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Cited by 387Cancer, Lipids, and MetabolismMetabolism, Diabetes, and CancerCancer Risks and Factors

Statin Prescriptions and Breast Cancer Recurrence Risk: A Danish Nationwide Prospective Cohort Study

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Ahern, T. P., Pedersen, L., Tarp, M., Cronin-Fenton, D. P., Garne, J. P., Silliman, R. A., Sorensen, H. T., Lash, T. L.·2011·JNCI Journal of the National Cancer Institute
DOI 10.1093/jnci/djr291PMC PMC3186780
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Abstract

BACKGROUND: Accumulating evidence suggests that statins affect diseases other than cardiovascular disease, including cancer, and that these effects may depend on the lipid solubility of specific statins. Though many studies have reported an association between statin use and breast cancer incidence, the relationship between statin use and breast cancer recurrence has not been well studied. METHODS: We conducted a nationwide, population-based prospective cohort study of all female residents in Denmark diagnosed with stage I-III invasive breast carcinoma who were reported to the Danish Breast Cancer Cooperative Group registry between 1996 and 2003 (n = 18,769). Women were followed for a median of 6.8 years after diagnosis. Prescriptions for lipophilic and hydrophilic statins were ascertained from the national electronic pharmacy database. Associations between statin prescriptions and breast cancer recurrence were estimated with generalized linear models and Cox proportional hazards regression with adjustment for age and menopausal status at diagnosis; histological grade; estrogen receptor status; receipt of adjuvant therapy; type of primary surgery received; pre-diagnosis hormone replacement therapy; and co-prescriptions of aspirin, angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, or anticoagulants. All statistical tests were two-sided. RESULTS: Most prescriptions for lipophilic statins in the study population were for simvastatin. Exclusive simvastatin users experienced approximately 10 fewer breast cancer recurrences per 100 women after 10 years of follow-up (adjusted 10-year risk difference = -0.10, 95% confidence interval = -0.11 to -0.08), compared with women who were not prescribed a statin. Exclusive hydrophilic statin users had approximately the same risk of breast cancer recurrence as women not prescribed a statin over follow-up (adjusted 10-year risk difference = 0.05, 95% confidence interval = -0.01 to 0.11). CONCLUSIONS: Simvastatin, a highly lipophilic statin, was associated with a reduced risk of breast cancer recurrence among Danish women diagnosed with stage I-III breast carcinoma, whereas no association between hydrophilic statin use and breast cancer recurrence was observed.

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  • Use of statins is associated with increased time to breast cancer recurrence.

    “use of cholesterol lowering medication (statins) is associated with increased time to breast cancer recurrence (7–9).”

    From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [7]

    The Results section reports a lower 10-year breast cancer recurrence rate among exclusive lipophilic statin users, particularly simvastatin users, consistent with a longer time to recurrence. But hydrophilic statin users had approximately the same recurrence rate as nonusers, so the finding does not support the claim for statins as a whole. Page numbers were not available in our copy. (LLM, conf=0.88)

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Research works printed but not linked: 49

