Study of Tamoxifen Dose Escalation in Breast Cancer Patients With CYP2D6 Polymorphisms
Status:
Completed
Trial end date:
2012-12-01
Target enrollment:
Participant gender:
Summary
Tamoxifen is an important drug for the treatment of breast cancer. Used adjuvantly after
operation in early breast cancer, tamoxifen reduces annual recurrence rate by half and cancer
death by one third. Used preventatively it also reduces the risk of breast cancer by 50% in
women at high risk for developing the disease Tamoxifen needs to be activated in the body to
an active form called endoxifen, mainly by the enzyme called CYP2D6. Patients have variable
capability to activate tamoxifen due to variable function of this enzyme. Studies showed
clear correlation of specific genetic variant of CYP2D6 with endoxifen blood levels. It is
estimated that up to 25% Caucasian population have reduced or even absent CYP2D6 function.
More recently, there were studies that showed the correlation with genetic variant of CYP2D6
and breast cancer relapse in early breast cancer patients treated with tamoxifen. Food and
Drug Authority (FDA) in America and recommended checking CYP2D6 genotype in patients
receiving tamoxifen treatment, but they did not specify how to interpret the genotype results
and what kind actions to take in patient with adverse genotype. The aim of the investigators
study is to see if increasing tamoxifen in patients with genetic polymorphism of CYP2D6 will
increase endoxifen level to the same range of most patients who have wild type (normal
functional)CYP2D6.