Daily Aspirin Fails to Improve Disease-Free Survival in Breast Cancer

Wendy Y. Chen, MD, MPH

Although prior research has suggested that daily aspirin use may have antitumor effects, a recent study found no difference in invasive disease–free survival between patients with HER2-negative breast cancer who took a full-strength aspirin daily and those who did not. “Although inflammation may still play a key role in cancer, it’s also important to remember that aspirin may have different effects in other cancers, such as colon, or in a different setting, such as primary vs secondary prevention,” study author Wendy Y. Chen, MD, MPH, a medical oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts, explained during a presentation of the data.

The study (NCT02927249), which was presented at the February 2022 American Society of Clinical Oncology (ASCO) Plenary Series,¹ included more than 3000 patients under 70 years with HER2-negative breast cancer who were randomly split into 2 groups: half received 300 mg of aspirin every day, and the other received a placebo (FIGURE 1 ). The main goal of the study was to compare invasive disease–free survival. “Aspirin users had a slightly worse survival than those patients who received placebo,” Chen said. Findings showed that the aspirin users had a higher amount of disease events than the placebo group (111 compared with 90, respectively), although the difference was not statistically significant and the types of events were relatively balanced between the 2 groups, the investigators explained.

There was also a similar amount of severe AEs between the arms. “The incidence of grade 3 or higher [AEs] was similar for aspirin vs placebo. Further, there were no grade 4 cardiac, hematologic, or gastrointestinal events in the aspirin group,” Chen said.

However, another expert involved in the ASCO Plenary Series noted that the characteristics of the patient population may play a role in the outcomes that were observed. “From these data, we can conclude that this high event rate among a postmenopausal, overweight population who had hormone receptor– positive, high-risk disease was to be expected. And this is exactly the group that one would want to try to intervene upon, because we’d expect this group to have high levels of inflammation,” said Angela DeMichele, MD, MSCE, coleader of the Breast Cancer Research Program and director of the Breast Cancer Clinical Trials Unit at Penn Medicine’s Abramson Cancer Center in Philadelphia, Pennsylvania.

Additionally, DeMichele pointed out that about 44% of patients dropped out in the early stages of the trial, although the reasons why were not made known and could be interesting to consider. Study participants reported on whether they were adherent to taking their aspirin or placebo daily, and DeMichele noted, “Self-report can be notorious for overestimates of adherence.”

Despite potential reasons for the poorer aspirin outcomes, this was not the first study to show that aspirin use may not improve cancer-related outcomes.

In 2018, findings from the Aspirin in Reducing Events in Elderly trial (ASPREE; NCT01038583)1 were published, and they showed worse outcomes for patients who were over age 70 years and who took daily aspirin.

“Aspirin users [in the ASPREE trial] were found to have an increased risk of death—that was mainly driven by increased risk of cancer deaths. Of note, 19% had a prior history of cancer,” Chen said.

The United States Preventive Services Task Force recommends daily aspirin for the prevention of colorectal cancer in individuals aged 50 to 59 years who have a 10-year cardiovascular risk of 10% or higher. However, the jury is out when it comes to the risks and benefi ts of aspirin use in older adults.

“What we can take away from this study... is that at this time, aspirin should not be used simply to prevent breast cancer recurrence. For those situations in which there are other options, decisions about aspirin use for other indications should include an individualized risk/benefit discussion between physician and patient,” DeMichele said.

REFERENCE

1. Chen WY, Ballman KV, Winer EP, et al. A randomized phase III, double-blinded, placebo-controlled trial of aspirin as adjuvant therapy for breast cancer (A011502): the aspirin after breast cancer (ABC) trial. Presented at: ASCO Plenary Series. Accessed February 24, 2022. https:// bit.ly/3haWSPZ