Impact of 27-hydroxylase (CYP27A1) and 27-hydroxycholesterol in breast cancer
(2017) In Endocrine-Related Cancer 24(7). p.339-349- Abstract
The impact of systemic 27-hydroxycholesterol (27HC) and intratumoral CYP27A1 expression on pathobiology and clinical response to statins in breast cancer needs clarification. 27HC is an oxysterol produced from cholesterol by the monooxygenase CYP27A1, which regulates intracellular cholesterol homeostasis. 27HC also acts as an endogenous selective estrogen receptor (ER) modulator capable of increasing breast cancer growth and metastasis. 27HC levels can be modulated by statins or direct inhibition of CYP27A1, thereby attenuating its pro-tumorigenic activities. Herein, the effect of statins on serum 27HC and tumor-specific CYP27A1 expression was evaluated in 42 breast cancer patients treated with atorvastatin within a phase II clinical... (More)
The impact of systemic 27-hydroxycholesterol (27HC) and intratumoral CYP27A1 expression on pathobiology and clinical response to statins in breast cancer needs clarification. 27HC is an oxysterol produced from cholesterol by the monooxygenase CYP27A1, which regulates intracellular cholesterol homeostasis. 27HC also acts as an endogenous selective estrogen receptor (ER) modulator capable of increasing breast cancer growth and metastasis. 27HC levels can be modulated by statins or direct inhibition of CYP27A1, thereby attenuating its pro-tumorigenic activities. Herein, the effect of statins on serum 27HC and tumor-specific CYP27A1 expression was evaluated in 42 breast cancer patients treated with atorvastatin within a phase II clinical trial. Further, the associations between CYP27A1 expression with other primary tumor pathological features and clinical outcomes were studied in two additional independent cohorts. Statin treatment effectively decreased serum 27HC and deregulated CYP27A1 expression in tumors. However, these changes were not associated with anti-proliferative responses to statin treatment. CYP27A1 was heterogeneously expressed among primary tumors, with high expression significantly associated with high tumor grade, ER negativity and basal-like subtype. High CYP27A1 expression was independently prognostic for longer recurrence-free and overall survival. Importantly, the beneficial effect of high CYP27A1 in ER-positive breast cancer seemed limited to women aged ≤50 years. These results establish a link between CYP27A1 and breast cancer pathobiology and prognosis and propose that the efficacy of statins in reducing serum lipids does not directly translate to anti-proliferative effects in tumors. Changes in other undetermined serum or tumor factors suggestively mediate the anti-proliferative effects of statins in breast cancer.
(Less)
- author
- Kimbung, Siker LU ; Chang, Ching-Yi ; Bendahl, Pär-Ola LU ; Dubois, Laura ; Thompson, J Will ; McDonnell, Donald P and Borgquist, Signe LU
- organization
-
- Breastcancer-genetics
- Tumor microenvironment
- Breast cancer prevention & intervention (research group)
- Personalized Breast Cancer Treatment (research group)
- The Liquid Biopsy and Tumor Progression in Breast Cancer (research group)
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- publishing date
- 2017-07
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Endocrine-Related Cancer
- volume
- 24
- issue
- 7
- pages
- 11 pages
- publisher
- Society for Endocrinology
- external identifiers
-
- pmid:28442559
- wos:000404978400008
- scopus:85027280701
- ISSN
- 1479-6821
- DOI
- 10.1530/ERC-16-0533
- language
- English
- LU publication?
- yes
- id
- 71d7dd5a-cd43-40fa-b738-5a875562df7b
- date added to LUP
- 2017-11-07 16:03:55
- date last changed
- 2025-01-21 01:26:52
@article{71d7dd5a-cd43-40fa-b738-5a875562df7b, abstract = {{<p>The impact of systemic 27-hydroxycholesterol (27HC) and intratumoral CYP27A1 expression on pathobiology and clinical response to statins in breast cancer needs clarification. 27HC is an oxysterol produced from cholesterol by the monooxygenase CYP27A1, which regulates intracellular cholesterol homeostasis. 27HC also acts as an endogenous selective estrogen receptor (ER) modulator capable of increasing breast cancer growth and metastasis. 27HC levels can be modulated by statins or direct inhibition of CYP27A1, thereby attenuating its pro-tumorigenic activities. Herein, the effect of statins on serum 27HC and tumor-specific CYP27A1 expression was evaluated in 42 breast cancer patients treated with atorvastatin within a phase II clinical trial. Further, the associations between CYP27A1 expression with other primary tumor pathological features and clinical outcomes were studied in two additional independent cohorts. Statin treatment effectively decreased serum 27HC and deregulated CYP27A1 expression in tumors. However, these changes were not associated with anti-proliferative responses to statin treatment. CYP27A1 was heterogeneously expressed among primary tumors, with high expression significantly associated with high tumor grade, ER negativity and basal-like subtype. High CYP27A1 expression was independently prognostic for longer recurrence-free and overall survival. Importantly, the beneficial effect of high CYP27A1 in ER-positive breast cancer seemed limited to women aged ≤50 years. These results establish a link between CYP27A1 and breast cancer pathobiology and prognosis and propose that the efficacy of statins in reducing serum lipids does not directly translate to anti-proliferative effects in tumors. Changes in other undetermined serum or tumor factors suggestively mediate the anti-proliferative effects of statins in breast cancer.</p>}}, author = {{Kimbung, Siker and Chang, Ching-Yi and Bendahl, Pär-Ola and Dubois, Laura and Thompson, J Will and McDonnell, Donald P and Borgquist, Signe}}, issn = {{1479-6821}}, language = {{eng}}, number = {{7}}, pages = {{339--349}}, publisher = {{Society for Endocrinology}}, series = {{Endocrine-Related Cancer}}, title = {{Impact of 27-hydroxylase (CYP27A1) and 27-hydroxycholesterol in breast cancer}}, url = {{http://dx.doi.org/10.1530/ERC-16-0533}}, doi = {{10.1530/ERC-16-0533}}, volume = {{24}}, year = {{2017}}, }