Background: Tamoxifen (TAM) is a frequently used hormonal prodrug for patients with
breast cancer that needs to be activated by cytochrome P450 2D6 (CYP2D6) into Zusammen-endoxifen
Objective: The purpose of the study was to determine the association between CYP2D6*10
(c.100C>T) genotype and attainment of the plasma steady-state Z-END minimal threshold concentration
(MTC) in Indonesian women with breast cancer.
Methods: A cross-sectional study was performed in 125 ambulatory patients with breast cancer
consuming TAM at 20 mg/day for at least 4 months. The frequency distribution of CYP2D6*10
(c.100C>T) genotypes (C/C: wild type; C/T: heterozygous mutant; T/T: homozygous mutant) was
detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP),
the results of which were subsequently confirmed by sequencing. The genotypes were categorized
into plasma Z- END concentrations of <5.9 ng/mL and ≥5.9 ng/mL, which were measured using
ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).
Results: Percentages of C/C, CT, and T/T genotypes were 22.4%, 29.6%, and 48.8%, respectively.
Median (25-75%) Z-END concentrations in C/C, C/T, and T/T genotypes were 9.58 (0.7-6.0), 9.86
(0.7-26.6), and 3.76 (0.9-26.6) ng/mL, respectively. Statistical analysis showed a significant difference
in median Z-END concentration between patients with T/T genotype and those with C/C or C/T
genotypes (p<0.001). There was a significant association between CYP2D6*10 (c.100C>T) genotypes
and attainment of plasma steady-state Z-END MTC (p<0.001).
Conclusion: There was a significant association between CYP2D6*10 (c.100C>T) and attainment of
plasma steady-state Z-END MTC in Indonesian breast cancer patients receiving TAM at a dose of 20