High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer
(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
- Inasu, Maria LU ; Bendahl, Pär Ola LU ; Fernö, Mårten LU ; Malmström, Per LU ; Borgquist, Signe LU and Kimbung, Siker LU
- organization
- publishing date
- 2021-12-01
- 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
-
- pmid:34556659
- scopus:85115604175
- 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
- 2024-06-29 21:44:42
@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}}, }