ASA should not be recommended as an adjuvant treatment for breast cancer

Acetylsalicylic acid (ASA) has been hypothesized to affect tumour growth through its antiplatelet and anti-inflammatory effects. Platelets may contribute to metastases in several ways, including promoting tumour angiogenesis, inducing growth factor and cytokine release, and protecting tumour cells from immune cell elimination. Inflammation also induces release of cytokines and growth factors that may promote tumour growth and immune dysregulation. Low-dose ASA (< 100 mg/d) primarily has antiplatelet and antithrombotic effects, while doses ≥ 300 mg/d are required to affect inflammatory pathways.Observational studies of breast cancer survivors and prospective trials of ASA for cardiovascular disease have suggested improved breast cancer survival among regular ASA users. However, prospective studies of ASA to prevent breast cancer recurrence are lacking.To determine whether ASA decreases the risk of invasive cancer events among survivors of breast cancer, a randomized, double-blind, placebo-controlled trial (called A011502), was conducted in the U.S. and Canada. It is believed to be the first randomized, placebo-controlled trial of ASA to report results among survivors of breast cancer. The study included 3,020 participants (age 18 to < 70 years, 99.5% female) with high-risk nonmetastatic breast cancer, enrolled from 534 sites in the United States and Canada. Participants were randomized to receive ASA 300 mg (n=1,510) or placebo (n=1,510) once daily for five years. The 300 mg/d dose was chosen to cover multiple possible mechanisms of action (antiplatelet and anti-inflammatory) rather than to evaluate only the lower (antiplatelet) dose and risk missing a possible clinical effect. The primary outcome was invasive disease–free survival. It was defined as the time from randomization to the first occurrence of any one of the following events: distant recurrence, locoregional recurrence, ipsilateral or contralateral breast cancer, second primary (nonbreast) invasive cancer, or death from any cause. Overall survival was a key secondary outcome.Results showed the following:A total of 3,020 participants had been randomized when the study’s data and safety monitoring committee recommended suspending the study at the first interim analysis because the hazard ratio (HR) had crossed the prespecified futility bound. By median follow-up of 33.8 months, 253 invasive disease–free survival events were observed (141 in the ASA group and 112 in the placebo group), yielding a HR of 1.27 (95% CI, 0.99–1.63; p=0.06). All invasive disease–free survival events, including death, invasive progression (both distant and locoregional) and new primary events, were numerically higher in the ASA group, although the differences were not statistically significant. No significant difference was seen in overall survival (HR, 1.19; 95% CI, 0.82–1.72). Rates of grades 3 and 4 adverse events were similar in both groups.The authors conclude that therapy with ASA 300 mg daily does not improve risk of breast cancer recurrence or survival among patients with high-risk nonmetastatic breast cancer. Patients with a history of early breast cancer should not be encouraged to take ASA as an adjuvant breast cancer treatment to improve their breast cancer outcomes. Reference:Chen WY, Ballman KV, Partridge AH, et al. Aspirin vs placebo as adjuvant therapy for breast cancer. The Alliance A011502 randomized trial. JAMA 2024. Published online April 29, 2024. (accessed May 2, 2024).

ASA should not be recommended as an adjuvant treatment for breast cancer

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