title: Statin prescriptions and breast cancer recurrence risk: a Danish nationwide prospective cohort study.
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.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Rm 355, Boston, MA 02115, USA. nhtpa@channing.harvard.edu
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Ahern
authors.forename: Lars
authors.initials: L
authors.lastname: Pedersen
authors.forename: Maja
authors.initials: M
authors.lastname: Tarp
authors.forename: Deirdre P
authors.initials: DP
authors.lastname: Cronin-Fenton
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Garne
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Silliman
authors.forename: Henrik Toft
authors.initials: HT
authors.lastname: Sørensen
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Lash
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000473:pathology / Q000517:prevention & control*; D003718:Denmark / Q000453:epidemiology; D011307:Drug Prescriptions / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000188:drug therapy; D016014:Linear Models; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000517:prevention & control*; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D055502:Secondary Prevention; D019821:Simvastatin / Q000008:administration & dosage*
chemical_list: D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin