CYP27A1 expression is associated with risk of late lethal estrogen receptor-positive breast cancer in postmenopausal patients.
Aged
Antineoplastic Agents, Hormonal
/ therapeutic use
Biomarkers, Tumor
/ analysis
Breast
/ pathology
Breast Neoplasms
/ diagnosis
Chemotherapy, Adjuvant
Cholestanetriol 26-Monooxygenase
/ analysis
Disease-Free Survival
Female
Follow-Up Studies
Humans
Hydroxycholesterols
/ metabolism
Immunohistochemistry
Kaplan-Meier Estimate
Mastectomy
Middle Aged
Neoplasm Grading
Neoplasm Recurrence, Local
/ epidemiology
Postmenopause
Prognosis
Receptors, Estrogen
/ analysis
Time Factors
27-hydroxycholesterol
Breast cancer
CYP27A1
Cholesterol
Prognosis
Journal
Breast cancer research : BCR
ISSN: 1465-542X
Titre abrégé: Breast Cancer Res
Pays: England
ID NLM: 100927353
Informations de publication
Date de publication:
11 11 2020
11 11 2020
Historique:
received:
24
03
2020
accepted:
01
10
2020
entrez:
12
11
2020
pubmed:
13
11
2020
medline:
22
6
2021
Statut:
epublish
Résumé
27-Hydroxycholesterol (27HC) stimulates estrogen receptor-positive (ER+) breast cancer (BC) progression. Inhibiting the sterol 27-hydroxylase (CYP27A1) abrogates these growth-promoting effects of 27HC in mice. However, the significance of CYP27A1 expression on BC biology and prognosis is unclear. Intratumoral CYP27A1 expression in invasive BC was measured by immunohistochemistry in two Swedish population-based cohorts (n = 645 and n = 813, respectively). Cox proportional hazards models were used to evaluate the association between CYP27A1 expression and prognosis. CYP27A1 was highly expressed in less than 1/3 of the tumors. High CYP27A1 expression was more frequent among high-grade tumors lacking hormone receptor expression and with larger tumor sizes. Over a median of 12.2 years follow-up in cohort 1, high CYP27A1 expression was associated with impaired survival, specifically after 5 years from diagnosis among all patients [overall survival (OS), HR CYP27A1 demonstrated great potentials as a biomarker of aggressive tumor biology and late lethal disease in postmenopausal patients with ER+ BC. Future studies should investigate if the benefits of prolonged endocrine therapy and cholesterol-lowering medication in BC are modified by CYP27A1 expression.
Sections du résumé
BACKGROUND
27-Hydroxycholesterol (27HC) stimulates estrogen receptor-positive (ER+) breast cancer (BC) progression. Inhibiting the sterol 27-hydroxylase (CYP27A1) abrogates these growth-promoting effects of 27HC in mice. However, the significance of CYP27A1 expression on BC biology and prognosis is unclear.
METHODS
Intratumoral CYP27A1 expression in invasive BC was measured by immunohistochemistry in two Swedish population-based cohorts (n = 645 and n = 813, respectively). Cox proportional hazards models were used to evaluate the association between CYP27A1 expression and prognosis.
RESULTS
CYP27A1 was highly expressed in less than 1/3 of the tumors. High CYP27A1 expression was more frequent among high-grade tumors lacking hormone receptor expression and with larger tumor sizes. Over a median of 12.2 years follow-up in cohort 1, high CYP27A1 expression was associated with impaired survival, specifically after 5 years from diagnosis among all patients [overall survival (OS), HR
CONCLUSION
CYP27A1 demonstrated great potentials as a biomarker of aggressive tumor biology and late lethal disease in postmenopausal patients with ER+ BC. Future studies should investigate if the benefits of prolonged endocrine therapy and cholesterol-lowering medication in BC are modified by CYP27A1 expression.
Identifiants
pubmed: 33176848
doi: 10.1186/s13058-020-01347-x
pii: 10.1186/s13058-020-01347-x
pmc: PMC7656740
doi:
Substances chimiques
Antineoplastic Agents, Hormonal
0
Biomarkers, Tumor
0
Hydroxycholesterols
0
Receptors, Estrogen
0
27-hydroxycholesterol
6T2NA6P5SQ
CYP27A1 protein, human
EC 1.14.15.15
Cholestanetriol 26-Monooxygenase
EC 1.14.15.15
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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