by Dr. C.H. Weaver M.D. updated 8/2022
Non-steroidal anti-inflammatory drugs (NSAIDS) are medicines that are used for the treatment of a wide range of musculoskeletal illnesses including spinal disorders, osteoarthritis and inflammatory conditions like rheumatoid arthritis. NSAIDs effectively relieve pain, inflammation, and fever. A number of treatment guidelines for osteoarthritis, rheumatoid arthritis, and chronic low back pain recommend the use of NSAIDs for extended periods of time.
Like all medicines, NSAIDs are associated with potential side effects including hypertension and gastrointestinal bleeding. Analyses of cardiovascular trials evaluating NSAID "cardio-protective" effects suggested that aspirin may also have a viable role in cancer prevention. In fact, evidence from comparative trials suggests that a daily dose of aspirin (75mg or more) might decrease the risk of developing cancer - suggesting an approximately 20% reduction in overall cancer incidence between three and five years after initiation of aspirin use and a 30 percent reduction during follow-up more than five years later.10
Doctors from Denmark published a report on a potential benefit of the prolonged use of low-dose aspirin and NSAIDs. Danish physicians evaluated the use of low-dose aspirin or other NSAIDs and colorectal cancer. In the studied population from Northern Denmark, 10,280 cases of cancer were compared to 102,800 controls in regard to aspirin or NSAID drug use. Continuous long-term use of aspirin (greater than 5 years) was associated with a 27% reduction in colorectal cancer risk. Continuous long-term non-aspirin NSAIDs use was associated with a 43% decreased risk. The decrease in risk was noted in particular with NSAIDs with high cyclooxygenase-2 inhibition like celecoxib.8
This observation was confirmed in a recently published systematic review and meta-analysis of all the published observational studies on aspirin and digestive tract cancers published through March 2019 which included 113 studies, including 45 that looked specifically at colorectal cancer risk. The analyses found that regular use of aspirin reduces the risk for several cancers and there is increased benefit with longer duration of use, and higher doses.1
- Regular aspirin reduces the risk of developing colon, esophageal, stomach, pancreatic and some liver cancers.2,7,9
- Regular aspirin use did not appear associated with a reduced risk for developing head and neck cancer.
- An aspirin dose of 75 mg to 100 mg per day conferred a 10% reduction in risk for colorectal cancer, whereas a dose of 325 mg per day conferred a 35% reduction and a dose of 500 mg per day conferred a 50% reduction.
- Results also showed inverse duration-risk relationships between aspirin use and developing cancer.
Although the inherent biases of observational studies serves as a limitation to this and similar studies the analyses seems to support a beneficial effect of aspirin for the prevention of colon and other cancers of the digestive tract. These study results are consistent with a previous large analyses published in JAMA Oncology that found regular aspirin use reduced the risk of colorectal cancer by 19 percent and the risk of any gastrointestinal cancer by 15 percent.
Researchers affiliated with the American Cancer Society also evaluated data from individuals participating in the Cancer Prevention Study II Nutrition Cohort. This study included nearly 7,000 men and over 7,600 women who enrolled between 1992 and 1993. Aspirin use was reported along with overall cancer incidence as well as the incidence of 10 specific cancers.
- Among individuals who used adult-strength aspirin for five or more years, men had a 16% reduced risk of developing cancer compared with those who never used aspirin and women had a 14% reduced risk of developing cancer compared with those who never used aspirin.
- Daily adult-strength aspirin use carried a 32% reduced risk of developing colorectal cancer among men and women combined, a 19% reduced risk of prostate cancer among men, and a 17% reduced risk of breast cancer among women.
