High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-09-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-021-00333-6 |
| _version_ | 1797421453352632320 |
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| author | Maria Inasu Pär-Ola Bendahl Mårten Fernö Per Malmström Signe Borgquist Siker Kimbung |
| author_facet | Maria Inasu Pär-Ola Bendahl Mårten Fernö Per Malmström Signe Borgquist Siker Kimbung |
| author_sort | Maria Inasu |
| collection | DOAJ |
| description | 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 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. |
| first_indexed | 2024-03-09T07:17:40Z |
| format | Article |
| id | doaj.art-42ce64d0f0ad4806b4fab2233af6540e |
| institution | Directory Open Access Journal |
| issn | 2374-4677 |
| language | English |
| last_indexed | 2024-03-09T07:17:40Z |
| publishDate | 2021-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj.art-42ce64d0f0ad4806b4fab2233af6540e2023-12-03T08:22:00ZengNature Portfolionpj Breast Cancer2374-46772021-09-017111110.1038/s41523-021-00333-6High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancerMaria Inasu0Pär-Ola Bendahl1Mårten Fernö2Per Malmström3Signe Borgquist4Siker Kimbung5Division of Oncology, Department of Clinical Sciences Lund, Lund UniversityDivision of Oncology, Department of Clinical Sciences Lund, Lund UniversityDivision of Oncology, Department of Clinical Sciences Lund, Lund UniversityDivision of Oncology, Department of Clinical Sciences Lund, Lund UniversityDivision of Oncology, Department of Clinical Sciences Lund, Lund UniversityDivision of Oncology, Department of Clinical Sciences Lund, Lund UniversityAbstract 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.https://doi.org/10.1038/s41523-021-00333-6 |
| spellingShingle | Maria Inasu Pär-Ola Bendahl Mårten Fernö Per Malmström Signe Borgquist Siker Kimbung High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer npj Breast Cancer |
| title | High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer |
| title_full | High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer |
| title_fullStr | High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer |
| title_full_unstemmed | High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer |
| title_short | High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer |
| title_sort | high cyp27a1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer |
| url | https://doi.org/10.1038/s41523-021-00333-6 |
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