Low Z-4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen.

Autor: Helland T; Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.; Department of Clinical Science, University of Bergen, Norway., Naume B; Department of Oncology, Division of Cancer Medicine, Oslo University Hospital, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway., Hustad S; Core Facility for Metabolomics, Department of Clinical Science, University of Bergen, Norway., Bifulco E; Core Facility for Metabolomics, Department of Clinical Science, University of Bergen, Norway., Kvaløy JT; Department of Mathematics and Physics, University of Stavanger, Norway.; Department of Research, Stavanger University Hospital, Norway., Saetersdal AB; Department of Oncology, Division of Cancer Medicine, Oslo University Hospital, Norway., Synnestvedt M; Department of Oncology, Division of Cancer Medicine, Oslo University Hospital, Norway., Lende TH; Department of Surgery, Section for Breast and Endocrine Surgery, Stavanger University Hospital, Norway., Gilje B; Department of Oncology and Radiotherapy, Stavanger University Hospital, Norway., Mjaaland I; Department of Oncology and Radiotherapy, Stavanger University Hospital, Norway., Weyde K; Department of Oncology, Sykehuset Innlandet, Gjøvik, Norway., Blix ES; Immunology Research Group, Institute of Medical Biology, University of Tromsø, Norway.; Department of Oncology, University Hospital of North Norway, Tromsø, Norway., Wiedswang G; Department of GI-Surgery, Oslo University Hospital, Norway., Borgen E; Department of Pathology, Oslo University Hospital, Norway., Hertz DL; Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA., Janssen EAM; Department of Pathology, Stavanger University Hospital, Norway.; Department of Bioscience and Environmental Engineering, University of Stavanger, Norway., Mellgren G; Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.; Department of Clinical Science, University of Bergen, Norway., Søiland H; Department of Clinical Science, University of Bergen, Norway.; Department of Oncology and Radiotherapy, Stavanger University Hospital, Norway.
Jazyk: angličtina
Zdroj: Molecular oncology [Mol Oncol] 2021 Apr; Vol. 15 (4), pp. 957-967. Date of Electronic Publication: 2020 Dec 14.
DOI: 10.1002/1878-0261.12865
Abstrakt: 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.
(© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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