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Association of CYP2D6*10 (c. 100 C>T) Genotype with Z-END Concentration in Patients with Breast Cancer Receiving Tamoxifen Therapy in Indonesian Population

[ Vol. 19 , Issue. 8 ]

Author(s):

Yenny*, Sonar S. Panigoro, Denni J. Purwanto, Adi Hidayat, Melva Louisa, Rizka Andalusia and Rianto Setiabudy   Pages 1198 - 1206 ( 9 )

Abstract:


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 (Z-END).

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 mg/day.

Keywords:

CYP2D6*10 (c.100C>T), breast cancer, tamoxifen, Z-endoxifen, steady state concentration, Indonesian population.

Affiliation:

Doctoral Program, Faculty of Medicine, Universitas Indonesia, Jakarta, Department of Surgery, Surgical Oncology Division, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Surgical Oncology Department, Dharmais National Cancer Center Hospital, Jakarta, Department of Community Medicine, Faculty of Medicine, Trisakti University, Jakarta, Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Department of Research and Development, Dharmais National Cancer Center Hospital, Jakarta, Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta

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