Enzyme Determines Effectiveness of Tamoxifen Treatments
Researchers from the University of Michigan and the Mayo Clinic have performed a study showing an inherited gene that lowers levels of a key enzyme may indicate whether Tamoxifen treatments will effectively treat women with a common type of breast cancer.
Tamoxifen is a Selective Estrogen Receptor Modulator (SERM) therapy prescribed to treat estrogen receptor positive forms of breast cancer which comprise approximately 75 percent of breast cancer cases. The drug is designed to interfere with the patient’s estrogen so the cancer doesn’t return.
Genotype testing on 297 cancer patients revealed a gene variant which controls the CYP2D6 enzyme—an enzyme that helps metabolize Tamoxifen. The variant occurs in about 10 percent of women.
Based on these genetic test results, each patient in the study was assigned a CYP2D6 score. The data revealed that the higher a woman’s CYP2D6 score, the less likely she was to complete Tamoxifen treatments. The primary cause was the patients couldn’t tolerate the adverse side effects produced by enzymes metabolizing the drug.
In contrast, women who had lower enzyme levels didn’t fully metabolize the drug so side effects were reduced and more easily managed.
As the scientists point out, this presents an unusual paradox: the women most likely to benefit from Tamoxifen treatments are also the ones most likely to stop using it because their side effects are more severe.
Experts predict that genotype testing may one day be a common practice in medicine, but more research needs to be done before doctors can be sure the costly tests will improve patient outcomes. As the lead investigator of the study said,
“Overall, the results we’ve found have held up, but we’d like to see these results reproduced in a bigger study before we say every woman should go out a get genotyped.”
Dr James Rae
Department of Internal Medicine, University of Michigan
The AmpliChip® CYP450 test used in the Michigan-Mayo study was developed by Roche (OTC: RHHBY) and costs about $500. The product was approved by the US Food and Drug Administration in 2004.
Results of the study were presented at the San Antonio Breast Cancer Symposium held December 13-16, 2007.
Source: ABC News
Related Links: American Society of Health-System Pharmacists; PharmGKB.org
Related Video: What Do I Do After Tamoxifen? from Advances in Oncology
Related Audio: New Genetic Factors Found for Breast Cancer Risk from NPR
Tags: NOLVADEX®; hormones; pharmacokinetics; chemotherapy
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