*For medical professionals only
Aspirin has been rumored to be a "miracle drug" in the market.
Its path to "godhood" is inseparable from a large number of observational and retrospective scientific studies that have found that taking aspirin is associated with a reduced risk of cancer progression or death.
The types of cancer covered in those studies were many, including breast cancer, which is the second most common cancer in the world [1]. If the efficacy of aspirin on breast cancer is as found in a retrospective study, it will be good news for the millions of new breast cancer patients diagnosed each year worldwide. However, there are no placebo randomized controlled clinical studies that can confirm the anti-cancer effect of aspirin on breast cancer.
Unfortunately, the "myth" created by aspirin in a retrospective study was shattered in the world's first placebo randomized controlled clinical study for breast cancer.
Recently, a research team led by Wendy Y. Chen of the Dana-Farber Cancer Institute published a blockbuster study in the Journal of the American Medical Association (JAMA), a top medical journal [2].
They initiated a randomized, placebo-controlled, double-blind3 clinical trial that was originally planned to last for five years, but at an interim analysis with a median follow-up of 33.8 months, they found that the number of events such as death and aggressive progression was unusually higher in the 300 mg daily aspirin group compared with the placebo control group (not statistically significant). As a result, this clinical study was forced to be terminated.
Chen et al. argue that in patients with high-risk non-metastatic breast cancer, daily aspirin does not improve the risk of recurrence or survival of breast cancer, and aspirin should not be recommended as an adjuvant treatment for breast cancer.
Summary of the study
To find out the true clinical effects of aspirin, oncologist Chen and her team recruited 3,020 patients with high-risk, non-metastatic breast cancer at 534 research sites in the United States and Canada from January 6, 2017 to December 4, 2020. The patients ranged in age from 23 to 69 years, with a median age of 53 years, of whom 16 were male.
All subjects were randomly assigned to aspirin (300 mg daily) and placebo control in a 1:1 ratio, and the trial was planned to run for 5 years. The primary endpoint of the study is invasive disease-free survival (IDFS), defined as the time from randomization to the first occurrence of any of the following: distant recurrence, local recurrence, ipsilateral or contralateral breast cancer, second primary (non-mammary) invasive cancer, or death due to any cause. The secondary endpoint is overall survival (OS).
Baseline characteristics of patients in both groups
At the median follow-up of 33.8 months, there were 253 IDFS events at the interim analysis, including 141 in the aspirin group and 112 in the placebo group, with a 27% increase in risk in the aspirin group, but this was not statistically significant (HR, 1.27; P=0.06). With the exception of contralateral breast cancer, all IDFS events, including death, invasive progression (distant and local), and new primary cancer events, occurred more in the aspirin group, but the difference was not statistically significant.
In terms of secondary endpoints, there were 63 deaths and 46 deaths from breast cancer in the aspirin group and 52 deaths and 35 deaths from breast cancer in the placebo group, but the difference was not statistically significant (HR, 1.19; P=0.36).
Primary and secondary endpoints of the study
From the above study data, it is not difficult to see that oral aspirin 300mg daily has no benefit in breast cancer IDFS in high-risk early-stage breast cancer patients. Chen and her colleagues believe that although the follow-up period was short, the pre-set invalidation threshold was crossed, so the likelihood of benefit from additional follow-up was very low.
It is important to note that while this study suggests no benefit of aspirin in breast cancer patients, aspirin may still have an important role in preventing and treating other cancers.
For example, a 2020 double-blind, randomized, placebo-controlled study published in The Lancet found that taking aspirin for more than 2 years in people at high risk of bowel cancer (Lynch syndrome) with inherited mutations reduced the incidence of bowel cancer by 50%, and even worse, the protective effect of aspirin lasted for up to 20 years [3].
Therefore, the effectiveness of aspirin in fighting cancer depends on randomized controlled clinical studies conducted in specific cancers.
Bibliography:
[1]. Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012; 379(9826):1591-1601. doi:10.1016/S0140-6736(12)60209-8
[2]. Chen WY, Ballman KV, Partridge AH, et al. Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer: The Alliance A011502 Randomized Trial. JAMA. Published online April 29, 2024. doi:10.1001/jama.2024.4840
[3]. Burn J, Sheth H, Elliott F, et al. Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial. Lancet. 2020; 395(10240):1855-1863. doi:10.1016/S0140-6736(20)30366-4
本文作者丨BioTalker