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Controlled studies needed to clarify aspirin’s role in cancer prevention
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Aspirin and other inhibitors of COX-2 have a clear impact on multiple aspects of colorectal cancer tumorigenesis.
These include:
Additional studies have suggested the potential for aspirin use to globally reduce the risk for gastroesophageal cancers.
No clear role
Aspirin use has not been recommended as a cancer preventive in the general population.
However, for patients with active cardiovascular disease or those at high risk for cardiovascular disease, guidelines for aspirin therapy now include that its use in such populations conveys a protective benefit with a reduction in the risk for colorectal cancer.
Despite accumulating data to support the potential cancer preventive benefits of aspirin, the role for aspirin therapy in risk reduction for other malignancies — and whether the inclusion of cancer screening impacts these outcomes — have not been clearly identified.
The report by Cao and colleagues in JAMA Oncology provides more than 30-year follow-up on two large population-based prospective patient series — the Nurses’ Health Study and the Health Professionals Follow-Up Study — that included more than 88,000 women and 47,000 men.
The researchers assessed long-term aspirin use, including quantification of dose and duration of usage.
Aspirin use resulted in a modest 3% reduction in the risk for overall cancers. This reduction was driven largely by a 15% lower risk for gastrointestinal cancer, specifically a 19% reduction in the risk for colorectal cancer. Possible benefits also were seen for a reduction in risk for gastroesophageal cancer. The utilization of active colorectal cancer screening attenuated but did not eliminate this benefit.
Results suggested no protective benefit for aspirin therapy against nongastrointestinal cancers.
The researchers estimated that more than 29,000 cases of gastrointestinal cancers could be prevented annually by regular aspirin therapy use. The benefits were both time and dose dependent, with aspirin usage required for at least 6 years or longer, and a minimum use of at least one-half to 1.5 standard aspirin tablets per week.
Mechanistically, the benefit of aspirin as a COX-2 inhibitor makes sense, given the implication of the COX-2 pathway in premalignant precursors of colorectal and gastroesophageal cancers — including polyps — as well as Barrett’s esophagus, and chronic gastritis from various potential causes.
Studies also have indicated that aspirin’s preventive benefit against colorectal cancer may be limited to cancers with particular molecular features.
Early studies that mined data from the pooled Nurses’ Health Study and Health Professionals Follow-Up Study indicated that only cancers with high COX-2 immunohistochemical staining were reduced in incidence. Subsequent studies suggested only cancers with BRAF wild-type status were reduced in incidence.
Studies of patients who underwent curative treatment of colorectal cancer have reached conflicting conclusions about what features in the treated cancer correlate with a preventive benefit of aspirin therapy.
Some studies indicated that only tumors that contained PIK3CA kinase mutations had a reduction in recurrence with subsequent aspirin use. Other studies suggested that human leukocyte antigen class I expression affected the benefit of aspirin use, with no impact of PIK3CA kinase mutation.
Ongoing analyses hopefully will clarify potential biomarkers to identify which patients are most likely to benefit from aspirin therapy.
Impact on practice
How do these updated results impact our practice?
Oncologists routinely recommend aspirin usage in patients after curative treatment of colorectal cancer. Patients who carry the Lynch syndrome gene also should be counseled to take aspirin as a cancer-preventive therapy.
In addition to the utilization of aspirin in high-risk patients with cardiovascular disease, aspirin usage — particularly in patients older than age 40 years — now should at least be a topic of discussion for internists and their patients.
A decision analysis by the U.S. Preventive Services Task Force indicated that, for patients between the ages of 40 and 70 years — in the absence of a risk for stroke or gastrointestinal bleeding — regular low-dose aspirin use should be a consideration for prevention of both cardiovascular disease and colorectal cancer.
Aspirin therapy, however, is not without risks. These include gastrointestinal bleeding and hemorrhagic stroke.
Controlled studies of aspirin as a preventive therapy — including the AspECT trial, a randomized phase 3 study underway in the United Kingdom designed to evaluate esomeprazole with or without aspirin in patients with Barrett’s esophagus — will further clarify the potential risks and benefits of aspirin as a preventive therapy.
References:
Chan AT, et al. N Engl J Med. 2007;356:2131-2142.
Dehmer SP, et al. Ann Intern Med. 2016;doi:10.7326/M15-2129.
Kothari N, et al. Acta Oncol. 2015;doi:10.3109/0284186X.2014.990158.
Liao X, et al. N Engl J Med. 2012;doi:10.1056/NEJMoa1207756.
Nishihara R, et al. JAMA. 2013;doi:10.1001/jama.2013.6599.
For more information:
David H. Ilson, MD, PhD, is chief of the gastrointestinal cancer service at Memorial Sloan Kettering Cancer Center and a professor of medicine at Weill Cornell Medicine. He also is HemOnc Today’s gastrointestinal cancer section editor. He can be reached at Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065; email: ilsond@mskcc.org.
Disclosure: Ilson reports no relevant financial disclosures.