A meta-analysis of the association between CYP2D6 genotype and resistance to tamoxifen treatment in breast cancer patients Open Access

Mody, Malay (Spring 2021)

Permanent URL: https://etd.library.emory.edu/concern/etds/p5547s797?locale=en


Objective: To obtain summary measures of association between CYP2D6 genotype and breast cancer mortality or recurrence after tamoxifen treatment from published studies each using unique cohorts. Results will be used to investigate potential sources of heterogeneity in CYP2D6-tamoxifen studies, including the variants genotyped in a study, the DNA source, ethnic descent of the study cohort, study participants’ menopausal status, or the estrogen receptor-status of their tumor.

Methods: This meta-analysis will include only original research and stratify groups based on their study characteristics. Analyses will be performed using Ahern et al.’s web tool on the Shiny platform, which runs the ‘metafor’ R package and provides measures of association and 95% confidence intervals. These values will then be compared in to evaluate which categories account for substantial heterogeneity. Results: Of CYP2D6 variants genotyped, DNA source, ethnic descent of study cohort, menopausal status, and estrogen receptor status, only ethnic descent accounted for substantial heterogeneity. Studies using cohorts of patients of Asian descent resulted in RR (95% CI) = 2.39 (1.82,3.15), while those using cohorts of European patients resulted in RR (95% CI) = 1.25 (1.09, 1.43).

Conclusions: This meta-analysis demonstrates a heterogeneity in relative risks reported by manuscripts using Asian cohorts when compared to European cohorts. Future research may include further research on immortal person-time bias in CYP2D6- tamoxifen studies, research on the role of genes other than CYP2D6 in tamoxifen treatment outcomes, and clinical trials to investigate outcomes after using CYP2D6 genotyping to inform treatment decisions.

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