Marie Bradley

PhD, MPH, MPharm

NCI, DCCPS, CTEB

Cancer prevention fellow

PLCO (Learn more about this study)

PLCO-62

Feb 3, 2014

Pre-diagnostic aspirin use, lymph node involvement and mortality in women with stage I-III breast cancer.

A recent meta-analysis of randomized trials of aspirin for cardiovascular disease prevention suggested the use of aspirin, a cyclooxygenase 2 (cox-2) inhibitor prior to a cancer diagnosis, was associated with a 25% reduction in the risk of distant metastasis at initial tumor presentation and lower cancer specific mortlaity. Importantly, this mortality benefit was only observed among individuals with non-metastatic disease at diagnosis. Similar but non-significant associations between pre-diagnostic aspirin use and reduced mortality were observed for specific cancer sites, including the breast, and observational studies have demonstrated that aspirin use by women with breast cancer has been associated with significant reductions in breast cancer recurrence and mortality.

Lymph node positive breast tumors are more likely to express cox-2 than lymph node negative tumours. Preclinical studies suggest that the cyclooxygenase/prostaglandin pathway is involved in the development of lymph node metastases through the regulation of vascular endothelial growth factor-C/-D (VEGF-C/-D) mediated lymphangiogenesis and have demonstrated that cox-2 inhibition prevents breast tumor spread via lymph nodes. A nationwide population based study in Ireland demonstrated that women with pre-diagnostic aspirin use were significantly less likely to present with a lymph node-positive tumor than non-users (RR=0.89, 95%CI 0.81-0.97), particularly among those with larger (P-interaction=0.036) or PR-negative tumors (P-interaction<0.001). 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 and without screen-detected tumors (P-interaction=0.953). Pre-diagnostic aspirin use was associated with lower breast cancer-specific mortality among women with lymph node-negative tumors (HR=0.53 95%CI 0.30-0.94), but not lymph node-positive tumors (HR=1.02 95%CI 0.75-1.37; P-interaction=0.042). These findings suggest that pre-diagnostic aspirin use is protective against lymph node positive breast cancer and this might explain why aspiirn reduces breast cancer mortality in observational studies. In this study we aim to validate the findings of the Irish study among women in the US PLCO population. PLCO comprises rich and extensive data in the breast cancer supplemental questionnaire as well as information on pre-diagnostic aspirin use which make it an ideal cohort in which to undertake this investigation.