Daily Aspirin Does Not Yield iDFS Improvement in Stage II/III Breast Cancer

Patients with stage II/III HER2-negative breast cancer who were treated with daily high-dose aspirin did not experience an improvement in invasive disease-free survival.

Treatment with aspirin did not result in an invasive disease-free survival (iDFS) benefit for patients with stage II or III HER2-negative breast cancer with futility established after a short follow-up, according to findings from the phase 3 Alliance 011502 trial (NCT02927249).1

Patients treated with aspirin had a slightly lower survival vs the placebo arm (HR, 1.25; 95% CI, 0.94-1.65; stratified log-rank P = .1258). Investigators reported a total of 111 iDFS events in the aspirin arm (n = 1151) and 90 events in the placebo arm (n = 1510).

“Although this finding was not statistically significant, it approached statistical significance,” according to lead investigator Wendy Y. Chen, MD, MPH, senior physician at Dana-Farber Cancer Institute and assistant profession of medicine at Harvard Medical School.

The rationale for assessing this treatment was supported by in vitro and animal data, which indicated that aspirin and non-steroidal anti-inflammatory agents could decreased breast cancer growth and invasiveness.2

“You will note that there is heterogeneity in those studies,” Chen said. “In the studies that showed no effect, people tended to take a low-dose aspirin, whereas in the studies where there was an effect, people tended to take a high-dose aspirin. This was part of the rationale for us choosing a high-strength aspirin for this trial.”

To enroll on the study, patients were required to be under the age of 70 years with HER2-negative disease. If patients had hormone receptor–positive disease, they needed to be node positive within 10 years of diagnosis; with hormone receptor–negative disease, they needed to be high-risk node negative or node positive within 18 months of diagnosis.

Patients were randomized to receive either 300 mg of aspirin daily or daily placebo for 5 years. Patients were stratified based on hormone receptor status, body mass index (BMI), disease stage, and time since diagnosis. The study’s primary end point was iDFS.

A total of 3021 patients were enrolled across 328 sites from January 2017 to December 2020. The trial had a median follow-up of 24.0 months as of January 14, 2022. Two key trial modifications were implemented to increase accrual, including eligibility for patients with hormone receptor–positive disease in 2018 and allowing remote consents in 2020 in light of the COVID-19 pandemic.

Most patients were either between the ages of 50 to 60 (38.4%) or 60 years or older (24.4%). Additionally, 18.8% of patients were premenopausal and the median BMI was 29 (range, 15-69). In total, 87.5% of patients had a hormone receptor–positive tumor less than 5 years of diagnosis whereas 12.5% were over 5 years out from diagnosis. Eleven percent of patients had a hormone receptor–negative tumor. In terms of race and ethnicity, 81.8% of patients were White, 9.2% were Black, 4.4% were Asian/Pacific Islander, and 0.8% were American Indian or Alaskan. Sixteen men (0.5%) were included in the study.

A total of 191 events were reported at the time of the preplanned interim analysis, which accounted for 50% of the expected events. As of November 2021, the Data Safety Monitoring Board recommended that the study be suspended.

Twelve patients died, including 8 in the aspirin arm and 4 in the placebo arm. Invasive progression was observed in 84 patients in the aspirin cohort and 71 in the placebo cohort, with locally recurrent disease being reported in 23 and 16 patients, respectively, and distant disease in 61 and 55, respectively. Corresponding new primary disease was observed in 19 and 15 patients.

“Compliance was very high in this study and was similar for both aspirin and placebo,” Chen explained. “We also assessed off-protocol aspirin and nonsteroidal anti-inflammatory drug compared with other randomized trials and, again, [findings] were similar for aspirin vs placebo.”

In terms of safety, the most common grade 3 or higher adverse effects (AEs) included vascular (n = 20), gastrointestinal (n = 20), and musculoskeletal (n = 13) toxicities in the aspirin arm vs vascular (n = 21), hematologic (n = 14), and gastrointestinal (n = 11) toxicities in the placebo arm. Grade 4 or higher AEs included 1 event of vascular toxicity in the aspirin arm and 2 events of cardiac toxicity in the placebo arm.


  1. Chen WY, Ballman KV, Winer EP, et al. Randomized phase III, double-blinded, placebo-controlled trial of aspirin as adjuvant therapy for breast cancer (Alliance 011502). Presented at: American Society of Clinical Oncology Plenary Series. February 15, 2022; Virtual. Accessed February 15, 2022.
  2. Liao D, Zhong L, Duan T, et al. Aspirin suppresses the growth and metastasis of osteosarcoma through the NF-κB pathway. Clin Can Res. 2015;21(23):5349-5359. doi:10.1158/1078-0432.CCR-15-0198