Lymph node-positive breast tumors are more likely to express COX-2 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) pre-diagnostic 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 2001-2006 (N=2,796) were identified from Ireland's National Cancer Registry. This data was linked to prescription-refill and mammographic-screening databases. Relative risks (RR) were estimated for associations between pre-diagnostic aspirin use and lymph node-positive status at diagnosis. Hazard ratios (HR) were estimated for associations between pre- and post-diagnostic aspirin use and 5-year mortality, stratified by lymph-node status. Women with pre-diagnostic aspirin use were statistically significantly less likely to present with a lymph node-positive tumor than non-users (RR=0.89, 95%CI 0.81-0.97), particularly those with larger (P-interaction=0.036), PR-negative (P-interaction<0.001) or ER-negative (P-interaction=0.056) tumors. The magnitude of this association increased with dose (P-trend<0.01) and dosing-intensity (P-trend<0.001) and was similar in women with or without screen-detected tumors (P-interaction=0.70). Pre-diagnostic 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 (P-interaction=0.087). Post-diagnostic aspirin use was not associated with breast cancer-specific mortality (HR=0.99 95%CI 0.68-1.45). Our findings indicate recent pre-diagnostic 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.

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Objective• To examine the association between digoxin exposure and mortality in men with prostate cancer using linked Irish National Cancer Registry and pharmacy claims data. Patients and Methods• Prostate cancer cases were identified from the database and digoxin exposure at prostate cancer diagnosis was identified from prescription claims.• Digoxin users were matched to non-users using a propensity score to identify men with similar cardiovascular comorbidity.• Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between digoxin exposure and all-cause and prostate cancer-specific mortality (PCSM).• Analyses were repeated in the propensity score-matched cohort.• Effect modification of treatment with radiation or androgen-deprivation therapy by digoxin exposure was also assessed. Results• In all, 5732 men with a prostate cancer diagnosis (2001)(2002)(2003)(2004)(2005)(2006) were identified (digoxin exposed, 391). The median follow-up was 4.3 years.• Digoxin exposure was associated with a small non-significant increase in PCSM in the full cohort (HR 1.13, 95% CI 0.91, 1.42) and the propensity. score-matched cohort (HR 1.17, 95% CI 0.88, 1.57).• Adjusted HRs for all-cause mortality were increased for digoxin exposed men (HR 1.24, 95% CI 1.07, 1.43).• Interactions with treatments received were not significant. Conclusions• These results suggest digoxin exposure is not associated with reduced PCSM.• Further investigation of other cardiac glycosides that have shown anti-cancer potential may be warranted.

We found no evidence of an association between low-dose aspirin use before or after diagnosis and risk of prostate cancer-specific mortality, after potential confounders were accounted for, in UK prostate cancer patients.