Abstract

Abstract Background Inhibition of the cyclooxygenase (COX) / prostaglandin pathway has been shown to suppress the development of lymphatic metastases in animal models of breast cancer. A recent population based study reported that women with pre-diagnostic aspirin use (COX1/COX2 inhibitor) were significantly less likely to present with a lymph node metastasis at diagnosis than non-users. Pre-diagnostic aspirin use was also associated with lower 5-year breast cancer-specific mortality among women with lymph node-negative tumors. This study aims to confirm these results in a US population. Objective To examine the association between pre-diagnostic aspirin use, lymph node metastasis at breast cancer diagnosis, and breast cancer mortality, among women in the Prostate Lung Colorectal and Ovarian (PLCO) screening trial. Methods Women with stage I-III breast cancer were identified in PLCO. Pre-diagnostic aspirin use was ascertained from a self-reported questionnaire completed at trial entry. Adjusted risk ratios (RR) were calculated for associations between pre-diagnostic aspirin use and lymph node-positive status at diagnosis. Adjusted hazard ratios (HR) were estimated for associations between pre-diagnostic aspirin use at baseline and mortality, stratified by lymph node status. Ever vs never use of aspirin was examined and analyses incorporating updated measures of aspirin exposure are ongoing. Results There were 2925 women with stage I-III breast cancer, 716 of whom had lymph node metastases at diagnosis. Median time between assessment of pre-diagnostic aspirin exposure and diagnosis was 70 months. Aspirin users (n = 1274) were more likely than non-users (n = 1651) to have a greater number of comorbidities (p = 0.005) and were also more likely to be current or former smokers (p = 0.008). No association was observed between pre-diagnostic aspirin use and lymph node involvement at diagnosis RR 1.06 (95% CI 0.93-1.19). Pre-diagnostic aspirin use was not associated with lower breast cancer specific mortality HR 0.86 (0.60-1.23). However, in analyses stratified by lymph node status at diagnosis aspirin use was associated with lower breast cancer-specific mortality among women with lymph node-negative tumors (HR = 0.48, 95%CIs 0.27- 0.88), but not lymph node-positive tumors (HR 1.30 95%CIs 0.81- 2.09). Tests for effect-modification were statistically significant (P-interaction = 0.0001). Conclusion These data suggest that in women using aspirin prior to a breast cancer diagnosis, negative nodal status predicts a subsequent survival benefit from aspirin use.They partly reflect the findings in the previous study and may contribute to the understanding of aspirin's potential mechanism of action in breast cancer progression. However further etiologic research to understand this association is warranted. Citation Format: Marie C. Bradley, Amanda Black, Andrew N. Freedman, Robert N. Hoover, Kala Visvanathan Visvanathan, Thomas I. Barron. Pre-diagnostic aspirin use, lymph node involvement and mortality in women with stage I-III breast cancer: A study in the Prostate Lung Colorectal and Ovarian cancer screening trial. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 878. doi:10.1158/1538-7445.AM2015-878

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