title: Prediagnostic aspirin use and mortality in women with stage I to III breast cancer: A cohort study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
abstract: BACKGROUND
  There is a body of evidence indicating that aspirin may reduce the risk of cancer mortality. However, to the authors' knowledge, the optimal exposure timing and mechanism of action remain unclear. In the current study, the authors investigated associations between prediagnostic aspirin use and breast cancer-specific mortality in a US population.
  
  
  METHODS
  Postmenopausal women diagnosed with stage I to III breast cancer (1993-2009) were identified (2925 women with a total of 18,073 person-years) from the National Cancer Institute's Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Prediagnostic aspirin use (1274 women) was identified from study questionnaires. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) for associations between aspirin use and breast cancer-specific mortality. Effect modification by lymph node status was evaluated.
  
  
  RESULTS
  Prediagnostic aspirin use was not found to be associated with lower breast cancer-specific mortality (HR, 0.95; 95% CI, 0.68-1.31 [P = .74]). In analyses stratified by lymph node status, aspirin use was found to be associated with lower breast cancer-specific mortality among women with lymph node-negative tumors (HR, 0.54; 95% CI, 0.32-0.93 [P = 0.02]), but not those with lymph node-positive tumors (HR, 1.41; 95% CI, 0.92-2.16 [P = 0.11]). Tests for interaction were found to be statistically significant (P for interaction =.006). No association was noted between aspirin use and lymph node status.
  
  
  CONCLUSIONS
  Prediagnostic aspirin use was not found to be associated with a reduction in breast cancer-specific mortality overall. However, effect modification by lymph node status was observed and mortality was found to be reduced by approximately one-half among aspirin users with lymph node-negative disease. This represents a clinically significant reduction in breast cancer mortality. These findings contribute to the understanding of aspirin's mechanism of action in breast cancer. However, further etiologic research to understand this association is warranted. Cancer 2016;122:2067-75. © 2016 American Cancer Society.
authors.affiliation: Clinical and Translational Epidemiology Branch, Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Bradley
authors.affiliation: Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Amanda
authors.initials: A
authors.lastname: Black
authors.affiliation: Clinical and Translational Epidemiology Branch, Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Freedman
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Thomas I
authors.initials: TI
authors.lastname: Barron
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008875:Middle Aged; D017698:Postmenopause; D016016:Proportional Hazards Models
chemical_list: D001241:Aspirin
keywords: Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial; aspirin; breast cancer mortality; lymph node metastasis; postmenopausal