Endogenous estrogen receptor modulating oxysterols and breast cancer prognosis
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Abstract
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 (HRlog2 = 1.80 [1.20-2.71]) and breast cancer-specific mortality (HRlog2 = 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 (HRlog2 = 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.
Bibliographical data
Original language | English |
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ISSN | 0007-0920 |
DOIs | |
Publication status | Published - 08.2023 |
Comment Deanary
© 2023. The Author(s).
PubMed | 37355720 |
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