Does Next Generation Sequencing (NGS)-Based CYP2D6 Sequencing Improve Genotype-Phenotype Concordance in Tamoxifen-Treated Patients?

NGS sequencing of *CYP2D6* improves genotype-phenotype concordance compared to targeted genotyping by detecting rare variants and structural variants

A retrospective study of 68 tamoxifen-treated patients compares targeted CYP2D6 genotyping (TaqMan/Luminex) with full NGS sequencing. NGS changes phenotype classification in 19% of cases, primarily by detecting rare variants, duplications, and hybrid genes missed by targeted approaches. These reclassifications have a demonstrated pharmacokinetic impact on tamoxifen exposure (measured by endoxifen).

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A 19% phenotypic reclassification rate with NGS vs targeted genotyping is clinically significant for CYP2D6. In the tamoxifen context — where metabolizer phenotype determines conversion to active endoxifen and potentially therapeutic efficacy — this result argues for NGS adoption in oncology PGx programs.