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Endogenous estrogen receptor modulating oxysterols and breast cancer prognosis: Results from the MARIE patient cohort

BACKGROUND: 27-hydroxycholesterol (HC) and 25-HC were identified as endogenous selective estrogen receptor modulators (SERMs) and estrogen receptor (ER) modulators, respectively. They are hypothesized to play a role in multiple physiologic processes and pathologies, including breast cancer developme...

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Autores principales: Decker, Nina Sophia, Johnson, Theron, Behrens, Sabine, Obi, Nadia, Kaaks, Rudolf, Chang-Claude, Jenny, Fortner, Renée Turzanski
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403581/
https://www.ncbi.nlm.nih.gov/pubmed/37355720
http://dx.doi.org/10.1038/s41416-023-02315-w
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author Decker, Nina Sophia
Johnson, Theron
Behrens, Sabine
Obi, Nadia
Kaaks, Rudolf
Chang-Claude, Jenny
Fortner, Renée Turzanski
author_facet Decker, Nina Sophia
Johnson, Theron
Behrens, Sabine
Obi, Nadia
Kaaks, Rudolf
Chang-Claude, Jenny
Fortner, Renée Turzanski
author_sort Decker, Nina Sophia
collection PubMed
description BACKGROUND: 27-hydroxycholesterol (HC) and 25-HC were identified as endogenous selective estrogen receptor modulators (SERMs) and estrogen receptor (ER) modulators, respectively. They are hypothesized to play a role in multiple physiologic processes and pathologies, including breast cancer development and progression. METHODS: We evaluated circulating 27-HC and 25-HC, and outcomes following a breast cancer diagnosis in 2282 women from the MARIE study over median follow-up of 11.6 years. 27-HC and 25-HC were quantified by liquid chromatography–mass spectrometry. We calculated hazard ratios (HR) and 95% confidence intervals [CI] using multivariable Cox Proportional Hazards regression. RESULTS: We observed no associations between 27-HC and breast cancer prognosis overall. Associations between 27-HC and survival differed by circulating estradiol concentrations and endocrine therapy, but not by hormone receptor status. Among women with estradiol levels below the median (0.08 nM), 27-HC was associated with higher risk of all-cause mortality (HR(log2) = 1.80 [1.20–2.71]) and breast cancer-specific mortality (HR(log2) = 1.95 [1.14-3.31]). No associations were observed in women with estradiol levels above the median. Higher 25-HC levels were associated with lower risk of recurrence (HR(log2) = 0.87 [0.77-0.98]). CONCLUSION: Associations between 27-HC and breast cancer prognosis varied by circulating estradiol levels and endocrine therapy. Less consistent results were observed for 25-HC.
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spelling pubmed-104035812023-08-06 Endogenous estrogen receptor modulating oxysterols and breast cancer prognosis: Results from the MARIE patient cohort Decker, Nina Sophia Johnson, Theron Behrens, Sabine Obi, Nadia Kaaks, Rudolf Chang-Claude, Jenny Fortner, Renée Turzanski Br J Cancer Article BACKGROUND: 27-hydroxycholesterol (HC) and 25-HC were identified as endogenous selective estrogen receptor modulators (SERMs) and estrogen receptor (ER) modulators, respectively. They are hypothesized to play a role in multiple physiologic processes and pathologies, including breast cancer development and progression. METHODS: We evaluated circulating 27-HC and 25-HC, and outcomes following a breast cancer diagnosis in 2282 women from the MARIE study over median follow-up of 11.6 years. 27-HC and 25-HC were quantified by liquid chromatography–mass spectrometry. We calculated hazard ratios (HR) and 95% confidence intervals [CI] using multivariable Cox Proportional Hazards regression. RESULTS: We observed no associations between 27-HC and breast cancer prognosis overall. Associations between 27-HC and survival differed by circulating estradiol concentrations and endocrine therapy, but not by hormone receptor status. Among women with estradiol levels below the median (0.08 nM), 27-HC was associated with higher risk of all-cause mortality (HR(log2) = 1.80 [1.20–2.71]) and breast cancer-specific mortality (HR(log2) = 1.95 [1.14-3.31]). No associations were observed in women with estradiol levels above the median. Higher 25-HC levels were associated with lower risk of recurrence (HR(log2) = 0.87 [0.77-0.98]). CONCLUSION: Associations between 27-HC and breast cancer prognosis varied by circulating estradiol levels and endocrine therapy. Less consistent results were observed for 25-HC. Nature Publishing Group UK 2023-06-24 2023-08-24 /pmc/articles/PMC10403581/ /pubmed/37355720 http://dx.doi.org/10.1038/s41416-023-02315-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Decker, Nina Sophia
Johnson, Theron
Behrens, Sabine
Obi, Nadia
Kaaks, Rudolf
Chang-Claude, Jenny
Fortner, Renée Turzanski
Endogenous estrogen receptor modulating oxysterols and breast cancer prognosis: Results from the MARIE patient cohort
title Endogenous estrogen receptor modulating oxysterols and breast cancer prognosis: Results from the MARIE patient cohort
title_full Endogenous estrogen receptor modulating oxysterols and breast cancer prognosis: Results from the MARIE patient cohort
title_fullStr Endogenous estrogen receptor modulating oxysterols and breast cancer prognosis: Results from the MARIE patient cohort
title_full_unstemmed Endogenous estrogen receptor modulating oxysterols and breast cancer prognosis: Results from the MARIE patient cohort
title_short Endogenous estrogen receptor modulating oxysterols and breast cancer prognosis: Results from the MARIE patient cohort
title_sort endogenous estrogen receptor modulating oxysterols and breast cancer prognosis: results from the marie patient cohort
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403581/
https://www.ncbi.nlm.nih.gov/pubmed/37355720
http://dx.doi.org/10.1038/s41416-023-02315-w
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