(203) Low-dose aspirin prescriptions and risk of breast cancer recurrence: a Danish nationwide cohort study with up to 23 years of follow-up

Publication Number: 536

Background: Low-dose aspirin irreversibly inhibits platelet aggregation through inhibition of the cyclooxygenase enzymes COX-1 and COX-2. Platelets are thought to facilitate tumorigenesis by promoting tumor cell survival and metastatic growth. 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 early breast cancer during 1996-2004 as registered in the Danish Breast Cancer Group (DBCG) database. We obtained information on aspirin prescriptions (≥2 prescriptions filled between cancer diagnosis and selected survival landmarks) from the Danish National Prescription Registry. Information on recurrence (local, regional or distant recurrent cancer, excluding contralateral breast cancers) was obtained using the DBCG database (recurrence within 10 years) and a previously validated algorithm (recurrence ≥ 10 years after diagnosis) derived from data in the Danish National Patient Registry, the Danish Pathology Registry, the Danish Cancer Registry and a contralateral breast cancer database. We calculated cumulative incidences of breast cancer recurrence and death. 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, and 15 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, and concurrent medications. We followed patients until recurrence, death, second cancer, loss to follow-up, or 31 December 2018.

Results: We included 21,684 women diagnosed with breast cancer. During 245,309 person-years of follow-up, 4,939 patients experienced breast cancer recurrence. Our landmark analyses showed a slightly reduced hazard of recurrence in the 5-, 10-, and 15-year landmark cohort (5-year landmark adjusted HR = 0.81, 95% CI = 0.67-0.98; 10-year landmark adjusted HR = 0.88, 95% CI = 0.74-1.06; 15-year landmark adjusted HR = 0.81, 95% CI = 0.57-1.15). Longer duration of aspirin use was associated with a reduced risk of recurrence. Aspirin users experienced lower cumulative incidence of breast cancer recurrence, but higher cumulative incidence of death compared with non-users.

Conclusions: We found a slightly reduced risk of breast cancer recurrence in aspirin users compared with nonusers. This is likely due to residual confounding and competing risks given the higher cumulative incidence of death in aspirin users.