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Targeting HMG-CoA reductase with statins in a window-of-opportunity breast cancer trial.

Bjarnadottir, Olöf LU ; Romero, Quinci LU ; Bendahl, Pär-Ola LU ; Jirström, Karin LU orcid ; Rydén, Lisa LU orcid ; Loman, Niklas LU ; Uhlén, Mathias ; Johannesson, Henrik ; Rose, Carsten LU and Grabau, Dorthe LU , et al. (2013) In Breast Cancer Research and Treatment 138(2). p.499-508
Abstract
Lipophilic statins purportedly exert anti-tumoral effects on breast cancer by decreasing proliferation and increasing apoptosis. HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate pathway, is the target of statins. However, data on statin-induced effects on HMGCR activity in cancer are limited. Thus, this pre-operative study investigated statin-induced effects on tumor proliferation and HMGCR expression while analyzing HMGCR as a predictive marker for statin response in breast cancer treatment. The study was designed as a window-of-opportunity trial and included 50 patients with primary invasive breast cancer. High-dose atorvastatin (i.e., 80 mg/day) was prescribed to patients for 2 weeks before surgery. Pre- and... (More)
Lipophilic statins purportedly exert anti-tumoral effects on breast cancer by decreasing proliferation and increasing apoptosis. HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate pathway, is the target of statins. However, data on statin-induced effects on HMGCR activity in cancer are limited. Thus, this pre-operative study investigated statin-induced effects on tumor proliferation and HMGCR expression while analyzing HMGCR as a predictive marker for statin response in breast cancer treatment. The study was designed as a window-of-opportunity trial and included 50 patients with primary invasive breast cancer. High-dose atorvastatin (i.e., 80 mg/day) was prescribed to patients for 2 weeks before surgery. Pre- and post-statin paired tumor samples were analyzed for Ki67 and HMGCR immunohistochemical expression. Changes in the Ki67 expression and HMGCR activity following statin treatment were the primary and secondary endpoints, respectively. Up-regulation of HMGCR following atorvastatin treatment was observed in 68 % of the paired samples with evaluable HMGCR expression (P = 0.0005). The average relative decrease in Ki67 expression following atorvastatin treatment was 7.6 % (P = 0.39) in all paired samples, whereas the corresponding decrease in Ki67 expression in tumors expressing HMGCR in the pre-treatment sample was 24 % (P = 0.02). Furthermore, post-treatment Ki67 expression was inversely correlated to post-treatment HMGCR expression (rs = -0.42; P = 0.03). Findings from this study suggest that HMGCR is targeted by statins in breast cancer cells in vivo, and that statins may have an anti-proliferative effect in HMGCR-positive tumors. Future studies are needed to evaluate HMGCR as a predictive marker for the selection of breast cancer patients who may benefit from statin treatment. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Breast Cancer Research and Treatment
volume
138
issue
2
pages
499 - 508
publisher
Springer
external identifiers
  • wos:000316821300015
  • pmid:23471651
  • scopus:84879411965
  • pmid:23471651
ISSN
1573-7217
DOI
10.1007/s10549-013-2473-6
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000), Oncology, MV (013035000), Surgery (Lund) (013009000)
id
ee10e5c2-43af-428f-acc8-3c45054b1851 (old id 3628420)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23471651?dopt=Abstract
date added to LUP
2016-04-01 10:34:49
date last changed
2024-01-06 20:07:48
@article{ee10e5c2-43af-428f-acc8-3c45054b1851,
  abstract     = {{Lipophilic statins purportedly exert anti-tumoral effects on breast cancer by decreasing proliferation and increasing apoptosis. HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate pathway, is the target of statins. However, data on statin-induced effects on HMGCR activity in cancer are limited. Thus, this pre-operative study investigated statin-induced effects on tumor proliferation and HMGCR expression while analyzing HMGCR as a predictive marker for statin response in breast cancer treatment. The study was designed as a window-of-opportunity trial and included 50 patients with primary invasive breast cancer. High-dose atorvastatin (i.e., 80 mg/day) was prescribed to patients for 2 weeks before surgery. Pre- and post-statin paired tumor samples were analyzed for Ki67 and HMGCR immunohistochemical expression. Changes in the Ki67 expression and HMGCR activity following statin treatment were the primary and secondary endpoints, respectively. Up-regulation of HMGCR following atorvastatin treatment was observed in 68 % of the paired samples with evaluable HMGCR expression (P = 0.0005). The average relative decrease in Ki67 expression following atorvastatin treatment was 7.6 % (P = 0.39) in all paired samples, whereas the corresponding decrease in Ki67 expression in tumors expressing HMGCR in the pre-treatment sample was 24 % (P = 0.02). Furthermore, post-treatment Ki67 expression was inversely correlated to post-treatment HMGCR expression (rs = -0.42; P = 0.03). Findings from this study suggest that HMGCR is targeted by statins in breast cancer cells in vivo, and that statins may have an anti-proliferative effect in HMGCR-positive tumors. Future studies are needed to evaluate HMGCR as a predictive marker for the selection of breast cancer patients who may benefit from statin treatment.}},
  author       = {{Bjarnadottir, Olöf and Romero, Quinci and Bendahl, Pär-Ola and Jirström, Karin and Rydén, Lisa and Loman, Niklas and Uhlén, Mathias and Johannesson, Henrik and Rose, Carsten and Grabau, Dorthe and Borgquist, Signe}},
  issn         = {{1573-7217}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{499--508}},
  publisher    = {{Springer}},
  series       = {{Breast Cancer Research and Treatment}},
  title        = {{Targeting HMG-CoA reductase with statins in a window-of-opportunity breast cancer trial.}},
  url          = {{http://dx.doi.org/10.1007/s10549-013-2473-6}},
  doi          = {{10.1007/s10549-013-2473-6}},
  volume       = {{138}},
  year         = {{2013}},
}