Dataset Information

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

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 (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.

SUBMITTER: Decker NS

PROVIDER: S-EPMC10403581 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Decker Nina Sophia NS Johnson Theron T Behrens Sabine S Obi Nadia N Kaaks Rudolf R Chang-Claude Jenny J Fortner Renée Turzanski RT

British journal of cancer 20230624 3

<h4>Background</h4>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.<h4>Methods</h4>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 ye ...[more]

PMID: 37355720

Similar Datasets

Project description:BackgroundBreast cancer is the most commonly diagnosed cancer in women worldwide, and underlying mechanistic pathways associated with breast cancer-specific and non-breast cancer-related deaths are of importance. Emerging evidence suggests a role of oxysterols, derivates of cholesterol, in multiple chronic diseases including breast cancer and coronary artery diseases. However, associations between oxysterols and survival have been minimally studied in women diagnosed with breast cancer. In this large breast cancer patient cohort, we evaluated associations between a panel of circulating oxysterols and mortality and recurrence outcomes.MethodsConcentrations of 13 circulating oxysterols representing different pathways of cholesterol metabolism were quantified using liquid-chromatography mass-spectrometry. Associations between baseline levels of oxysterols and cause-specific mortality outcomes and recurrence following a breast cancer diagnosis were assessed in 2282 women from the MARIE study over a median follow-up time of 11 years. We calculated hazard ratios (HR) and 95% confidence intervals (CI) using multivariable Cox proportional hazard models and competing risks models.ResultsWe observed no associations for circulating oxysterols and breast cancer-specific outcomes. Higher levels of six oxysterols were associated with an increased risk of cardiovascular disease death, including 24S-hydroxycholesterol (alternative bile acid pathway, HRlog2 = 1.73 (1.02, 2.93)), lanosterol (cholesterol biosynthesis pathway, HRlog2 = 1.95 (1.34, 2.83)), 7-ketocholesterol (HRlog2 = 1.26 (1.03, 1.55)), 5α,6α-epoxycholesterol (HRlog2 = 1.34 (1.02-1.77)), and 5a,6β-dihydroxycholestanol (HRlog2 = 1.34 (1.03, 1.76)). After adjusting for multiple comparisons, none of the associations were statistically significant.ConclusionWe provide first evidence on a range of circulating oxysterols and mortality following a breast cancer diagnosis, contributing to a better understanding of associations between different pathways of cholesterol metabolism and prognosis in women with a breast cancer diagnosis. The findings of this study suggest circulating oxysterols may be associated with cardiovascular mortality among women diagnosed with breast cancer. Further studies are needed to evaluate these oxysterols as potential markers of risk for cardiovascular mortality among women with a breast cancer diagnosis as well as their clinical potential.

Project description:The role of estrogen metabolism in determining breast cancer risk and differences in breast cancer rates between high-incidence and low-incidence nations is poorly understood. We measured urinary concentrations of estradiol and estrone (parent estrogens) and 13 estrogen metabolites formed by irreversible hydroxylation at the C-2, C-4, or C-16 positions of the steroid ring in a nested case-control study of 399 postmenopausal invasive breast cancer case participants and 399 matched control participants from the population-based Shanghai Women's Health Study cohort. Odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by quartiles of metabolic pathway groups, pathway ratios, and individual estrogens/estrogen metabolites were estimated by multivariable conditional logistic regression. Urinary estrogen/estrogen metabolite measures were compared with those of postmenopausal non-hormone-using Asian Americans, a population with three-fold higher breast cancer incidence rates. All statistical tests were two-sided. Urinary concentrations of parent estrogens were strongly associated with breast cancer risk (ORQ4vsQ1 = 1.94, 95% CI = 1.21 to 3.12, Ptrend = .01). Of the pathway ratios, the 2-pathway:total estrogens/estrogen metabolites and 2-pathway:parent estrogens were inversely associated with risk (ORQ4vsQ1 = 0.57, 95% CI = 0.35 to 0.91, Ptrend = .03, and ORQ4vsQ1 = 0.61, 95% CI = 0.37 to 0.99, Ptrend = .04, respectively). After adjusting for parent estrogens, these associations remained clearly inverse but lost statistical significance (ORQ4vsQ1 = 0.65, 95% CI = 0.39 to 1.06, Ptrend = .12 and ORQ4vsQ1 = 0.76, 95% CI = 0.44 to 1.32, Ptrend = .28). The urinary concentration of all estrogens/estrogen metabolites combined in Asian American women was triple that in Shanghai women. Lower urinary parent estrogen concentrations and more extensive 2-hydroxylation were each associated with reduced postmenopausal breast cancer risk in a low-risk nation. Markedly higher total estrogen/estrogen metabolite concentrations in postmenopausal United States women (Asian Americans) than in Shanghai women may partly explain higher breast cancer rates in the United States.

