Targeting HMG-CoA reductase with statins in a window-of-opportunity breast cancer trial
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)…
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Statins have high first-pass metabolism, allowing tumors to escape and produce their own cholesterol.
“However, statins have a high first-pass metabolism, allowing for tumors to escape and produce their own cholesterol (11, 12).”
From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [11]
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“However, a robust upregulation of HMGCoA-reductase, the enzymatic target of statins, was also observed [12,13].”
Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells
Bendre, S. V., Wang, Y., Hajyousif, B., K C, R., Bhogale, S. G., Pradeep, D., Krawczynska, N., Schane, C. P., Weisser, E., Singh, A., et al. (2026) · Science Advances · doi:10.1126/sciadv.adx5490 · Cited by 8 · see citing works
“However, statins have a high first-pass metabolism, allowing for tumors to escape and produce their own cholesterol ( 13 , 14 ).”
- Authors
- Bjarnadottir, O., Romero, Q., Bendahl, P.-O., Jirström, K., Rydén, L., Loman, N., Uhlén, M., Johannesson, H., Rose, C., Grabau, D., & Borgquist, S.
- Affiliations
- Lund University (SE)
- Science for Life Laboratory (SE)
- AlbaNova (SE)
- Corresponding author
- Borgquist, Signe
- Venue
- Breast Cancer Research and Treatment
- Published
- 2013-03-08
- Volume
- 138
- Issue
- 2
- Pages
- 499-508
- ISSN
- 0167-6806 (ISSN-L)
- 1573-7217
- OpenAlex
- W2159313433
- Cited by
- 230
- References
- 4
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 14 · 2023: 17 · 2022: 18 · 2021: 19 · 2020: 24 · 2019: 15 · 2018: 17 · 2017: 18 · 2016: 24 · 2015: 21 · 2014: 16 · 2013: 5
- FWCI
- 7.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Breast Cancer Research and Treatment (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- HMG-CoA reductase, statins, atorvastatin, breast cancer, mevalonate pathway, Ki-67, tumor cell proliferation, predictive biomarkers, statin response, window-of-opportunity trial
- MeSH terms
- Atorvastatin, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Breast Neoplasms, Combined Modality Therapy, Female, Heptanoic Acids, Humans, Hydroxymethylglutaryl CoA Reductases, Middle Aged, Pyrroles, Biomarkers, Tumor, Gene Expression, Treatment Outcome, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Ki-67 Antigen, Cell Proliferation
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