USPSTF advises against aspirin for primary CVD prevention for adults 60 years or older
The U.S. Preventive Services Task Force does not recommend aspirin for primary stroke and heart disease prevention in adults aged 60 years or older and considers the use of aspirin for primary prevention in adults aged 40 to 59 years at high risk for CVD should be considered on a case-by-case basis. This new recommendation is different from those issued by the task force in 2016, which supported aspirin for primary prevention in adults aged 50 to 59 with a 10-year CVD risk of at least 10% and stated adults aged 60 to 69 with a 10-year CVD risk of at least 10% could be considered for aspirin for primary prevention on a case-by-case basis.
Since the prior recommendation three studies suggested the benefits of aspirin for primary prevention of CVD may not outweigh the risks, and the American College of Cardiology and American Heart Association issued a primary prevention guideline that advised against the use of aspirin for primary prevention except in patients at very high CVD risk.
To evaluate the benefits of aspirin for primary prevention of CV morbidity and mortality, the task force pooled the results of 13 randomized clinical trials, which included a total of 161,680 participants. The findings from of the pooled analysis indicated that aspirin for the primary prevention of CVD is associated with decreased risk for MI and stroke but not CV or all-cause mortality. Moreover, findings were similar when trials using various doses of aspirin were compared with studies of low-dose aspirin. The Task Force recommendation is not for people already taking aspirin for a previous heart attack or stroke; they should continue to do so unless told otherwise by their clinician.
Aspirin and NSAIDs appear to reduce the risk of developing certian cancers and individuals at high risk for those cancers shoudl discuss the potential benefits of "an aspirin a day" with their physician. Individuals should consider taking aspirin to reduce their risk of colorectal cancer, particularly those with other reasons for regular use, such as heart disease prevention, but the risk benefit increases with age due to aspirin related bleeding side effects. Because aspirin carries risks of its own and is not suitable for everyone, individuals should discuss the potential benefits and risk of aspirin with their treating physician in the context of an overall health plan that includes heart and other preventable diseases.17
Melanoma & Skin Cancers
Skin cancer is the most commonly diagnosed cancer in the United States, with more than one million new diagnoses each year. The most common types of skin cancer are basal cell carcinoma and squamous cell carcinoma. Melanoma is a less common form of skin cancer, but tends to be more aggressive.
Women who regularly take aspirin may also have a reduced risk of developing melanoma. In previous studies the impact of NSAIDs on the risk of melanoma has been inconsistent. When researchers analyzed data from the Women’s Health Initiative Study the study analysis indicated that women who took aspirin regularly had a 21 percent reduced risk of melanoma compared to non-aspirin users. Aspirin’s protective effect increased over time—the researchers found that there was an 11 percent reduced risk at one year, a 21 percent reduced risk between one and four years, and as much as a 30 percent reduced risk at five years and beyond. The use of non-aspirin NSAIDs was not associated with reduced melanoma risk.11,12
Researchers from Denmark evaluated all skin cancers between 1991 and 2009 including 1,974 cases of squamous cell carcinoma; 13,316 cases of basal cell carcinoma; and 3,242 cases of malignant melanoma in comparison to nearly 179,000 population controls—with 10 controls matched to each case by age, gender, and country of residence. They measured the use of aspirin and other NSAIDs through a prescription database.
The results indicated that individuals who had ever used NSAIDs were 15 percent less likely to develop squamous cell carcinoma and 13 percent less likely to develop malignant melanoma compared to those who did not use NSAIDs. Long-term use (7 or more years) and high-intensity use was associated with an even stronger effect.15 Researchers from Australia have reported similar findings.16
The regular use of non-steroidal anti-inflammatory drugs may also reduce the risk of benign prostatic hyperplasia as well as prostate cancer. Studies have reported that...
- Men who had used aspirin or ibuprofen at least twice a week for more than a month had a 33% lower risk of prostate cancer than men who did not use aspirin or ibuprofen.
- Men with a specific variant of the LTA gene were more likely than other men to benefit from aspirin or ibuprofen. Use of aspirin or ibuprofen reduced the risk of prostate cancer by 57% among men with the variant, and did not significantly reduce the risk of prostate cancer among men without the variant.
