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High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer

Inasu, Maria LU ; Bendahl, Pär Ola LU ; Fernö, Mårten LU ; Malmström, Per LU ; Borgquist, Signe LU and Kimbung, Siker LU (2021) In npj Breast Cancer 7(1).
Abstract

27-hydroxycholesterol (27HC), synthesized from cholesterol by the enzyme CYP27A1, differentially impacts estrogen receptor positive (ER+) breast cancer (BC) cell growth depending on estrogen levels. This study examined the association between CYP27A1 expression and prognosis in a cohort of 193 premenopausal patients with lymph node-negative primary BC with limited exposure to adjuvant systemic cancer treatments. In multivariable analyses among patients with ER+ tumors, high CYP27A1 protein and mRNA expressions were associated with four- and eight-fold reductions in the incidence of distant recurrence-free survival events: HRadj = 0.26, 95% CI = 0.07–0.93 and HRadj = 0.13, 95% CI = 0.03–0.60, respectively. In vitro... (More)

27-hydroxycholesterol (27HC), synthesized from cholesterol by the enzyme CYP27A1, differentially impacts estrogen receptor positive (ER+) breast cancer (BC) cell growth depending on estrogen levels. This study examined the association between CYP27A1 expression and prognosis in a cohort of 193 premenopausal patients with lymph node-negative primary BC with limited exposure to adjuvant systemic cancer treatments. In multivariable analyses among patients with ER+ tumors, high CYP27A1 protein and mRNA expressions were associated with four- and eight-fold reductions in the incidence of distant recurrence-free survival events: HRadj = 0.26, 95% CI = 0.07–0.93 and HRadj = 0.13, 95% CI = 0.03–0.60, respectively. In vitro studies revealed that 27HC treatment potently inhibited ER+ BC cell proliferation under lipid-depleted conditions regardless of estradiol levels, transcriptionally mediated through the downregulation of ER signaling with a concomitant upregulation of cholesterol export. Importantly, if validated, these results may have implications for adjuvant treatment decisions in premenopausal patients, especially when de-escalation of therapy is being considered.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
npj Breast Cancer
volume
7
issue
1
article number
127
publisher
Nature Publishing Group
external identifiers
  • scopus:85115604175
  • pmid:34556659
ISSN
2374-4677
DOI
10.1038/s41523-021-00333-6
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2021, The Author(s).
id
45e34efe-a1ef-44a0-9e99-ee86279d0e15
date added to LUP
2021-11-19 11:57:56
date last changed
2024-06-15 20:42:23
@article{45e34efe-a1ef-44a0-9e99-ee86279d0e15,
  abstract     = {{<p>27-hydroxycholesterol (27HC), synthesized from cholesterol by the enzyme CYP27A1, differentially impacts estrogen receptor positive (ER+) breast cancer (BC) cell growth depending on estrogen levels. This study examined the association between CYP27A1 expression and prognosis in a cohort of 193 premenopausal patients with lymph node-negative primary BC with limited exposure to adjuvant systemic cancer treatments. In multivariable analyses among patients with ER+ tumors, high CYP27A1 protein and mRNA expressions were associated with four- and eight-fold reductions in the incidence of distant recurrence-free survival events: HR<sub>adj</sub> = 0.26, 95% CI = 0.07–0.93 and HR<sub>adj</sub> = 0.13, 95% CI = 0.03–0.60, respectively. In vitro studies revealed that 27HC treatment potently inhibited ER+ BC cell proliferation under lipid-depleted conditions regardless of estradiol levels, transcriptionally mediated through the downregulation of ER signaling with a concomitant upregulation of cholesterol export. Importantly, if validated, these results may have implications for adjuvant treatment decisions in premenopausal patients, especially when de-escalation of therapy is being considered.</p>}},
  author       = {{Inasu, Maria and Bendahl, Pär Ola and Fernö, Mårten and Malmström, Per and Borgquist, Signe and Kimbung, Siker}},
  issn         = {{2374-4677}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{npj Breast Cancer}},
  title        = {{High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer}},
  url          = {{http://dx.doi.org/10.1038/s41523-021-00333-6}},
  doi          = {{10.1038/s41523-021-00333-6}},
  volume       = {{7}},
  year         = {{2021}},
}