Aspirin shows no benefit in preventing breast cancer recurrence, study finds

By Vijay Kumar MalesuMay 2 2024Reviewed by Lily Ramsey, LLM

In a recent study published in the JAMA, a group of researchers determined whether aspirin decreases the risk of invasive cancer events among survivors of breast cancer.

Study: Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer. Image Credit: Belkina Margarita/Shutterstock.com

Background 

Several studies have demonstrated aspirin's potential to reduce mortality in breast cancer survivors, with significant evidence from pooled analyses of randomized trials indicating lower risks of metastatic adenocarcinoma among aspirin users.

The Women’s Health Study further supported this by showing long-term aspirin use reduced metastatic cancer risks.

Further research is needed to explore aspirin's potential benefits and mechanisms in cancer therapy, particularly identifying specific patient subgroups who might benefit from its use.

About the study  

The Alliance A011502 trial was conducted in the United States and Canada, a phase 3, randomized, double-blind study. Participants aged 18 to 70 with Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2)-negative breast cancer who had completed standard therapies were randomized to receive either 300 mg of aspirin daily or a placebo.

The study population was stratified by hormone receptor status, body mass index, cancer stage, and time since diagnosis.

Approved by the National Cancer Institute Central Institutional Review Board, the trial mandated informed consent and reviewed safety every six months. 

The trial involved 3020 patients but was halted early due to a lack of significant benefits, as the hazard ratio for disease-free survival between the aspirin and placebo groups was 1.27.

The study also collected blood and urine samples and conducted follow-ups every six months to monitor adherence and adverse effects. Despite rigorous monitoring and adherence to protocol, the trial concluded with no substantial evidence supporting aspirin's effectiveness in reducing breast cancer recurrence. 

Study results 

The present study enrolled 3,020 participants across 534 United States and Canada sites from January 6, 2017, to December 4, 2020. Each participant was randomly assigned either aspirin or placebo, with 1510 in each group.

The trial sought to assess the effectiveness of 300 mg daily aspirin in improving invasive disease-free survival (IDFS) among high-risk, nonmetastatic breast cancer survivors. The participants, aged 23 to 69 years, displayed a diverse demographic and tumor characteristic profile that was well balanced across both groups.

At the point of enrollment, the majority of participants had hormone receptor-positive disease, had undergone chemotherapy, and had a median time from diagnosis to enrollment of around 13 months.

The comprehensive nature of the trial ensured robust monitoring procedures, with an Alliance Data and Safety Monitoring Committee reviewing the trial's conduct and safety biannually. 

The trial reached its first interim analysis in November 2021, where 191 events had been observed. The data showed a hazard ratio of 1.27 for aspirin versus placebo, crossing the prespecified futility boundary and prompting the recommendation to terminate the trial treatments due to lack of significant benefit.

By the median follow-up of 33.8 months, 253 IDFS events had been recorded, with slightly more events in the aspirin group than in the placebo group, but without statistical significance.

Adherence to the medication was high and comparable in both groups, with more than 90% adherence at 12 and 24 months post-enrollment. Off-protocol use of aspirin and nonsteroidal anti-inflammatory drugs was similar between the groups, and rates were consistent with those seen in other placebo-controlled aspirin trials for different diseases.

Adverse events were closely monitored, with no significant difference in the occurrence of severe adverse events between the aspirin and placebo groups. There were a few serious adverse events in the aspirin group, including cardiac and vascular events, but these did not lead to any discontinuation of treatment as per the trial protocol.

Conclusions 

To summarize, in the recent trial, aspirin at 300 mg/day showed no benefit in improving IDFS in patients with high-risk early breast cancer. Despite shorter follow-up, the trial crossed the prespecified futility boundary, suggesting further follow-up was unlikely to change the outcome.

Previous studies hinted at the potential survival benefit of aspirin, particularly from cardiovascular research, suggesting that healthier individuals might continue aspirin use.

However, findings align with the United States Preventive Services Task Force's recommendation against low-dose aspirin for primary cardiovascular prevention in individuals over 60 and parallel outcomes from the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which indicated an increased mortality risk linked to cancer in older aspirin users.