The researchers conclude that genotype may influence the protective effect of NSAIDS on prostate cancer.The second study evaluated the effect of NSAID use on BPH. Researchers conducted a study among 2,447 men in Olmsted County, Minnesota.
- Daily NSAID use was linked with a 27% reduction in the likelihood of moderate or severe urinary symptoms.
- Daily NSAID use reduced the risks of low urinary flow rate, increased prostate size, and elevated PSA by roughly half.
In a more recent study, researchers analyzed data from 5,955 men in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database. All of the men had localized prostate cancer and were treated with surgery or radiation. Over one-third of the men (37%) were taking anticoagulants—most commonly, aspirin. The researchers found that after a median follow-up of 70 months, the risk of death from prostate cancer was significantly lower in the group of men taking aspirin compared to their counterparts. In fact, those taking aspirin were less than half as likely to die from prostate cancer over a 10-year period—the prostate cancer death rate among the men taking aspirin was 3 percent compared to 8 percent among the men who were not. Men taking aspirin were also significantly less likely to experience disease recurrence or cancer spread to the bones. The researchers concluded that regular aspirin use is associated with reduced prostate cancer-specific mortality.
NSAIDS Aspirin and Breast Cancer
The use of non-steroidal anti-inflammatory drugs (NSAIDS), including both aspirin and ibuprofen, appears to significantly reduce the risk of developing breast cancer. Researchers recently conducted a large meta-analysis including results from several studies exploring the potential association between the use of NSAIDs and the risk of breast cancer. The analysis included over 2,788,000 women, and separate analyses were conducted for ibuprofen and aspirin use.
- NSAID use was associated with a 12% reduction in breast cancer incidence.
- Use of aspirin and ibuprofen yielded similar results in risk of breast cancer.
According to another study published in Breast Cancer Research regular use of aspirin may modestly reduce the risk of developing hormone-positive breast cancer. Breast cancer is one type of cancer for which research continues to explore a potential association between NSAID use and incidence. Because the mechanism through which NSAIDs work include the suppression of estrogen, researchers speculated that NSAID use may reduce the risk of hormone-positive breast cancer. Hormone-positive breast cancer, also referred to as estrogen receptor (ER)-positive breast cancer, is the most common type of breast cancer and is stimulated to grow from exposure to the female hormones estrogen and/or progesterone.
Researchers evaluated data from the National Institutes of Health–AARP Diet and Health Study, which included 127,383 female AARP (formerly known as the American Association of Retired Persons) members. Participants were aged 51 to 72 years, had no history of cancer, and completed questionnaires that included information regarding use of NSAIDS and breast cancer incidence.
- There was no overall association between the use of NSAIDS and breast cancer.
- Regular aspirin use reduced the risk of hormone-positive breast cancer by 16%.
- Aspirin and other NSAID use did not demonstrate a reduced risk of hormone-negative breast cancer.
- NSAIDS other than aspirin did not demonstrate a reduced risk of hormone-positive breast cancer.
The researchers concluded: “Breast cancer risk was not significantly associated with NSAID use, but daily aspirin use was associated with a modest reduction in ER-positive breast cancer. Our results provide support for further evaluating relationships by NSAID type and breast cancer subtype.”
Researchers from Dana-Farber Cancer Institute and Brigham and Women’s Hospital (BWH) have received a $10 million Breakthrough Award from the Department of Defense’s Office of the Congressionally Directed Medical Research Program to test whether aspirin helps women with breast cancer avoid recurrence and live longer. This is the first ever randomized trial in the United States testing aspirin in the disease, which impacts more than 3 million American women who are living with a breast cancer diagnosis.
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The Aspirin for Breast Cancer (ABC) Trial is recruiting 3,000 women with Stages II and III breast cancer to participate in the study. Women participating in the trial will be randomly assigned to receive aspirin or a placebo pill.
