Statin Use and Reduced Cancer-Related Mortality

Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
New England Journal of Medicine (Impact Factor: 55.87). 11/2012; 367(19):1792-802. DOI: 10.1056/NEJMoa1201735
Source: PubMed


A reduction in the availability of cholesterol may limit the cellular proliferation required for cancer growth and metastasis. We tested the hypothesis that statin use begun before a cancer diagnosis is associated with reduced cancer-related mortality.
We assessed mortality among patients from the entire Danish population who had received a diagnosis of cancer between 1995 and 2007, with follow-up until December 31, 2009. Among patients 40 years of age or older, 18,721 had used statins regularly before the cancer diagnosis and 277,204 had never used statins.
Multivariable-adjusted hazard ratios for statin users, as compared with patients who had never used statins, were 0.85 (95% confidence interval [CI], 0.83 to 0.87) for death from any cause and 0.85 (95% CI, 0.82 to 0.87) for death from cancer. Adjusted hazard ratios for death from any cause according to the defined daily statin dose (the assumed average maintenance dose per day) were 0.82 (95% CI, 0.81 to 0.85) for a dose of 0.01 to 0.75 defined daily dose per day, 0.87 (95% CI, 0.83 to 0.89) for 0.76 to 1.50 defined daily dose per day, and 0.87 (95% CI, 0.81 to 0.91) for higher than 1.50 defined daily dose per day; the corresponding hazard ratios for death from cancer were 0.83 (95% CI, 0.81 to 0.86), 0.87 (95% CI, 0.83 to 0.91), and 0.87 (95% CI, 0.81 to 0.92). The reduced cancer-related mortality among statin users as compared with those who had never used statins was observed for each of 13 cancer types.
Statin use in patients with cancer is associated with reduced cancer-related mortality. This suggests a need for trials of statins in patients with cancer.

Full-text preview

Available from:
  • Source
    • "In vitro, preclinical and clinical data shows that lipophilic statins are effective against various cancers including breast cancer [1]–[3]. Recently, Nielsen et al., reported that the mortality rate is significantly decreased in prostate cancer patients treated with statins compared to non-statin users [4]. Lipophilic statins inhibit breast cancer cells (ER positive, HER2 positive and ER negative) growth by decreasing NF-kB, AP-1 activation and phosphorylation of MAPK [5]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Statins are increasingly being recognized as anti-cancer agents against various cancers including breast cancer. To understand the molecular pathways targeted by fluvastatin and its differential sensitivity against metastatic breast cancer cells, we analyzed protein alterations in MDA-MB-231 cells treated with fluvastatin using 2-DE in combination with LC-MS/MS. Results revealed dys-regulation of 39 protein spots corresponding to 35 different proteins. To determine the relevance of altered protein profiles with breast cancer cell death, we mapped these proteins to major pathways involved in the regulation of cell-to-cell signaling and interaction, cell cycle, Rho GDI and proteasomal pathways using IPA analysis. Highly interconnected sub networks showed that vimentin and ERK1/2 proteins play a central role in controlling the expression of altered proteins. Fluvastatin treatment caused proteolysis of vimentin, a marker of epithelial to mesenchymal transition. This effect of fluvastatin was reversed in the presence of mevalonate, a downstream product of HMG-CoA and caspase-3 inhibitor. Interestingly, fluvastatin neither caused an appreciable cell death nor did modulate vimentin expression in normal mammary epithelial cells. In conclusion, fluvastatin alters levels of cytoskeletal proteins, primarily targeting vimentin through increased caspase-3- mediated proteolysis, thereby suggesting a role for vimentin in statin-induced breast cancer cell death.
    Full-text · Article · Sep 2014 · PLoS ONE
  • Source
    • "interfering with cell signaling and apoptosis, which may account, in part, for their antitumor effects [13]. Indeed, statins have been shown to reduce cancer-related mortality in several studies, including the vast survey on the Danish Civil Registration System database [14], and also to reduce the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C [15] or chronic hepatitis B [16]. On the other hand, also mevalonate-independent mechanisms seem to be involved. "

    Preview · Article · Sep 2014 · Journal of Hepatology
  • Source
    • "Compared to treatment with LMWH or Vitamin K antagonists, this would represent an important advantage for patients with cancer, who are at higher risk of haemorrhage during anticoagulant therapy than patients without cancer [33]. There is evidence that statins may even reduce cancer-related mortality [34]. Whenever reporting beneficial effects of chronic medication, the question of therapy adherence also has to be raised. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Patients with cancer are at risk of venous thromboembolism (VTE). Statin-use has been shown to be associated with low risk of VTE in patients without cancer, but data in cancer patients is scarce. The objective of this study was to evaluate the association of statins with risk of VTE in cancer patients in a prospective observational cohort study. Materials and Methods Patients with newly diagnosed cancer or progression of disease after remission were included and prospectively followed for a maximum of 2 years. Study endpoint was occurrence of symptomatic VTE. Results Patients (n = 1434) were followed over a median observation period of 729 days. VTE occurred in 107 (7.5%) patients. At study inclusion, 170 (11.9%) patients took statins. Simvastatin (n = 96) and atorvastatin (n = 48) were the most frequently prescribed statins. VTE occurred in 6 (3.5%) patients with statins. Patients with statins had a lower risk of VTE than patients without (subhazard ratio 0.43, 95% confidence interval 0.19 to 0.98; p = 0.04). In competing risk analysis, the cumulative probability of VTE in patients with statins was 2.94% after 12 months and 3.54% after 24 months, compared to 7.13% and 8.13% in the group without statins (Gray’s test: p = 0.04) Conclusion This study provides observational evidence for an association between statin use and low risk of VTE in patients with cancer. The role of statins for prevention of cancer-associated VTE needs to be confirmed in randomized, controlled trials.
    Full-text · Article · Sep 2014 · Thrombosis Research
Show more