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Low Z‐4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen
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 th...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024735/ https://www.ncbi.nlm.nih.gov/pubmed/33252186 http://dx.doi.org/10.1002/1878-0261.12865 |
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author | Helland, Thomas Naume, Bjørn Hustad, Steinar Bifulco, Ersilia Kvaløy, Jan Terje Sætersdal, Anna Barbro Synnestvedt, Marit Lende, Tone Hoel Gilje, Bjørnar Mjaaland, Ingvil Weyde, Kjetil Blix, Egil Støre Wiedswang, Gro Borgen, Elin Hertz, Daniel Louis Janssen, Emiel Adrianus Maria Mellgren, Gunnar Søiland, Håvard |
author_facet | Helland, Thomas Naume, Bjørn Hustad, Steinar Bifulco, Ersilia Kvaløy, Jan Terje Sætersdal, Anna Barbro Synnestvedt, Marit Lende, Tone Hoel Gilje, Bjørnar Mjaaland, Ingvil Weyde, Kjetil Blix, Egil Støre Wiedswang, Gro Borgen, Elin Hertz, Daniel Louis Janssen, Emiel Adrianus Maria Mellgren, Gunnar Søiland, Håvard |
author_sort | Helland, Thomas |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8024735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80247352021-04-13 Low Z‐4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen Helland, Thomas Naume, Bjørn Hustad, Steinar Bifulco, Ersilia Kvaløy, Jan Terje Sætersdal, Anna Barbro Synnestvedt, Marit Lende, Tone Hoel Gilje, Bjørnar Mjaaland, Ingvil Weyde, Kjetil Blix, Egil Støre Wiedswang, Gro Borgen, Elin Hertz, Daniel Louis Janssen, Emiel Adrianus Maria Mellgren, Gunnar Søiland, Håvard Mol Oncol Research Articles 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. John Wiley and Sons Inc. 2020-12-14 2021-04 /pmc/articles/PMC8024735/ /pubmed/33252186 http://dx.doi.org/10.1002/1878-0261.12865 Text en © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Helland, Thomas Naume, Bjørn Hustad, Steinar Bifulco, Ersilia Kvaløy, Jan Terje Sætersdal, Anna Barbro Synnestvedt, Marit Lende, Tone Hoel Gilje, Bjørnar Mjaaland, Ingvil Weyde, Kjetil Blix, Egil Støre Wiedswang, Gro Borgen, Elin Hertz, Daniel Louis Janssen, Emiel Adrianus Maria Mellgren, Gunnar Søiland, Håvard Low Z‐4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen |
title | Low Z‐4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen |
title_full | Low Z‐4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen |
title_fullStr | Low Z‐4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen |
title_full_unstemmed | Low Z‐4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen |
title_short | Low Z‐4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen |
title_sort | low z‐4ohtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024735/ https://www.ncbi.nlm.nih.gov/pubmed/33252186 http://dx.doi.org/10.1002/1878-0261.12865 |
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