Previous observational research, where scientists observe peoples’ behavior, and correlate that behavior with their health, has found that breast cancer survivors who were regular aspirin users had a 50 percent lower risk of breast cancer recurrence and death compared to those who did not use aspirin. This, along with other promising preclinical research, has led to intense interest among physicians and survivors to explore the therapeutic benefits of aspirin.
“This trial is the first of its kind in United States,” said Eric Winer, MD, Director of Breast Oncology Program, Professor of Medicine, and Thompson Chair of Breast Cancer Research at Dana-Farber Cancer Institute. “The potential benefits of aspirin in preventing breast recurrence are significant and we look forward to determining if aspirin could augment current therapies. This is a treatment that needs to be evaluated further,” emphasized Dr. Winer, who is also a Partnering PI of the grant.
Aspirin and Risk of Stomach Cancer
Regular aspirin use may reduce the risk of distal stomach cancer (cancer in the lower part of the stomach).
Cancer of the stomach is called gastric cancer. Gastric adenocarcinoma is the most common type of stomach cancer. It arises from cells that line the surface of the stomach. An important risk factor for gastric cancer is infection with the bacterium Helicobacter Pylori (H. pylori).
Although the frequency of gastric cancer has been declining, rates of gastric cancer remain high in many parts of the world. Because of the number of people affected and the generally poor prognosis of gastric cancer, researchers continue to search for ways to prevent the disease.
Non-steroidal anti-inflammatory drugs (NSAIDS) include drugs such as aspirin and ibuprofen. These drugs are commonly used to reduce inflammation and relieve pain, but research suggests that NSAIDS may also reduce the risk of certain types of cancer.
To explore the relationship between NSAID use and risk of stomach cancer, researchers evaluated information from a study known as the Multiethnic Cohort Study. Study participants were enrolled in Hawaii and Los Angeles. During the study, 643 study participants were diagnosed with stomach cancer.
Information about aspirin and non-aspirin NSAID use was collected by self-administered questionnaire.
- Regular aspirin use was linked with a 27% reduction in risk of distal stomach cancer (cancer in the lower part of the stomach).
- Non-aspirin NSAID use did not influence the risk of stomach cancer.
This study suggests that regular aspirin use may reduce the risk of distal stomach cancer. Because regular aspirin use also carries some risks, however, people who are considering taking aspirin on a regular basis are advised to talk with their physician.21
Aspirin and NSAIDS - Protective Against Esophageal Cancer?
Aspirin or nonsteroidal anti-inflammatory drugs (NSAIDS) may provide a protective effect against the development of esophageal cancer.
Aspirin and NSAIDS such as celecoxib have been under recent evaluation in the treatment and/or prevention of various cancers. Researchers from California recently evaluated data from 9 clinical studies performed from 1998 to 2000 involving aspirin or NSAID use and esophageal cancer. The data indicated that an individual’s use of aspirin or NSAIDS resulted in reduced incidences of both squamous cell and adenocarcinoma esophageal cancer. More frequent use of aspirin or NSAIDS related to a larger reduction in the risk of developing esophageal cancer; however, even intermittent use of these agents provided a reduced risk of esophageal cancer. Aspirin provided a greater protective effect against esophageal cancer than NSAIDS.
These researchers concluded that the use of aspirin/NSAIDS may significantly reduce the risk of developing esophageal cancer. Individuals may wish to speak with their physician about the results of this data. Furthermore, use of these agents comes with associated risks and individuals should always speak with their physician prior to use of any medication.22
Aspirin as Ovarian Cancer Prevention? Research Says Maybe
Some evidence suggests that an aspirin a day may reduce the risk of ovarian cancer but more research is needed before your doctor will routinely prescribe it for prevention.23,24
A study, conducted by the National Cancer Institute (NCI), found that women who take aspirin daily might have 20 percent reduced risk of ovarian cancer, and an even greater reduction with low-dose aspirin.23
Another study published in the Journal of Clinical Oncology also found that frequent aspirin use may lower the risk of ovarian cancer in individuals with multiple risk factors.
