Tamoxifen DNA Typing System

Tamoxifen Management

Tamoxifen (Nolvadex®) is widely prescribed for adjunctive therapy of estrogen receptor positive (ER+) breast carcinoma. Large clinical trials over many years have demonstrated the efficacy and safety of the drug in the prevention and delay of recurrent breast carcinoma.

Tamoxifen is a pro-drug. It functions as an Estrogen Receptor Inhibitor requiring activation and conversion of the drug to the functional metabolites, 4- OH-Tamoxifen and endoxifen for clinical effect. Endoxifen is the most potent Tamoxifen (x100) metabolite. Cytochrome P450-2D6 is required for endoxifen synthesis.

Common DNA polymorphisms in Cytochrome P450-2D6 can reduce enzyme activity and as a result decrease endoxifen therapeutic concentrations. These changes result in an increase in the frequency of disease recurrence and a decrease in five year survival rate.

The Tamoxifen DNA Typing System analyzes 20 gene variants found within the highly polymorphic CYP 2D6 gene which result in decreased CYP2D6 functional activity. Patients testing positive should be considered for alternative estrogen receptor (SERM) or aromatase inhibitor therapy.

Presentation:
DNA-Guided Tamoxifen Therapy for Breast Cancer

References:
Scientific and Clinical Evidence Related to CYP2D6 Polymorphism and Response to Tamoxifen Therapy Food and Drug Administration, Center for Drug Evaluation and Research, Pharmaceutical Science (ACPS) October 18, 2006



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