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Aspirin and Cancer Prevention

November 1, 2012
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Illustrative Case Series

By Jerome W. Yates, MD. Hematology/Immunology Unit, National Institute on Aging, National Institutes of Health. Dr. Yates reports no financial relationships relevant to this field of study.

A 62-year-old Caucasian woman returns to her primary care physician for a follow-up visit after routine colonoscopy and is accompanied by her 63-year-old husband. The gastroenterologist had resected three adenomatous polyps and suggested a repeat colonoscopy in 1 year. She is presently taking no daily medicines and is in good health, and her physician suggested that she might consider taking aspirin (either 325 mg or if that dose caused gastrointestinal symptoms an 81 mg enteric-coated tablet, daily). He had explained that there was now evidence that such treatment is associated with diminished polyp development and colon cancer, as well as reduced cardiovascular disease in individuals taking daily prophylactic aspirin.

Her husband then inquired whether he should be taking aspirin for the same reasons, but particularly to prevent prostate cancer. He is concerned because his younger brother (age 62) just died from metastatic prostate cancer, and although there was no definitive diagnosis his 84-year-old father may have had prostate cancer.

Their physician said that daily aspirin was the most cost-effective way of preventing some cardiovascular disease and selected cancers, and he would suggest they both consider this approach while being cognizant of potential "bleeding problems" and the need for routine follow-up because both had risk factors for cancer deserving professional attention.

Discussion

Hippocrates (460 B.C-377 B.C.) left records that a powder from the leaves and bark of willow trees could be used to treat pain and fever, and 19th century scientists found the active ingredient to be salicin. Subsequent extractions of salicin yielded salicylic acid, which caused gastritis when ingested and required buffering to become acetyl salicyclic acid (aspirin). Beyond pain relief and its antipyretic properties, aspirin has been found to decrease platelet adhesion and thereby diminish platelet clumping and clot formation. Preclinical studies have shown that aspirin inhibits cyclooxygenase (particularly COX-2 isoform), an enzyme found to be overexpressed in some cancer cells. Whereas the mechanisms by which COX-2 influences cancer development and growth is incompletely understood, there is evidence that it plays a role in carcinogenesis, cancer growth, apoptosis, and blood vessel formation.1 In a recent meta-analysis of 139 observational studies,2 the investigators conclude that published observational studies when taken in aggregate demonstrate a beneficial role of aspirin on colorectal and other digestive tract cancers and modest risk reductions for breast and prostate cancer. However, the authors point out the significant heterogeneity across studies and that dose-risk and duration-risk relationships still remain unclear.

This patient presented above had three adenomatous polyps and had no history of taking aspirin regularly in the past. In an earlier meta-analysis of randomized trials examining aspirin as a chemopreventive agent for patients with colorectal adenomas, the data would seem to support the recommendation by her physician.3 Inasmuch as adenomatous polyps are considered premalignant, aspirin treatment in this situation may, indeed, be preventing occult colorectal cancer at its earliest stage of development. Along with the follow-up colonoscopy, the suggestion for aspirin chemoprevention for this patient is reasonable if well tolerated.

The situation for her husband presents a different set of questions:

  1. 1. Is this a case of familial prostate cancer?
  2. 2. Are there clinical differences besides risk for sporadic and familial prostate cancer?
  3. 3. Do aspirin or other anticoagulants play a role in prostate cancer prevention and/or its clinical course?

In the case of the patient's husband, there is an increased probability that there may be a familial risk because of the relatively young age of his brother who had prostate cancer to which his death was attributed. The presence of a suggestive clinical diagnosis of prostate cancer in the elderly father, who was a nursing home resident, should serve as an indication closer follow-up of the patient's husband. Fatal familial prostate cancers may represent a subgroup, because some familial prostate cancer patients demonstrate good survival following diagnosis.4 The largest cohort studies suggest a statistically significant risk reduction for incident prostate cancers among aspirin users.2 Daily aspirin reduces the risk for developing metastases and dying from prostate cancer based on information extracted from randomized controlled trials.5 With demonstrable efficacy in the presence of overt disease, it is an unproven but logical extrapolation to expect benefit in limiting incident prostate cancers or the rate of progression of covert disease.

In summary, both wife and husband may benefit from daily aspirin exposure in the attempt to prevent cancer and cardiovascular disease. There are risks of chronic aspirin treatment and these should be considered when treating otherwise healthy individuals.

References

1. Khan Z, et al. Biology of Cox-2: An application in cancer therapeutics. Curr Drug Targets 2011;12:1082-1093.

2. Bosetti C, et al. Aspirin and cancer risk: A quantitative review to 2011. Ann Oncol 2012;23:1403-1415.

3. Cole BF, et al. Aspirin for the chemoprevention of colorectal adenomas: Meta-analysis of the randomized trials. J Natl Cancer Inst 2009;101:256-266.

4. Alberti C. Hereditary/familial versus sporadic prostate cancer: Few indisputable genetic differences and many similar clinicopathological features. Eur Rev Med Pharmacol Sci 2010;14:31-41.

5. Rothwell PM, et al. Effect of daily aspirin on risk of cancer metastasis: A study of incident cancers during randomised controlled trials. Lancet 2012;379:1591-1601.