Systematic review update of observational studies further supports aspirin role in cancer treatment: Time to share evidence and decision-making with patients?

Abstract

BackgroundEvidence is growing that low-dose aspirin used as an adjuvant treatment of cancer is associated with an increased survival and a reduction in metastatic spread. We therefore extended up to August 2017 an earlier systematic search and meta-analyses of published studies of low-dose aspirin taken by patients with a diagnosis of cancer.MethodsSearches were completed in Medline and Embase to August 2017 using a pre-defined search strategy to identify reports of relevant studies. References in all the selected papers were scanned. Two reviewers independently applied pre-determined eligibility criteria and extracted data on cause-specific cancer deaths, overall mortality and the occurrence of metastatic spread. Meta-analyses were then conducted for different cancers and heterogeneity and publication bias assessed. Sensitivity analyses and attempts to reduce heterogeneity were conducted.ResultsAnalyses of 29 studies reported since an earlier review up to April 2015 are presented in this report, and these are then pooled with the 42 studies in our earlier publication. Overall meta-analyses of the 71 studies are presented, based on a total of over 120 thousand patients taking aspirin. Ten of the studies also give evidence on the incidence of metastatic cancer spread.There are now twenty-nine observational studies describing colorectal cancer (CRC) and post-diagnostic aspirin. Pooling the estimates of reduction by aspirin which are reported as hazard ratios (HR), gives an overall HR for aspirin and CRC mortality 0.72 (95% CI 0.64–0.80). Fourteen observational studies have reported on aspirin and breast cancer mortality and pooling those that report the association with aspirin as a hazard ratio gives HR 0.69 (0.53–0.90). Sixteen studies report on aspirin and prostate cancer mortality and a pooled estimate yields an HR of 0.87 (95% CI 0.73–1.05). Data from 12 reports relating to other cancers are also listed. Ten studies give evidence of a reduction in metastatic spread; four give a pooled HR 0.31 (95% CI 0.18, 0.54) and five studies which reported odds ratio of metastatic spread give OR 0.79 (0.66 to 0.95).ConclusionBeing almost entirely from observational studies, the evidence of benefit from aspirin is limited. There is heterogeneity between studies and the results are subject to important biases, only some of which can be identified. Nevertheless, the evidence would seem to merit wide discussion regarding whether or not it is adequate to justify the recommendation of low-dose therapeutic aspirin, and if it is, for which cancers?

Second cancers in MPN: Survival analysis from an international study

“…We therefore suggest caution in the use of checkpoint inhibitors concurrently with ruxolitinib in MPN patients developing SC. However, a modest reduction of cancer-specific mortality in aspirin users has been widely demonstrated especially for colon cancer but also for breast cancer, hepatocellular carcinoma and other malignant neoplasms 28,29. However, aspirin was a strongly protective agent in the subset of NPPSC, where cause of death was equally distributed between MPN evolution, SC and other causes.…”

Effects of chronic low‐dose aspirin treatment on tumor prevention in three mouse models of intestinal tumorigenesis

“…A considerable body of data from preclinical and clinical studies supports the hypothesis that the unselective cyclooxygenase (COX) inhibitor aspirin could be effective in the prevention of CRC . Furthermore, there is also evidence for a possible role of aspirin in the treatment of CRC and the prevention of metastasis . Although compelling evidence in humans demonstrates that low‐dose aspirin can prevent CRC, the molecular mechanisms are still uncertain.…”

“…4,5 Furthermore, there is also evidence for a possible role of aspirin in the treatment of CRC and the prevention of metastasis. [6][7][8][9][10][11] Although compelling evidence in humans demonstrates that low-dose aspirin can prevent CRC, the molecular mechanisms are still uncertain. Generally, two different modes of chemoprevention can be distinguished: COX-dependent and -independent mechanisms.…”

Epigenetics and differential effects of aspirin on breast cancer survival: Opportunities for understanding human susceptibility and risk

“…[8][9][10][11][12][13][14][15][16] Several mechanisms with both clinical and laboratory evidence support this possibility. [8][9][10][11][12][13][14][15][16] Several mechanisms with both clinical and laboratory evidence support this possibility.…”

“…16,20 Early cohort studies found that aspirin was protective for breast cancer overall, but not for ER-negative and PR-negative tumors. 16,20 Early cohort studies found that aspirin was protective for breast cancer overall, but not for ER-negative and PR-negative tumors.…”