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\begin{document}

\title{Pharmacogenetics and Pharmacokinetics of Tamoxifen in a Zimbabwean
breast cancer cohort}



\author[1]{Bianza  Mbavha }%
\author[1]{Roslyn Thelingwani}%
\author[1]{Zedias  Chikwambi}%
\author[2]{Anna  Nyakabau}%
\author[1]{Collen Masimirembwa}%
\affil[1]{African Institute of Bio-medical Science and Technology}%
\affil[2]{University of Zimbabwe Faculty of Medicine}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\begin{abstract}
Tamoxifen is the most used hormonal therapy for estrogen receptor
positive breast cancer. CYP2D6 is the main enzyme in the metabolic
pathway of tamoxifen to endoxifen. Variations in endoxifen plasma
concentrations are associated with CYP2D6 polymorphisms. This study
aimed to determine the association between the CYP2D6 polymorphisms and
endoxifen plasma concentrations in a cohort of Zimbabwean breast cancer
patients (n = 40). TaqMan genotyping and copy number assays were done to
determine CYP2D6 genotypes. Tamoxifen and metabolites were quantitated
using LC-MS/MS. The population had high frequencies of the CYP2D6
reduced function alleles, *17 (15\%) and *29 (18\%). The median
endoxifen concentration was 4.78 ng/ml and 55\% of the patients, mostly
intermediate metabolizers were below the endoxifen therapeutic threshold
5.97 ng/ml. The CYP2D6 phenotypes and activity scores were significantly
associated with endoxifen plasma concentrations (p = 0.0151) and with
endoxifen to N-desmethyl tamoxifen ratios (p = 0.0006).%
\end{abstract}%



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\textbf{Hosted file}

\verb`Tamoxifen_manuscript_BJCP.docx`  available at \url{https://authorea.com/users/603981/articles/634106-pharmacogenetics-and-pharmacokinetics-of-tamoxifen-in-a-zimbabwean-breast-cancer-cohort}

\textbf{Hosted file}

\verb`Tamoxifen_Figure 1_BJCP.docx`  available at \url{https://authorea.com/users/603981/articles/634106-pharmacogenetics-and-pharmacokinetics-of-tamoxifen-in-a-zimbabwean-breast-cancer-cohort}

\textbf{Hosted file}

\verb`Tamoxifen_Figure 2_BJCP.docx`  available at \url{https://authorea.com/users/603981/articles/634106-pharmacogenetics-and-pharmacokinetics-of-tamoxifen-in-a-zimbabwean-breast-cancer-cohort}

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