Metabolism and Tamoxifen
As increasing attention is paid to individualizing cancer treatments and there is better understanding of selecting treatments based on genetic features of a tumor, there has been much investigation into Tamoxifen. As you know, Tam has been widely used for the treatment of hormone-positive breast cancer since the late 1970s. It is still the most commonly prescribed endocrine treatment, especially for premenopausal women.
A recent study by Dr. Susanne Briest and Dr. Vared Stears has gained a lot of attention. They explored the recognized impact that pharmacogenetics plays in Tamoxifen's metabolism, efficacy, and safety for a particular woman. Here is a quote from her recent article in Clinical Advances in Hematology and Oncology:
A large amount of data concerning the metabolism of tamoxifen has been recently reported. Although key tamoxifen metabolites were identified a number of years ago, only recently has their role in predicting outcome of tamoxifen-treated women been described. The metabolism of tamoxifen is clearly complex and involves a number of different enzymes. The function of these enzymes is determined by host factors, which are determined by genotypes or concomitant medication use resulting in varying expression and function. Only few findings have been published to date to describe the association of variant alleles in candidate genes and the outcome of tamoxifen treatment. The pharmacogenetic determinants affecting tamoxifen's side effects, adherence, and secondary benefits require further validation. The results of prospective trials and retrospective examination of existing study populations are highly warranted to allow for deeper insights into the genetic influence on efficacy and safety of tamoxifen and other endocrine treatments in breast cancer.
AIs are recommended instead of or following 2-5 years of tamoxifen in postmenopausal women, whereas tamoxifen is the drug of choice in premenopausal women. At this time, it may be reasonable to consider CYP2D6 genotyping for women who are candidates for tamoxifen monotherapy but for whom other standard treatments are available.
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