An aspirin a day does not keep breast cancer away. Taking aspirin daily did not improve invasive disease-free survival (DFS) in breast cancer patients in a large, randomized prospective trial. Therefore, aspirin should not be used as adjuvant therapy to prevent breast cancer recurrence.
A strong rationale supported a randomized trial of aspirin in breast cancer recurrence. Previous observational studies showed regular aspirin users had a decreased risk of breast cancer death, and randomized controlled trials for other endpoints lent supporting evidence. The Women's Health Study, a primary prevention trial of aspirin, included nearly 40,000 women aged 45 or older who were randomized to aspirin 100 mg daily versus placebo. Results showed a significantly decreased risk of metastatic carcinoma, mainly based on reduced risk of metastatic adenocarcinoma. Pooled analysis of five randomized trials for cardiovascular disease trials also showed similar results in reduction of metastatic breast cancer.
The Aspirin after Breast Cancer (ABC) Trial is the first randomized, placebo-controlled trial to evaluate the efficacy of aspirin in preventing breast cancer recurrence among breast cancer survivors. Lead author Wendy Y. Chen, MD, MPH, Medical Oncologist at the Dana-Farber Cancer Institute, presented the results of the ABC trial at the February 2022 ASCO Plenary Series (Abstract 360922, J Clin Oncol 2022; doi: 10.1200/JCO.2022.40.36_suppl.360922).
Study Details
In this double-blind study, 3,021 patients, all younger than age 70, with high-risk, HER2-negative breast cancer from 338 sites were randomly selected to receive either aspirin (1,511 patients) or a placebo (1,510 patients) daily for 5 years. Median follow-up was 24 months, and the median time on treatment was 18 months.
A preplanned analysis occurred at 50 percent of events. After 191 invasive DFS events (107 in patients taking aspirin and 84 in patients taking placebo) and a median follow-up of 20 months, the stratified hazard ratio comparing aspirin to placebo was 1.27, which is greater than the pre-specified hazard ratio of futility 1.03, and the study was closed early.
There was no difference in the frequency of Grade 3 and 4 adverse events between the study arms. Grade 3 events were found in 7.7 percent in the aspirin arm and 8.3 percent in the placebo arm; Grade 4 events appeared in 1 percent in each arm.
The authors plan to conduct additional analyses on tumor and blood samples collected from participants at baseline and repeat blood samples that were collected at 2 years.
Erika P. Hamilton, MD, ASCO Expert in Breast Cancer and Director of Breast and Gynecologic Cancer Research at Sarah Cannon Research Institute, commented: "These data find that aspirin is likely not a tool we can use to decrease the chance of cancer coming back among estrogen receptor-positive or triple-negative breast cancer patients. However, if people need to be on aspirin for other reasons, they absolutely should take it as it appears to neither help nor hurt breast cancer outcome."
Chen concluded: "In this double-blind, placebo-controlled, randomized trial, there was no benefit of aspirin 300 mg daily on breast cancer invasive DFS. Although follow-up was short, there was a numerically higher number of events in the aspirin arm; therefore, it is unlikely that even with further follow-up there would be any benefit associated with aspirin."
The study strengths include well-balanced intervention arms, a diverse population with strong community support, high compliance, and low off-protocol use of aspirin or NSAIDs. No significant safety concerns were identified.
"Although inflammation may still play a role in cancer progression, aspirin is not recommended for prevention of breast cancer recurrence," said Chen. "Aspirin may have different effects in other cancers (for example, colon cancer) and different settings, primary versus secondary prevention."
ASCO Discussant Angela DeMichele, MD, of the Abramson Cancer Center at the University of Pennsylvania, noted: "This population would have expected to have high levels of inflammation. Patients enrolled were postmenopausal, overweight, with hormone receptor-positive high-risk disease. ABC was a well-designed, well-conducted, randomized controlled trial of aspirin for secondary prevention of breast cancer recurrence and death. It enrolled the right study population given the underlying mechanism of intervention, and patients received adequate administration of study drug with minimal contamination. Although it was not statistically significant, we cannot rule out the potential increase in breast cancer recurrence from aspirin."
Her take-home message for patients and providers was "aspirin should not be used simply to prevent breast cancer recurrence. For those situations where there are other options, decisions about aspirin use for other indications should include an individualized risk/benefit discussion."
She pointed out that the study underscores the need for prospective, randomized controlled trials to isolate effects of interventions identified in observational trials. "One classic example is hormone replacement therapy for cardiovascular disease prevention," DeMichele stated.
Mark L. Fuerst is a contributing writer.