  1. Brown MS, Goldstein JL. Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth. J Lipid Res. 1980;21(5):505-517.
  2. Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45:89-118.
  3. Wang CY, Liu PY, Liao JK. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol Med. 2008;14(1):37-44.
  4. Hamelin BA, Turgeon J. Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol Sci. 1998;19(1):26-37.
  5. Katz MS. Therapy insight: potential of statins for cancer chemoprevention and therapy. Nat Clin Pract Oncol. 2005;2(2):82-89.
  6. Sorensen HT, Riis AH, Lash TL, et al. Statin use and risk of amyotrophic lateral sclerosis and other motor neuron disorders. Circ Cardiovasc Qual Outcomes. 2010;3(4):413-417.
  7. Mann D, Reynolds K, Smith D, et al. Trends in statin use and low-density lipoprotein cholesterol levels among US adults: impact of the 2001 National Cholesterol Education Program guidelines. Ann Pharmacother. 2008;42(9):1208-1215.
  8. Boudreau DM, Yu O, Buist DS, et al. Statin use and prostate cancer risk in a large population-based setting. Cancer Causes Control. 2008;19(7):767-774.
  9. Eliassen AH, Colditz GA, Rosner B, et al. Serum lipids, lipid-lowering drugs, and the risk of breast cancer. Arch Intern Med. 2005;165(19):2264-2271.
  10. Friis S, Poulsen AH, Johnsen SP, et al. Cancer risk among statin users: a population-based cohort study. Int J Cancer. 2005;114(4):643-647.
  11. Setoguchi S, Glynn RJ, Avorn J, et al. Statins and the risk of lung, breast, and colorectal cancer in the elderly. Circulation. 2007;115(1):27-33.
  12. Woditschka S, Habel LA, Udaltsova N, et al. Lipophilic statin use and risk of breast cancer subtypes. Cancer Epidemiol Biomarkers Prev. 2010;19(10): 2479-2487.
  13. Moysich KB, Beehler GP, Zirpoli G, et al. Use of common medications and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2008;17(7):1564-1595.
  14. Cauley JA, McTiernan A, Rodabough RJ, et al. Statin use and breast cancer: prospective results from the Women's Health Initiative. J Natl Cancer Inst. 2006;98(10):700-707.
  15. Boudreau DM, Gardner JS, Malone KE, et al. The association between 3-hydroxy-3-methylglutaryl conenzyme A inhibitor use and breast carci- noma risk among postmenopausal women: a case-control study. Cancer. 2004;100(11):2308-2316.
  16. Bonovas S, Filioussi K, Tsavaris N, et al. Use of statins and breast cancer: a meta-analysis of seven randomized clinical trials and nine observational studies. J Clin Oncol. 2005;23(34):8606-8612.
  17. Browning DR, Martin RM. Statins and risk of cancer: a systematic review and metaanalysis. Int J Cancer. 2007;120(4):833-843.
  18. Dale KM, Coleman CI, Henyan NN, et al. Statins and cancer risk: a meta- analysis. JAMA. 2006;295(1):74-80.
  19. Kuoppala J, Lamminpaa A, Pukkala E. Statins and cancer: a systematic review and meta-analysis. Eur J Cancer. 2008;44(15):2122-2132.
  20. Matsushita Y, Sugihara M, Kaburagi J, et al. Pravastatin use and cancer risk: a meta-analysis of individual patient data from long-term prospec- tive controlled trials in Japan. Pharmacoepidemiol Drug Saf. 2010;19(2): 196-202.
  21. Taylor ML, Wells BJ, Smolak MJ. Statins and cancer: a meta-analysis of case-control studies. Eur J Cancer Prev. 2008;17(3):259-268.
  22. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681.
  23. Kwan ML, Habel LA, Flick ED, et al. Post-diagnosis statin use and breast cancer recurrence in a prospective cohort study of early stage breast cancer survivors. Breast Cancer Res Treat. 2008;109(3):573-579.
  24. Harputluoglu H, Dizdar O, Karaahmet F, et al. Post-diagnosis statin use and breast recurrence sites in early stage breast cancer survivors. Breast Cancer Res Treat. 2008;110(3):541.
  25. Kumar AS, Benz CC, Shim V, et al. Estrogen receptor-negative breast cancer is less likely to arise among lipophilic statin users. Cancer Epidemiol Biomarkers Prev. 2008;17(5):1028-1033.
  26. Garwood ER, Kumar AS, Baehner FL, et al. Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer. Breast Cancer Res Treat. 2010;119(1):137-144.
  27. Campbell MJ, Esserman LJ, Zhou Y, et al. Breast cancer growth prevention by statins. Cancer Res. 2006;66(17):8707-8714.
  28. Katz MS, Minsky BD, Saltz LB, et al. Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer. Int J Radiat Oncol Biol Phys. 2005;62(5):1363-1370.
  29. Kawata S, Yamasaki E, Nagase T, et al. Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized con- trolled trial. Br J Cancer. 2001;84(7):886-891.
  30. Tsai HK, Katz MS, Coen JJ, et al. Association of statin use with improved local control in patients treated with selective bladder preservation for muscle-invasive bladder cancer. Urology. 2006;68(6):1188-1192.
  31. Blichert-Toft M, Christiansen P, Mouridsen HT. Danish Breast Cancer Cooperative Group-DBCG: history, organization, and status of scientific achievements at 30-year anniversary. Acta Oncol. 2008;47(4):497-505.
  32. Moller S, Jensen MB, Ejlertsen B, et al. The clinical database and the treatment guidelines of the Danish Breast Cancer Cooperative Group (DBCG); its 30-years experience and future promise. Acta Oncol. 2008;47(4): 506-524.
  33. Jensen AR, Ewertz M, Cold S, et al. Time trends and regional differences in registration, stage distribution, surgical management and survival of breast cancer in Denmark. Eur J Cancer. 2003;39(12):1783-1793.
  34. Vaughan CJ, Gotto AM Jr. Update on statins: 2003. Circulation. 2004; 110(7):886-892.
  35. Holmes MD, Chen WY, Li L, et al. Aspirin intake and survival after breast cancer. J Clin Oncol. 2010;28(9):1467-1472.
  36. Kwan ML, Habel LA, Slattery ML, et al. NSAIDs and breast cancer re- currence in a prospective cohort study. Cancer Causes Control. 2007;18(6): 613-620.
  37. Wernli KJ, Hampton JM, Trentham-Dietz A, et al. Use of antidepressants and NSAIDs in relation to mortality in long-term breast cancer survivors. Pharmacoepidemiol Drug Saf. 2011;20(2):131-137.
  38. van der Knaap R, Siemes C, Coebergh JW, et al. Renin-angiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/ deletion polymorphism, and cancer: the Rotterdam Study. Cancer. 2008; 112(4):748-757.
  39. Schulman S, Lindmarker P. Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. Duration of Anticoagulation Trial. N Engl J Med. 2000;342(26):1953-1958.
  40. Newcomb PA, Egan KM, Trentham-Dietz A, et al. Prediagnostic use of hormone therapy and mortality after breast cancer. Cancer Epidemiol Biomarkers Prev. 2008;17(4):864-871.
  41. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and valida- tion. J Chronic Dis. 1987;40(5):373-383.
  42. Spiegelman D, Hertzmark E. Easy SAS calculations for risk or prevalence ratios and differences. Am J Epidemiol. 2005;162(3):199-200.
  43. Kubota T, Fujisaki K, Itoh Y, et al. Apoptotic injury in cultured human hepatocytes induced by HMG-CoA reductase inhibitors. Biochem Pharmacol. 2004;67(12):2175-2186.
  44. Hansen PS, Andersen E, Andersen KW, et al. Quality control of end results in a Danish adjuvant breast cancer multi-center study. Acta Oncol. 1997;36(7):711-714.
  45. Ewertz M, Jensen MB, Gunnarsdottir KA, et al. Effect of obesity on prognosis after early-stage breast cancer. J Clin Oncol. 2011;29(1):25-31.
  46. Ozdemir BH, Akcali Z, Haberal M. Hypercholesterolemia impairs angio- genesis in patients with breast carcinoma and, therefore, lowers the risk of metastases. Am J Clin Pathol. 2004;122(5):696-703.
  47. Bosco JL, Silliman RA, Thwin SS, et al. A most stubborn bias: no adjust- ment method fully resolves confounding by indication in observational studies. J Clin Epidemiol. 2010;63(1):64-74.
  48. Friedman GD, Flick ED, Udaltsova N, et al. Screening statins for possible carcinogenic risk: up to 9 years of follow-up of 361,859 recipients. Pharmacoepidemiol Drug Saf. 2008;17(1):27-36.
  49. Kumar AS, Campbell M, Benz CC, et al. A call for clinical trials: lipo- philic statins may prove effective in treatment and prevention of particular breast cancer subtypes. J Clin Oncol. 2006;24(13):2127. author reply 2127-2128.

