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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.

SUBMITTER: Barron TI

PROVIDER: S-EPMC4523081 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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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.

Barron Thomas I TI Flahavan Evelyn M EM Sharp Linda L Bennett Kathleen K Visvanathan Kala K

Cancer research 20140801 15

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 C ...[more]

PMID: 25085874

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Project description:BACKGROUND:Many studies have suggested that the regular use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, has a protective effect and survival benefit on colorectal cancer (CRC). However, recent data suggest that CRCs have different responses to NSAIDs depending on the timing of NSAID initiation, duration of NSAID use, and molecular characteristics of the tumor. The aim of this study was to evaluate the effect of long-term prediagnostic aspirin use on the prognosis of stage III CRC. METHODS:From 2007 to 2009, patients who were diagnosed with stage III CRC were recruited, and their medical records were retrospectively analyzed. Patients were divided into prediagnostic aspirin users (who used aspirin for more than three months continuously before CRC diagnosis) and non-users (who did not use of aspirin and NSAIDs). The two groups were compared in terms of recurrence, cancer-specific mortality, disease-free survival (DFS), and cancer-specific survival. In an experimental study, three CRC cell lines (Caco2, SW480, and DLD-1) were pretreated with aspirin (1 mM) for four days or 28 days to make aspirin-resistant cells, treated with 5-fluorouracil (5-FU; 2 µM), and apoptosis was measured with flow cytometry using Annexin-V and propidium iodide double staining. RESULTS:Compared with the aspirin non-users (N=565), the prediagnostic aspirin users (N=121) were not different in terms of baseline characteristics including tumor characteristics, except for comorbidities and diabetes medication and statin use, which were higher in the prediagnostic aspirin users. Recurrence and cancer-specific mortality in stage III CRC were significantly higher in prediagnostic aspirin users than non-users (46.7% vs. 32.3%, P=0.003 and 32.2% vs. 19.8%, P=0.003, respectively). Survival analysis using Cox proportional hazards modeling demonstrated that DFS was significantly worse in prediagnostic aspirin users than non-users (HR, 1.525 (1.018-2.286); P=0.041). In cell line experiments, long-term aspirin pretreatment induced an increase in 5-FU-induced apoptosis in SW480 cells compared with control treatment without aspirin pretreatment. However, Caco2 cells showed a significant decrease of apoptosis in the same experiments and no change in DLD1 cells. CONCLUSION:Prediagnostic long-term aspirin use in stage III CRC could be a negative prognostic factor depending on the characteristics of the CRC.

Dataset Information

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.

Publications

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.

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