Abstract
The concept of individualized therapy is intended to deliver the right therapy to the right patient at the right time. Personalization of treatment aims to shift health care from population based or empirical approach to scientifically tailored approach. Pharmacogenenetics use the genetic information such as DNA sequence, gene expression and copy number to explain the inter-individual differences in drug metabolism (pharmacokinetics) and physiological drug response (pharmacodynamics), to predict the efficacy and toxicity of drugs and to identify responders and non responders to a specific drug. Success of the personalized medicine depends on the identification of predictive biomarkers and development of accurate and reliable diagnostics. Tamoxifen is estrogen receptor antagonist. It is the corner stone therapy for breast cancer either in the adjuvant or metastatic setting mainly in patients with female hormone receptors positivity. Response to tamoxifen is affected by the genetic variation of CYP2D6. This cytochrome is responsible for tamoxifen metabolism to its active metabolite endoxifen. There is still no recommendation on the clinical utility of CYP2D6 genotype as biomarker to predict the treatment clinical outcomes in breast cancer patients. The reported data suggest that polymorphisms in CYP2D6 and ER genotype might be useful in selecting women who would gain the highest benefit from tamoxifen and those who are susceptible to adverse effects. For the time being the optimal strategy for individualization of tamoxifen therapy is likely to be the therapeutic drug monitoring. Pharmacists have a distinct knowledge and background about medications and have the ability to develop and lead pharmacogenetic programs. they have a fundamental responsibility and accountability to advocate for the importance and rational for implementation of pharmacogenetic testing, to set recommendations to optimize medication therapy based on test results, to conduct and participate in research that accelerate the application of pharmacogenetics to clinical practice and to educate health care professionals and patients. Given the uncertainties in this field management decision should be individual and based on patient possible risk, alternatives, preferences and the best available evidence.
Highlights
Tamoxifen pharmacologyTamoxifen is a hormone therapy belongs to the selective estrogen receptor modulators (SERMs) class of therapy
Pharmacists have a distinct knowledge and background about medications and have the ability to develop and lead pharmacogenetic programs. they have a fundamental responsibility and accountability to advocate for the importance and rational for implementation of pharmacogenetic testing, to set recommendations to optimize medication therapy based on test results, to conduct and participate in research that accelerate the application of pharmacogenetics to clinical practice and to educate health care professionals and patients
The steady state concentrations of tamoxifen are achieved in about 4 weeks after initiation of therapy and the steady state concentrations for N-desmethyl tamoxifen are achieved in about 8 weeks
Summary
Tamoxifen is a hormone therapy belongs to the selective estrogen receptor modulators (SERMs) class of therapy. This drug class has both estrogenic and antiestrogenic effects. It acts as an estrogen (stimulating agent) in endometrium cell proliferation, cholesterol metabolism and bone density and acts as anti-estrogen (inhibiting agent) in the mammary tissue such as breast. Tamoxifen is a nonsteroidal drug that binds to estrogen receptors (ER) and lead to change or blockage in the estrogen dependent genes expression. The binding of tamoxifen to the nuclear chromatin for a long time results in reduction of DNA polymerase activity, impairment in thymidine utilization, blockage in ER-alpha or ER-beta receptors leading to both estrogenic and antiestrogenic effects [1,2]
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