Abstract P4-03-02: Low-dose aspirin prescriptions and breast cancer recurrence: a Danish nationwide cohort study with up to 23 years of follow-up
Authors: Solmunde Elisabeth , Pedersen Rikke N , Nørgaard Mette , Mellemkjær Lene , Friis Søren , Ejlertsen Bent , Ahern Thomas P. , Cronin-Fenton Deirdre 
Published: March 2023

Abstract
Background Low-dose aspirin irreversibly inhibits the cyclooxygenase enzymes COX-1 and COX-2, which catalyze the formation of prostaglandins and thromboxanes, inhibiting platelet aggregation. Platelets are thought to play a role in tumorigenesis. As such, aspirin may have a beneficial effect on breast cancer prognosis, but results to date are conflicting. Objectives To evaluate the association between aspirin use and breast cancer recurrence up to 23 years after primary diagnosis. Methods We included all women diagnosed with non-metastatic breast cancer during 1996-2004 registered in the Danish Breast Cancer Group (DBCG) clinical database. We obtained information on aspirin prescriptions (&gt;= 2 prescriptions filled between cancer diagnosis and the landmark) from the Danish National Prescription Registry. Information on early and late (&gt;10 years after primary diagnosis) recurrence was obtained using the DBCG database (for recurrence within the first 10 years after diagnosis) and for late recurrence via a previously described and validated algorithm, drawing on data from the Danish National Patient Registry, the Danish Pathology Registry, the Danish Cancer Registry and a contralateral breast cancer database. We used Cox regression to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CI) employing landmark analyses starting follow-up at years 5, 10, 15, and 20 after primary diagnosis. We adjusted for potential confounders including calendar year of diagnosis, menopausal status, comorbidities, estrogen receptor status, clinical stage, grade, surgery type, chemo- and endocrine therapy, diagnostic codes for alcoholism and obesity, as well as co-medications (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, bisphosphonates, metformin, digoxin, hormone replacement therapy, non-steroidal anti-inflammatory drugs, and vitamin K antagonists). We followed patients until recurrence, death, second cancer, loss to follow-up, or 31 December 2018. Results Among 21,684 women with non-metastatic breast cancer, 4,902 experienced recurrence during 242,427 person-years of follow-up. Our landmark analyses showed a reduced hazard of recurrence in the 5-, 10-, and 15-year landmark cohorts (5-year landmark adjusted HR = 0.80, 95% CI = 0.68, 0.94; 10-year landmark adjusted HR = 0.84, 95% CI = 0.71, 1.00, 15-year landmark adjusted HR = 0.83, 95% CI = 0.61, 1.14). The 20-year landmark analysis revealed an adjusted HR of 1.09 (95% CI = 0.49, 2.46). Conclusions The potential anti-cancer effect of aspirin appears most pronounced in the first 15 years after breast cancer diagnosis. Funding Elisabeth Solmunde is funded by the Danish Cancer Society (R320-A18464-B5768) and the Independent Research Fund Denmark (1149-00013B). This work was supported by grants to Deirdre Cronin-Fenton from the Danish Cancer Society (“Knæk Cancer” R147-A10100).
Citation Format: Elisabeth Solmunde, Rikke N Pedersen, Mette Nørgaard, Lene Mellemkjær, Søren Friis, Bent Ejlertsen, Thomas P. Ahern, Deirdre Cronin-Fenton. Low-dose aspirin prescriptions and breast cancer recurrence: a Danish nationwide cohort study with up to 23 years of follow-up [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-02.