title: Impact of statin use on cancer recurrence and mortality in breast cancer: A systematic review and meta-analysis.
abstract: Statins have shown antineoplastic properties in preclinical studies with breast cancer cells. They inhibit the enzyme "HMG CoA reductase" and the expression of this enzyme in cancer cells has been implicated as a favorable prognostic factor in patients with breast cancer. After a search of MEDLINE and Embase from inception through November 2015, 817 abstracts were reviewed to identify studies that described an association between statin use and outcomes in breast cancer. A total of 14 studies which included 75,684 women were identified. In a meta-analysis of 10 studies, statin use was associated with improved recurrence-free survival (RFS; HR 0.64; 95% CI 0.53-0.79, I(2)  = 44%). Furthermore, this RFS benefit appeared to be confined to use of lipophilic statins (HR 0.72; 95% CI 0.59-0.89) as hydrophilic statin use was not associated with improvement in RFS (HR 0.80; 95% CI 0.44-1.46). Statin users similarly showed improved overall survival in a meta-analysis with substantial heterogeneity (8 studies, HR 0.66; 95% CI 0.44-0.99, I(2)  = 89%). Statin users also had improved cancer-specific survival, although this relationship was measured with less precision (six studies, HR 0.70; 95% CI 0.46-1.06, I(2)  = 86%). In conclusion, breast cancer patients who use statins, or specifically, lipophilic statins show improved recurrence-free survival. Statin users also had improved overall survival and cancer-specific survival. These findings should be assessed in a prospective randomized cohort and the choice of statin, dose and biomarkers that may predict the efficacy of these drugs should be identified.
authors.affiliation: Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, MO.
authors.forename: Sashidhar
authors.identifier: http://orcid.org/0000-0001-9588-2744
authors.initials: S
authors.lastname: Manthravadi
authors.affiliation: Division of Hematology-Oncology, University of Missouri-Kansas City, Kansas City, MO.
authors.forename: Anuj
authors.initials: A
authors.lastname: Shrestha
authors.affiliation: Division of Hematology-Oncology, University of Missouri-Kansas City, Kansas City, MO.
authors.forename: Sheshadri
authors.initials: S
authors.lastname: Madhusudhana
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D005060:Europe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D009026:Mortality; D009656:North America; D016016:Proportional Hazards Models; D017594:Publication Bias; D012008:Recurrence; D016019:Survival Analysis
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: adjuvant; breast cancer; lipid lowering medications; meta-analysis; statin