Article ; Online: A Genome-Wide Association Study of Endoxifen Serum Concentrations and Adjuvant Tamoxifen Efficacy in Early-Stage Breast Cancer Patients.
Clinical pharmacology and therapeutics
2024
Abstract: Tamoxifen is part of the standard of care of endocrine therapy for adjuvant treatment of breast cancer. However, survival outcomes with tamoxifen are highly variable. The concentration of endoxifen, the 30-100 times more potent metabolite of tamoxifen ... ...
| Abstract | Tamoxifen is part of the standard of care of endocrine therapy for adjuvant treatment of breast cancer. However, survival outcomes with tamoxifen are highly variable. The concentration of endoxifen, the 30-100 times more potent metabolite of tamoxifen and bioactivated by the CYP2D6 enzyme, has been described as the most relevant metabolite of tamoxifen metabolism. A genome-wide association study (GWAS) was performed with the objective to identify genetic polymorphisms associated with endoxifen serum concentration levels and clinical outcome in early-stage breast cancer patients receiving tamoxifen. A GWAS was conducted in 608 women of the CYPTAM study (NTR1509/PMID: 30120701). Germline DNA and clinical and survival characteristics were readily available. Genotyping was performed on Infinium Global Screening Array (686,082 markers) and single nucleotide polymorphism (SNP) imputation by using 1000 Genomes. Relapse-free survival during tamoxifen (RFSt) was defined the primary clinical outcome. Endoxifen serum concentration was analyzed as a continuous variable. Several genetic variants reached genome-wide significance (P value: ≤5 × 10 |
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| Language | English |
| Publishing date | 2024-03-19 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 123793-7 |
| ISSN | 1532-6535 ; 0009-9236 |
| ISSN (online) | 1532-6535 |
| ISSN | 0009-9236 |
| DOI | 10.1002/cpt.3255 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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