Ovarian Cancer Risk Factors
- Family history
- mutations in the BRCA 1 and 2 genes
To evaluate the role of aspirin the researchers’ pooled data from 17 clinical studies evaluating aspirin that included more than 8,300 patients.
The researchers found that daily, or almost daily, aspirin use was associated with a 13% reduction in ovarian cancer risk and that aspirin benefitted most subgroups. Importantly, this research provides further evidence that ovarian cancer chemoprevention with frequent aspirin use could benefit people in higher-risk subgroups.
This study is consistent with other research - The Iowa Women’s Health Study also found that regular aspirin use may reduce the risk of developing ovarian cancer but did not appear to affect the risk of endometrial cancer.24
To evaluate the link between aspirin and non-aspirin NSAIDS and risk of ovarian and endometrial cancer researchers evaluated information from the Iowa Women’s Health Study. The study began in 1992 and enrolled roughly 20,000 women between the ages of 58 and 76 years.
During 15 years of follow-up, 311 study participants were diagnosed with endometrial cancer and 167 were diagnosed with ovarian cancer.
- Compared with women who reported no use of aspirin, risk of ovarian cancer was 17% lower among women who used aspirin less than two times per week, 23% lower among women who used aspirin between two and five times per week, and 39% lower among women who used aspirin six or more times per week.
- Use of non-aspirin NSAIDS did not affect the risk of ovarian cancer
- Neither aspirin nor non-aspirin NSAIDS affected the risk of endometrial cancer.
It’s still too early in the research process to accept aspirin as a proven preventive measure against ovarian cancer. In other words, researchers on the study don’t recommend that physicians start prescribing it as such just yet.
And be wary of starting your own daily aspirin regimen, whether for ovarian cancer of other diseases. Regular use of aspirin can cause severe side effects (including internal bleeding), so you’ll want to discuss daily use with your doctor.
For now it’s good to know that if you’ve doctor has already approved daily aspirin to reduce your risk of other diseases, you may also be taking a step toward preventing ovarian cancer.
- Bosetti C, et al. Ann Oncol.2020;doi:10.1016/j.annonc.2020.02.012.
- Cao Y, Wu K, Wang M, et al. Population-wide Impact of Long-term use of Aspirin and the Risk for Cancer. Jama Oncology. Published online March 3, 2016. doi:10.1001/jamaoncol.2015.6396.
- Rothwell PM, Fowkes FG, Belch JF, et al. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. The Lancet. 2011;377:31-41.
- Jacobs E, Thun M, Bain E, et al. A large cohort study of long-term daily use of adult-strength aspirin and cancer incidence. Journal of the National Cancer Institute. 2007; 99: 608-615.
- Zhang X, Smith-Warner SA, Collins LC, et al. Use of aspirin, other nonsteroidal anti-inflammatory drugs, and acetaminophen and postmenopausal breast cancer incidence. Journal of Clinical Oncology. Published early online August 27, 2012. doi: 10.1200/JCO.2012.42.2006
- Choe KS, Cowan JE, Chan JM, et al. Aspirin use and the risk of prostate cancer mortality in men treated With prostatectomy or radiotherapy. Journal of Clinical Oncology. Published early online August 27, 2012. doi: 10.1200/JCO.2011.41.0308
- British Journal of Cancer, Vol 84, No. 7, pp. 965-968, 2001
- Friis S et al. Low-dose aspirin or nonsteroidal anti-inflammatory drug use and colorectal cancer risk. Ann Intern Med 2015;163:347-35
- Tan X-L, Reid Lombardo KM, Bamlet WR, Robinson DP, Anderson K, Petersen GM. Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen and risk of pancreatic cancer. Presented at the 102nd Annual Meeting of the American Association for Cancer Research (AACR), April 2-6, 2011, Orlando, FL. Abstract 1902.
