title: Recent prediagnostic aspirin use, lymph node involvement, and 5-year mortality in women with stage I-III breast cancer: a nationwide population-based cohort study.
abstract: Lymph node-positive breast tumors are more likely to express COX2 than node-negative tumors. In preclinical studies, COX2 inhibition prevents breast tumor spread to lymph nodes. Therefore, we examined the association between recent (1 year) prediagnostic use of aspirin (COX1/COX2 inhibitor), lymph node involvement at breast cancer diagnosis, and breast cancer-specific mortality. Women with stage I-III breast cancer diagnosed from 2001 to 2006 (N = 2,796) were identified from Ireland's National Cancer Registry. These data were linked to prescription refill and mammographic screening databases. Relative risks (RR) were estimated for associations between prediagnostic aspirin use and lymph node-positive status at diagnosis. HRs were estimated for associations between pre- and postdiagnostic aspirin use and 5-year mortality, stratified by lymph node status. Women with prediagnostic aspirin use were statistically significantly less likely to present with a lymph node-positive tumor than nonusers [RR = 0.89; 95% confidence interval (CI), 0.81-0.97], particularly those with larger (Pinteraction = 0.036), progesterone receptor (PR)-negative (Pinteraction < 0.001) or estrogen receptor (ER)-negative (Pinteraction = 0.056) tumors. The magnitude of this association increased with dose (Ptrend < 0.01) and dosing intensity (Ptrend < 0.001) and was similar in women with or without screen-detected tumors (Pinteraction = 0.70). Prediagnostic aspirin use was associated with lower 5-year breast cancer-specific mortality among women with lymph node-negative tumors (HR, 0.55; 95% CI, 0.33-0.92) but not node-positive tumors (HR, 0.91; 95% CI, 0.37-1.22). Tests for effect-modification were, however, not statistically significant (Pinteraction = 0.087). Postdiagnostic aspirin use was not associated with breast cancer-specific mortality (HR, 0.99; 95% CI, 0.68-1.45). Our findings indicate that recent prediagnostic aspirin use is protective against lymph node-positive breast cancer. This is a plausible explanation for reductions in breast cancer mortality reported in observational studies of aspirin use.
authors.affiliation: Department of Pharmacology and Therapeutics, Trinity College, University of Dublin, Dublin; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Thomas I
authors.initials: TI
authors.lastname: Barron
authors.affiliation: Department of Pharmacology and Therapeutics, Trinity College, University of Dublin, Dublin;
authors.forename: Evelyn M
authors.initials: EM
authors.lastname: Flahavan
authors.affiliation: National Cancer Registry Ireland, Cork, Ireland;
authors.forename: Linda
authors.initials: L
authors.lastname: Sharp
authors.affiliation: Department of Pharmacology and Therapeutics, Trinity College, University of Dublin, Dublin;
authors.forename: Kathleen
authors.initials: K
authors.lastname: Bennett
authors.affiliation: Department of Medical Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine; and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland kvisvan1@jhu.edu.
authors.forename: Kala
authors.initials: K
authors.lastname: Visvanathan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000401:mortality* / Q000473:pathology*; D015331:Cohort Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D016861:Cyclooxygenase Inhibitors; D001241:Aspirin
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