No benefit seen for aspirin in breast cancer

Taking aspirin in the adjuvant setting does not appear to lower the risk of recurrence or improve survival in patients with high-risk nonmetastatic breast cancer, as shown in the results of the phase III Alliance A011502 trial.

Over a median follow-up of 33.8 months, the primary endpoint of invasive disease-free survival (IDFS) events did not significantly differ between the aspirin group and the placebo group (hazard ratio [HR], 1.27, 95 percent confidence interval [CI], 0.99–1.63; p=0.06). [JAMA 2024;doi:10.1001/jama.2024.4840]

“All IDFS events, including death, invasive progression (both distant and locoregional), and new primary events, were numerically higher in the aspirin group, although the differences were not statistically significant [compared with the placebo group],” the investigators said.

Results for the secondary endpoint of overall survival were also comparable between the two groups (HR, 1.19, 95 percent CI, 0.82–1.72; p=0.36).

In terms of safety, the rates of grades 3 and 4 adverse events were 9.3 percent in the aspirin group and 10.2 percent in the placebo group, with the difference not reaching significance. None of the patients discontinued study treatment permanently due to grade 3 or higher gastrointestinal bleeding or cardiovascular or vascular events. However, protocol mandated reducing aspirin dose from 300 to 100 mg for grade 2 bleeding or cardiovascular events. Dose reductions for other grade 2 toxicity or grade 1 gastrointestinal and haematologic toxicity were allowed and left to physician discretion. Dose reductions were uncommon and did not differ between groups (2.3 percent vs 2.2 percent).

A total of 3,020 participants (median age 53 years, 81.6 percent White) had been recruited and randomly assigned to receive either 300 mg of aspirin (n=1,510) or placebo (n=1,510) once daily for 5 years when the data and safety monitoring committee recommended suspending the study at the first interim analysis due to futility.

Treatment adherence (taking >80 percent of study doses in the previous 6 months according to medication diaries and pill counts) was high and similar in both groups (12 months: 91.4 percent with aspirin and 89.2 percent with placebo; 24 months: 91.5 percent and 92.1 percent, respectively). And the risk estimates for IDFS and overall survival remained relatively unchanged despite controlling for treatment adherence, as the investigators pointed out.

“Patients with history of early breast cancer should not be encouraged to take aspirin routinely to improve their breast cancer outcomes,” they said.

The null findings for aspirin were consistent with those seen in the ASPREE trial, wherein older adults who received aspirin at 100 mg/d had a higher risk of death than their peers who received placebo (HR, 1.14, 95 percent CI, 1.01–1.29), which was driven by cancer-related deaths (HR, 1.31, 95 percent CI, 1.10–1.56). Furthermore, despite the similar incidence of overall cancer between the two groups (HR, 1.04, 95 percent CI, 0.95–1.14), the aspirin group had a higher risk of developing metastatic cancer and dying due to solid tumours. [N Engl J Med 2018;379:1519-1528; J Natl Cancer Inst 2021;113:258-265]

“Low-grade chronic inflammation has been linked with ageing, so an approach targeting inflammation may be less effective in older individuals. Immune responses are also known to be affected by cancer and older age such that aspirin may interfere with antitumour inflammatory effects in older individuals or people with cancer, leading to a negative association of aspirin with cancer,” the investigators said.

“Also, as noted previously, the cancer-related benefits of aspirin may differ by age because of both host factors and tumour biology,” they said, highlighting evidence from previous studies indicating aspirin to be beneficial in preventing colorectal cancer among Lynch syndrome carriers and with longer-term use. [Lancet 2020;395:1855-1863; JAMA 2022;327:1585-1597]