Evidence map›Paper›PMID 42380819›Full record

ArticleBMC cancer2026

Comprehensive CYP2D6 genotyping improves phenotype classification and highlights methodological pitfalls in tamoxifen-treated breast cancer.

Linda Alkebbeh, Anne Berndt, Christian Oberkanins, Mazen Kenj, Gernot Kriegshäuser, Lama A Youssef

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Article in BMC cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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6 authors.

Linda AlkebbehDepartment of Pharmaceutics and Pharmaceutical Technology, Program of Clinical and Hospital Pharmacy, Faculty of Pharmacy, Damascus University, Damascus, Syrian Arab Republic.
Anne BerndtViennaLab Diagnostics, Vienna, Austria.
Christian OberkaninsViennaLab Diagnostics, Vienna, Austria.
Mazen KenjKenj Medical Cytogenetic Laboratories, Damascus, Syrian Arab Republic.
Gernot KriegshäuserDepartment of Medical Genetics, Yerevan State Medical University, Yerevan, Armenia.
Lama A YoussefDepartment of Pharmaceutics and Pharmaceutical Technology, Program of Clinical and Hospital Pharmacy, Faculty of Pharmacy, Damascus University, Damascus, Syrian Arab Republic. lama.youssef@damascusuniversity.edu.sy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe clinical utility of CYP2D6 genotyping in predicting tamoxifen outcomes remains controversial, partly due to incomplete allele coverage and limited assessment of copy number variation (CNV). We aimed to expand CYP2D6 genetic profiling in Syrian breast cancer patients and to reassess phenotype classification and its clinical relevance.

methodsIn this retrospective cohort of estrogen receptor-positive breast cancer patients treated with adjuvant tamoxifen, CYP2D6 genotyping was performed using a test strip-based assay complemented by semi-quantitative PCR for CNV detection. Selected results were validated by next-generation sequencing (NGS). Diplotypes were translated into activity scores to assign metabolizer phenotypes. Disease-free survival (DFS) was evaluated using time-to-event analyses.

resultsExpanded CYP2D6 profiling, incorporating broader allele coverage and CNV analysis, led to metabolizer phenotype reclassification in 19% of patients. NGS identified primer-binding region variants responsible for allele drop-out in conventional assays. No significant association between CYP2D6 phenotype and DFS was observed in the overall cohort. However, exploratory stage-specific analyses suggested shorter DFS among patients with reduced CYP2D6 activity in Stage II disease (HR = 3.59; 95% CI 2.34-67.48), although estimates were imprecise due to small subgroup size.

conclusionsComprehensive CYP2D6 profiling improves phenotype assignment and highlights methodological pitfalls that may contribute to inconsistencies in pharmacogenetic studies. While no definitive association with clinical outcomes was observed in the overall cohort, these findings underscore the importance of analytically robust genotyping strategies and warrant validation in larger, prospectively designed cohorts, and highlight the importance of comprehensive genotyping strategies in resolving inconsistencies across pharmacogenetic studies.

Indexed as

Antineoplastic Agents, HormonalBreast NeoplasmsCytochrome P-450 CYP2D6TamoxifenAdultAgedDisease-Free SurvivalDNA Copy Number VariationsFemaleGenotypeHigh-Throughput Nucleotide SequencingHumansMiddle AgedPhenotypeRetrospective StudiesAntineoplastic Agents, HormonalCytochrome P-450 CYP2D6TamoxifenBreast cancerCopy number variationCYP2D6PharmacogeneticsPhenotype reclassificationTamoxifen

Identifiers

PMID42380819
PMCPMC13587297

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