The use of low-dose aspirin among older people shows no effect in reducing the incidence of certain cancer types. However, the treatment — particularly with frequency of at least three times a week — is associated with reductions in mortality in bladder cancer and breast cancer, new observational research shows.
"The results presented here add to the accumulating evidence that aspirin may improve survival for some cancers," the authors write in their cohort study that uses data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The new research was published online January 15 in JAMA Network Open.
"Although prior research has been most heavily concentrated in gastrointestinal cancers, our analysis extends the advantages associated with aspirin use to other cancers, such as bladder and breast cancers," they explain.
In commenting on the study, John J. McNeil, MBBS, PhD, head of the Department of Epidemiology and Preventive Medicine at Monash University in Melbourne, Australia, said the findings, though intriguing, are not necessarily conclusive.
"The data was derived from a very large and well-conducted study," McNeil, who has led other research on aspirin use and the elderly, told Medscape Medical News.
"But these conclusions were drawn from the observational component of the study and therefore potentially confounded by other characteristics that differentiate aspirin users from nonusers."
Aspirin/Cancer Research in Older People Lacking
With well-known reports of decreased risks of heart disease, stroke, cancer — particularly gastrointestinal cancers — and all-cause mortality, as many as 25% to 50% of adults in the US report taking aspirin daily or every other day.
However, evidence of the benefits relating to cancer, specifically in older people, has been inconsistent, with one recent notable study, the randomized, double-blind ASPREE trial, showing no effect of aspirin on cancer incidence, but a higher mortality rate in elderly patients randomly assigned to aspirin for primary prevention.
To further investigate the effects in older patients, first author Holli A.
Loomans-Kropp, PhD, and colleagues with the National Cancer Institute evaluated data on patients who were either 65 years or older at baseline or who had reached aged 65 during follow-up in the PLCO Cancer Screening Trial, which had enrollment from 1993 to 2001.
The authors identified 139,896 individuals with a mean age at baseline of 66.4 years; about half were women and 88.5% were non-Hispanic White.
Follow-up took place until the time of death; December 2014 for those who consented to follow-up; or December 2009 for those who refused consent to follow-up. The authors report that there were 32,580 incident cancers, including 5.4% bladder, 14% breast, 1% esophageal, 1.2% gastric, 2.7% pancreatic, and 2.2% uterine cancers.
The study showed no association between aspirin use and the incidence of any of the cancer types included in the study among those over age 65.
However, further multivariate analysis of survival showed that, with follow-up adjusted to until the time of death, December 31, 2015 or earlier refusal to consent, the use of aspirin at least three times per week was associated with reduced mortality in those with bladder (hazard ratio [HR], 0.67) and breast (HR, 0.75) cancers, whereas no significant associations were observed with esophageal, gastric, pancreatic, or uterine cancer.
A similar association of any aspirin use (less than three times per week) with bladder (HR, 0.75) and breast (HR, 0.79) cancer survival was observed, the authors note.
"These results may indicate that for some cancer types, any aspirin use may be advantageous; however, greater benefit may be observed with increased frequency of use," the authors write.
Mechanism Speculation Focuses on COX-2 Pathway
Theories of the mechanisms behind a potential benefit of aspirin for those with bladder cancer include that urothelial cancer has increased RNA and protein expression of cyclooxygenase-2 (COX-2) and urinary prostaglandin E2, "suggesting upregulation of the COX-2 pathway during cancer progression," the authors write.
In breast cancer, a similar elevated expression of COX-2 has been shown to predict disease outcomes, including progression and decreased survival.
"This may be partly due to the mechanistic interplay between angiogenesis, cell proliferation, apoptosis, and inflammatory processes," the authors note.
The study isn't the first to show a benefit specifically with bladder cancer; other studies include recent research showing that daily aspirin use among patients with bladder cancer was associated with increased 5-year survival following radical cystectomy, the authors note.
Australia's McNeil noted that the new findings from the US researchers, particularly regarding bladder cancer, are of interest. "The reduction in mortality from breast cancer is modest, but the reduction in mortality from bladder cancer was more impressive," he said.
"However, given the fact that this finding is observational data and was a sole finding among multiple comparisons, it must be seen as suggestive rather than proven."
Regarding possible mechanisms, McNeil added that, like the bulk of the prior research, many questions remain.
"There have been many suggestions about ways that aspirin might work at a molecular and cellular level, but no firm consensus has been reached."
The study authors and McNeil have disclosed no relevant financial relationships.
JAMA Network Open. Published January 15, 2021. Full text
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