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Breast Cancer Research
Published in: Breast Cancer Research 1/2020

01-12-2020 | Breast Cancer | Research article

CYP27A1 expression is associated with risk of late lethal estrogen receptor-positive breast cancer in postmenopausal patients

Authors: Siker Kimbung, Maria Inasu, Tor Stålhammar, Björn Nodin, Karin Elebro, Helga Tryggvadottir, Maria Ygland Rödström, Karin Jirström, Karolin Isaksson, Helena Jernström, Signe Borgquist

Published in: Breast Cancer Research | Issue 1/2020

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Abstract

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), HRadjusted = 1.93, 95%CI = 1.26–2.97, P = 0.003; breast cancer-specific survival (BCSS), HRadjusted = 2.33, 95%CI = 1.28–4.23, P = 0.006] and among patients ≥ 55 years presenting with ER+ tumors [OS, HRadjusted = 1.99, 95%CI = 1.24–3.21, P = 0.004; BCSS, HRadjusted = 2.78, 95%CI = 1.41–5.51, P = 0.003].
Among all patients in cohort 2 (median follow-up of 7.0 years), CYP27A1 expression was significantly associated with shorter OS and RFS in univariable analyses across the full follow-up period. However after adjusting for tumor characteristics and treatments, the association with survival after 5 years from diagnosis was non-significant among all patients [OS, HRadjusted = 1.08, 95%CI = 0.05–2.35, P = 0.83 and RFS, HRadjusted = 1.22, 95%CI = 0.68–2.18, P = 0.50] as well as among patients ≥ 55 years presenting with ER+ tumors [OS, HRadjusted = 0.46 95% CI = 0.11–1.98, P = 0.30 and RFS, HRadjusted = 0.97 95% CI = 0.44–2.10, P = 0.93].

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.
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Metadata
Title
CYP27A1 expression is associated with risk of late lethal estrogen receptor-positive breast cancer in postmenopausal patients
Authors
Siker Kimbung
Maria Inasu
Tor Stålhammar
Björn Nodin
Karin Elebro
Helga Tryggvadottir
Maria Ygland Rödström
Karin Jirström
Karolin Isaksson
Helena Jernström
Signe Borgquist
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2020
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-020-01347-x

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