to be as effective as, or superior to, tamoxifen. AIs have been utilized as initial adjuvant therapy, as sequential therapy followed by 2-3 years of tamoxifen, or as an extended therapy following 4.5-6 years of tamoxifen. Tamoxifen is metabolized via CYP2D6 into endoxifen (4-OH-N-desmethyl-tamoxifen), its primary active metabolite. Multiple investigations have identified genetic variants of CYP2D6 that can affect its activity, which in turn affects the metabolism of tamoxifen. The proficiency with which CYP2D6 metabolizes tamoxifen was assumed to be associated with the specific variant of the gene that an individual possesses, on the basis of studies that were conducted in breast cancer patients taking selective serotonin reuptake inhibitors (SSRIs) to relieve hot flashes. This testing can assist with customizing drug therapy by providing metabolic activity information that may explain patient drug responses relevant to CYP2D6 genetic variability. The cytochrome P450 (CYP450) enzymes metabolize many drugs. Individual genetic differences of cytochrome P450 activity can result in the total absence of metabolism to ultrafast metabolism of certain drugs. This assay does not detect other variants in the CYP2D6 gene that may affect metabolic activity. The metabolism of drugs is also influenced by ethnicity, diet, and other medications. All factors should be considered prior to initiating new therapy. This testing does not rule out the possibility of variant alleles in other drug metabolism pathways.

<strong>Tamoxifen</strong> Drug Interactions and Genetics -
Tamoxifen Drug Interactions and Genetics -

What medications may interact with tamoxifen, what is the mechanism, and what drugs may be used instead? How can genetics influence tamoxifen effectiveness? Learn about the CYP2D6 pharmacogenomic test that predicts how your genes will affect your body’s response to tamoxifen.

Tamoxifen testing
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