Cited by

Sorted by citations

Authors
Ahern, T. P., Pedersen, L., Tarp, M., Cronin-Fenton, D. P., Garne, J. P., Silliman, R. A., Sorensen, H. T., & Lash, T. L.
Affiliations
Boston University (US)
ORCID
Venue
JNCI Journal of the National Cancer Institute
Publisher
Oxford University Press (OUP)
Published
2011-08-02
Volume
103
Issue
19
Pages
1461-1468
ISSN
  • 0027-8874 (ISSN-L)
  • 1460-2105
DOI
10.1093/jnci/djr291
PMC
PMC3186780
OpenAlex
W2153810797
Cited by
387
References
0
Citations by year
2026: 8 · 2025: 24 · 2024: 23 · 2023: 20 · 2022: 25 · 2021: 29 · 2020: 41 · 2019: 27 · 2018: 24 · 2017: 28 · 2016: 29 · 2015: 25 · 2014: 31 · 2013: 27 · 2012: 21
FWCI
8.93
Type
journal article
Language
en
Open access
Locations
  • JNCI Journal of the National Cancer Institute (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Aarhus Universitet
  • Aarhus Universitetshospital
  • Karen Elise Jensens Fond
  • National Institutes of Health
  • National Cancer Institute (T32 CA09001, T32-CA-09001-35, R01CA118708, T32CA009001)
  • Congressionally Directed Medical Research Programs
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
  • Health Sciences › Medicine › Oncology › Cancer Risks and Factors
Keywords
statins, breast cancer recurrence, simvastatin, lipophilic statins, hydrophilic statins, statin prescribing, breast cancer, adjuvant therapy, estrogen receptor status, menopausal status, drug repurposing
MeSH terms
Adult, Aged, Anticholesteremic Agents, Breast Neoplasms, Denmark, Female, Humans, Hypercholesterolemia, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Drug Prescriptions, Prospective Studies, Registries, Risk Factors, Linear Models, Proportional Hazards Models, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin, Secondary Prevention

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