CYP2D6 Genotyping for Optimization of Tamoxifen Therapy in Indonesian Women with ER+ Breast Cancer.

Abstract

Background: Certain CYP2D6 genotypes are linked to a lower efficacy of tamoxifen therapy. This study aimed to observe CYP2D6 polymorphisms and examine the impact of CYP2D6 genotyping among tamoxifen-treated breast cancer patients in Indonesia. Methods: 150 breast cancer participants were recruited. Buccal swab samples were collected; gDNA was extracted and genotyped using the qPCR method. Blood samples were collected, and measurement of tamoxifen metabolite levels was performed using UPLC-MS/MS. Results: 43.3% (n = 65) of participants were IMs. *10 was the most common haplotype (n = 89, 29.7%), followed by *36 (n = 73, 29.7%), making *10/*36 the most common diplotype (n = 34, 22.7%) in this study. The difference in endoxifen levels between the NM and IM-PM groups at baseline was statistically significant (p ≤ 0.001). A dose increase in tamoxifen to 40 mg daily successfully increased endoxifen levels in IMs to a similar level with NMs at baseline (p > 0.05) without exposing IMs to serious side effects. No statistically significant differences were observed between the 20mg group and the 40 mg group on the adjusted OS (p > 0.05) and the adjusted PFS (p > 0.05). Conclusions: Our study observed a considerably high proportion of CYP2D6 IMs. The dose adjustment of tamoxifen was proven to significantly and safely improve the level of endoxifen and survival.