Aspirin Use is Associated with Improvement in Distant Metastases Outcome in Patients with Residual Disease after Neoadjuvant Chemotherapy

Abstract

<h3>Purpose/Objective(s)</h3> Previous data has suggested that aspirin (ASA) use may be associated with improved outcomes in patients at higher risk for distant metastases after completion of curative therapy. Patients with breast cancer (BC) that do not obtain a pathologic complete response (pCR), particularly those with residual nodal disease (ypN+) after neoadjuvant chemotherapy (NAC) are at higher risk of worse outcomes. To date, there are no reported studies of potential benefit of ASA use within this subgroup. Our hypothesis is that ASA use can reduce the risk of distant metastases and improve outcome in ypN+ patients after NAC. <h3>Materials/Methods</h3> Patients at two institutions with BC treated with NAC who did not achieve pCR between 2005-2018 were reviewed (IRB protocol STU- 052012-019). Pertinent data, including evidence of ASA use (initiated during remission period), and clinico-pathologic parameters were analyzed. Overall survival (OS), disease free survival (DFS), and distant metastases free survival (DMFS) were obtained using Kaplan Meier analysis. Univariate and multivariate (MVA) logistic regression models were constructed and analyzed. <h3>Results</h3> 637 patients were evaluated, of which 138 were ASA users. Median follow-up for the control group was 3.8 (IQR 2.2-6.3) years and 3.8 (IQR 2.5-6.4) years for the ASA group. Nearly all patients had stage II or III disease (IIA: 75, IIB: 171, IIIA: 120, IIIB: 72, IIIC: 43). 416 patients underwent mastectomy, and 221 patients underwent partial mastectomy. 387 patients were HR+ (hormone receptor positive), 194 HER2+, and 157 were triple negative. 422 patients remained ypN+. The aspirin and non-aspirin groups did not show significant differences in patient characteristics analyzed. Clinico-pathologic characteristics analyzed for association with outcome included age, race, ASA use, molecular profile, pathologic and clinical stage, LVI, and clinical grade. On univariate analysis, ASA use, PR status, ypT, ypN, and clinical stage showed significance for improvements in DMFS, while ASA use, ER/PR status, ypT, ypN, and clinical stage showed significance for improvements in DFS. On MVA, ASA use remained significantly associated with improvements in 5-year DFS (p=.02, 87.0% vs 79.6%) and trended for 5-year DMFS improvement (p=.08, 92.8% vs 89.2%). In the ypN+ patients, ASA use was significantly associated with improvement in 5-year DMFS (p=.03, 85.7% vs 70.7%) on MVA. <h3>Conclusion</h3> Patients at higher risk for worse outcome, particularly those that are unable to achieve nodal clearance after NAC, demonstrated significant outcome benefits with ASA use initiated during remission period. These hypotheses-generating results suggest consideration for development of prospective clinical trials of augmented ASA use in these high-risk BC patients.