Aspirin Treatment Effect and Association with PIK3CA Mutation in Breast Cancer: A Biomarker Analysis

Studies suggest regular aspirin use decreases breast cancer (BRCA) risk, with high doses exerting an "anti-cancer" effect. Despite reports suggesting aspirin's protective role in BRCA, no findings on aspirin dose association(s) with treatment outcomes have been reported, nor have any molecular subtype associations by which aspirin influences outcomes been elucidated. To interrogate aspirin's effect and determine which populations may benefit from its use, we retrospectively explored data from 1227 patients with BRCA. In this population, 32 used high-dose aspirin (325 mg), 121 used low-dose aspirin (81 mg), and 1074 used no aspirin before and/or after diagnosis.

Several association tests were performed to examine the correlations of clinical variables and PIK3CA mutations from 45 patients with BRCA who used 81 mg of aspirin daily. Kaplan-Meyer survival curves and the log-rank test were utilized to compare survival outcome differences for aspirin dose, usage history, and PIK3CA mutation status. Cox proportional hazards models were used to compute the multivariate hazard ratio (HR) for death.

Patients who regularly used high-dose aspirin (325 mg) had better survival outcomes than those who used low-dose aspirin (81 mg) (HR, 0.094; 95% confidence interval [CI], 0.014-0.62; P = .014). Patients who used aspirin post-diagnosis only achieved significant benefits in overall survival (HR, 0.082; 95% CI, 0.023-0.3; P = 1.39E-04). Also, a subgroup of patients in the low-dose, long-term aspirin group with a PIK3CA mutation showed a small beneficial effect (HR, 0.37; 95% CI, 0.04-3.25; P = .37).

High-dose aspirin after diagnosis may confer BRCA treatment benefits. Future studies should assess the comprehensive mechanism of aspirin for the PIK3CA mutant subgroup in a large study.