- Thun MJ, Jacobs EJ, Patrono C. The role of aspirin in cancer prevention. Nature Reviews Clinical Oncology. Published early online April 3, 2012. doi:10.1038/nrclinonc.2011.199
- Liu X, Plummer SJ, Nock NL, Casey G, Witte JS. Nonsteroidal Antiinflammatory Drugs and Decreased Risk of Advanced Prostate Cancer: Modification by Lymphotoxin Alpha. American Journal of Epidemiology. Early Online Publication August 24, 2006.
- St. Sauver JL, Jacobson DJ, McGree ME, Lieber MM, Jacobsen SJ. Protective Association between Nonsteroidal Antiinflammatory Drug Use and Measures of Benign Prostatic Hyperplasia. American Journal of Epidemiology. Early Online Publication August 11, 2006.
- Gamba CA, Swetter SM, Stefanick ML, et al. Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women. Cancer. Published early online March 11, 2013: DOI: 10.1002/cncr.27817.
- Rothwell PM, Price JF, Fowkes FGR et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits n 51 randomised controlled trials. Lancet. Early online publication March 21, 2012.
- Johannesdottir SA, Chang ET, Mehnert F, et al. Nonsteroidal anti-inflammatory drugs and the risk of skin cancer: A population-based case-control study. Cancer. Published early online May 29, 2012. DOI: 10.1002/cncr.27406
- Butler GJ, Neale R, Green AC, et al. Nonsteroidal anti-inflammatory drugs and the risk of actinic keratoses and squamous cell cancers of the skin. *Journal of the American Academy of Dermatology.*2005;53:966-972.
- Task Force Issues Draft Recommendation Statement on Aspirin Use to Prevent Cardiovascular Disease. https://www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/aspirin-use-to-prevent-cardiovascular-disease-preventive-medication. Published and accessed Oct. 12, 2021.
- Gierach G, Lacey J, Schatzkin A, et al. Nonsteroidal anti-inflammatory drugs and breast cancer risk in the National Institutes of Health-AARP Diet and Health Study. Breast Cancer Research [early online publication]. April 30, 2008. *DOI:*doi:10.1186/bcr2089.
- Takkouche B, Regueira-M?ndez C, Etminan M. Breast Cancer and Use of nonsteroidal anti-inflammatory drugs: a meta-analysis. Journal of the National Cancer Institute [early online publication]. October 2008. DOI: 10.1093/jnci/djn324.
- Holmes MD, Chen WY, Li L et al. Aspirin intake and survival after breast cancer. Journal of Clinical Oncology [early online publication]. February 16, 2010.
- Epplein M, Nomura AMY, Wilkens LR, Henderson BE, Kolonel LN. Nonsteroidal anti-inflammatory drugs and risk of gastric adenocarcinoma: The Multiethnic Cohort Study. American Journal of Epidemiology. 2009; 170:507-14.
- Corley D, Kerlikowske K, Verma R, Buffler P. Protective association of aspirin/NSAIDS and esophageal cancer: a systematic review and meta-analysis.Gastroenterology. 2003;124:47-56.
- Trabert B, Ness RB, Lo-Ciganic WH, et al. Aspirin, Nonaspirin Nonsteroidal Anti-inflammatory Drug, and Acetaminophen Use and Risk of Invasive Epithelial Ovarian Cancer: A Pooled Analysis in the Ovarian Cancer Association Consortium. Journal of the National Cancer Institute. 2014;106 (2):doi:10.1093/jnci/djt431.
- Society of Gynecologic Oncologists, 32nd Annual Meeting, March 2-7, 2001)
- Acta Obstetricia et Gynecologica Scandinavica. 2012; 91(9): 1094-1102.
- Prizment AE, Folsom AR, Anderson KE. Nonsteroidal anti-inflammatory drugs and risk for ovarian and endometrial cancers in the Iowa Women’s Health Study. Cancer Epidemiology, Biomarkers, and Prevention. 2010;19:435-442.