dc.contributor.author
Mueller-Schoell, Anna
dc.contributor.author
Michelet, Robin
dc.contributor.author
Klopp-Schulze, Lena
dc.contributor.author
van Dyk, Madelé
dc.contributor.author
Mürdter, Thomas E.
dc.contributor.author
Schwab, Matthias
dc.contributor.author
Joerger, Markus
dc.contributor.author
Huisinga, Wilhelm
dc.contributor.author
Mikus, Gerd
dc.contributor.author
Kloft, Charlotte
dc.date.accessioned
2021-10-28T14:01:36Z
dc.date.available
2021-10-28T14:01:36Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/31478
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-31210
dc.description.abstract
Tamoxifen is used worldwide to treat estrogen receptor-positive breast cancer. It is extensively metabolized, and minimum steady-state concentrations of its metabolite endoxifen (CSS,min ENDX) >5.97 ng/mL have been associated with favorable outcome. Endoxifen formation is mediated by the enzyme CYP2D6, and impaired CYP2D6 function has been associated with lower CSS,min ENDX. In the Women’s Healthy Eating and Living (WHEL) study proposing the target concentration, 20% of patients showed subtarget CSS,min ENDX at tamoxifen standard dosing. CYP2D6 allele frequencies vary largely between populations, and as 87% of the patients in the WHEL study were White, little is known about the risk for subtarget CSS,min ENDX in other populations. Applying pharmacokinetic simulations, this study investigated the risk for subtarget CSS,min ENDX at tamoxifen standard dosing and the need for dose individualization in nine different biogeographical groups with distinct CYP2D6 allele frequencies. The high variability in CYP2D6 allele frequencies amongst the biogeographical groups resulted in an up to three-fold difference in the percentages of patients with subtarget CSS,min ENDX. Based on their CYP2D6 allele frequencies, East Asian breast cancer patients were identified as the population for which personalized, model-informed precision dosing would be most beneficial (28% of patients with subtarget CSS,min ENDX).
en
dc.format.extent
13 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
breast cancer
en
dc.subject
polymorphism
en
dc.subject
individualized dosing
en
dc.subject
personalized dosing
en
dc.subject
model-informed precision dosing
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::616 Krankheiten
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie, Therapeutik
dc.title
Computational Treatment Simulations to Assess the Need for Personalized Tamoxifen Dosing in Breast Cancer Patients of Different Biogeographical Groups
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
2432
dcterms.bibliographicCitation.doi
10.3390/cancers13102432
dcterms.bibliographicCitation.journaltitle
Cancers
dcterms.bibliographicCitation.number
10
dcterms.bibliographicCitation.originalpublishername
MDPI
dcterms.bibliographicCitation.volume
13
dcterms.bibliographicCitation.url
https://doi.org/10.3390/cancers13102432
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Pharmazie
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refubium.note.author
Die Publikation wurde aus Open Access Publikationsgeldern der Freien Universität Berlin gefördert.
de
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
2072-6694