Low Z-4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen.
4OHtam
concentration threshold
endoxifen
outcomes
therapeutic drug monitoring
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
01
11
2020
received:
05
10
2020
accepted:
27
11
2020
pubmed:
1
12
2020
medline:
15
1
2022
entrez:
30
11
2020
Statut:
ppublish
Résumé
Low steady-state levels of active tamoxifen metabolites have been associated with inferior treatment outcomes. In this retrospective analysis of 406 estrogen receptor-positive breast cancer (BC) patients receiving adjuvant tamoxifen as initial treatment, we have associated our previously reported thresholds for the two active metabolites, Z-endoxifen and Z-4-hydroxy-tamoxifen (Z-4OHtam), with treatment outcomes in an independent cohort of BC patients. Among all patients, metabolite levels did not affect survival. However, in the premenopausal subgroup receiving tamoxifen alone (n = 191) we confirmed an inferior BC -specific survival in patients with the previously described serum concentration threshold of Z-4OHtam ≤ 3.26 nm (HR = 2.37, 95% CI = 1.02-5.48, P = 0.039). The 'dose-response' survival trend in patients categorized to ordinal concentration cut-points of Z-4OHtamoxifen (≤ 3.26, 3.27-8.13, > 8.13 nm) was also replicated (P-trend log-rank = 0.048). Z-endoxifen was not associated with outcome. This is the first study to confirm the association between a published active tamoxifen metabolite threshold and BC outcome in an independent patient cohort. Premenopausal patients receiving 5-year of tamoxifen alone may benefit from therapeutic drug monitoring to ensure tamoxifen effectiveness.
Identifiants
pubmed: 33252186
doi: 10.1002/1878-0261.12865
pmc: PMC8024735
doi:
Substances chimiques
Antineoplastic Agents, Hormonal
0
Tamoxifen
094ZI81Y45
afimoxifene
17197F0KYM
4-hydroxy-N-desmethyltamoxifen
46AF8680RC
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
957-967Informations de copyright
© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
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