Project description:BackgroundMenstrual and parity history might impact the risk for breast cancer. Data on the impact of these factors on other tumor characteristics are limited.MethodsA single center retrospective cohort study comprising all women with estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative, early breast cancer whose tumors were sent to OncotypeDX analysis. The prespecified subgroups were investigated: age of menarche (< 12 vs. ≥ 12 years), number of deliveries (0 vs. ≥ 1 childbirth and ≥ 5 childbirth vs. other), age of first delivery (≥ 30 years vs. younger age) and postmenopausal compared to premenopausal. The impact of age of menopause was also assessed categorically, using early (< 45 years) and late age of menopause (> 55 years). Differences in tumor characteristics were evaluated using T-test or Mann Whitney for continuous variables or Fisher's exact test for categorical variables. Outcomes were assessed by Kaplan-Meier survival analysis, with the log-rank test.ResultsA total of 620 women were included. After median follow-up of 10.4 years, early menopause was associated with significantly worse disease-free survival (HR = 2.26, p = 0.004) and overall-survival (HR = 2.60, p = 0.004), and multiparity was associated with significant worse disease-free survival (HR = 2.16, p = 0.026). These differences remain significant in multivariate analyses. Post-menopausal women were more likely to have stronger ER intensity (p = 0.002) but progesterone receptor (PR) positivity was less frequent (p = 0.009(. Early age of menarche was associated with PR positivity (p = 0.039). No other associations were found between the evaluated subgroups and tumor characteristics.ConclusionsThe impact of endogenous estrogen exposure had little effect on breast cancer characteristics of early stage, luminal disease. Early menopause and multiparity were associated with worse outcome.

Project description:BackgroundThere are few studies on breast cancer outcomes in the Caribbean region. This study identified a retrospective cohort of female patients with nonmetastatic breast cancer in Haiti and conducted survival analyses to identify prognostic factors that may affect patient outcomes.MethodsThe cohort included 341 patients presenting between June 2012 and December 2016. The primary endpoint was event-free survival (EFS), defined as time to disease progression, recurrence, or death. Descriptive summaries of patient characteristics and treatments were reported. Survival curves were plotted using Kaplan-Meier estimation. Multivariate survival analyses were performed using Cox proportional hazards regression.ResultsMedian age at diagnosis was 49 years, with 64.2% being premenopausal. Most patients (55.1%) were staged as locally advanced. One hundred and sixty patients received neoadjuvant therapy: 33.3% of patients with early stage disease and 61.2% of those with locally advanced stage disease. Curative-intent surgery was performed in 278 (81.5%) patients, and 225 patients received adjuvant therapy. Adjuvant endocrine therapy was used in 82.0% of patients with estrogen receptor-positive disease. During the follow-up period, 28 patients died, 77 had disease recurrence, and 10 had progressive disease. EFS rates at 2 years and 3 years were 80.9% and 63.4%, respectively. After controlling for multiple confounders, the locally advanced stage group had a statistically significant adjusted hazard ratio for EFS of 3.27 compared with early stage.ConclusionPatients with nonmetastatic breast cancer in Haiti have more advanced disease, poorer prognostic factors, and worse outcomes compared with patients in high-income countries. Despite several limitations, curative treatment is possible in Haiti.Implications for practicePatients with breast cancer in Haiti have poor outcomes. Prior studies show that most Haitian patients are diagnosed at later stages. However, there are no rigorous studies describing how late-stage diagnosis and other prognostic factors affect outcomes in this population. This study presents a detailed analysis of survival outcomes and assessment of prognostic factors in patients with nonmetastatic breast cancer treated in Haiti. In addition to late-stage diagnosis, other unfavorable prognostic factors identified were young age and estrogen receptor-negative disease. The study also highlights that the availability of basic breast cancer treatment in Haiti can lead to promising early patient outcomes.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets