Cancer remains our number two killer, just behind heart disease. Far too many people die each year from cancer of the breast, prostate, colon and lung. What can be done to prevent tumors or keep cancer from spreading? A new study in the journal Open Biology (September 14, 2022) suggests that the lowly aspirin may be able to do that and more for pennies a day.
The Aspirin Story Is Confusing:
Doctors used to love aspirin. Remember the refrain “take two aspirin and call me in the morning”? The idea was that aspirin could solve a lot of minor problems and tincture of time could also be helpful.
More recently, though, many doctors have dissed aspirin. The disrespect has been built on the notion that aspirin is not that helpful against heart attacks or strokes and it can cause bleeding problems. As a result, the United States Preventive Services Task Force (USPSTF) issued these recommendations on April 26, 2022:
“The USPSTF recommends against initiating low-dose aspirin use for the primary prevention of CVD [cardiovascular disease] in adults 60 years or older.
“The decision to initiate low-dose aspirin use for the primary prevention of CVD in adults aged 40 to 59 years who have a 10% or greater 10-year CVD risk should be an individual one. Evidence indicates that the net benefit of aspirin use in this group is small.”
When it came to cancer, the USPSTF added this:
“The evidence is unclear whether aspirin use reduces the risk of colorectal cancer incidence or mortality.”
Aspirin Gets Little to No Respect:
It’s hard to believe that a drug that’s been around for more than 120 years and costs pennies a day could still produce surprising benefits. Let’s face it, cancer remains one of the scariest conditions humans face. If aspirin could prevent cancer or keep cancer from spreading, it should be considered head of the household, rather than a poor cousin.
No other OTC pain reliever has been found to be more effective. And that includes the highly advertised brand name NSAIDs that rely on ibuprofen or naproxen. Unlike these drugs, aspirin does not raise blood pressure, damage the kidneys or increase the risk for blood clots or heart attacks.
Anti-Cancer Activity of Aspirin:
Lest you think this is a brand-new discovery, researchers have been studying aspirin’s power against cancer for over 30 years (New England Journal of Medicine, Dec. 5, 1991).
That’s when investigators from the American Cancer Society reported that:
“Regular aspirin use at low doses may reduce the risk of fatal colon cancer.”
The aspirin review in Open Biology (September 14, 2022) suggests that aspirin may improve cancer survival. The authors analyze data from epidemiologic studies, randomized controlled trials and basic biological research. They conclude that aspirin disrupts key steps in the proliferation of cancer cells. The drug also interferes with the development of blood vessels to feed tumor growth. In addition, there is evidence that aspirin may reduce metastasis through its impact on blood platelets. In other words, aspirin may keep cancer from spreading.
Here is how the scientists describe this research:
“The first evidence of benefit from aspirin in cancer, was the demonstration almost 60 years ago of a reduction in metastatic cancer spread in animal models in vivo which was related to the anti-platelet effect of aspirin. Many authors have since confirmed the association in a range of cancers.”
Randomized controlled trials also reveal a benefit. In the Physicians’ Health Study, men who were taking aspirin were 30% less likely to die from prostate cancer than those taking placebo. Other clinical trials have produced inconsistent results, though the majority do seem to suggest a reduction in mortality.
Observational Studies of Aspirin:
Much of aspirin’s anti-cancer benefit comes from observational studies. There are dozens of such epidemiological reports involving a wide variety of cancers. In general, people taking aspirin appear to be about 20% less likely to die from their cancers.
Here is how the authors describe the overall benefit:
“In the report in 2020, the hypothesis that the benefits of aspirin in the treatment of cancer are relevant to a wide range of cancers was tested in detail in 118 reports based on 18 different cancers. An overall pooled reduction in cancer mortality of about 20% was associated with aspirin taking.”
They also note that aspirin seems to have a broad anti-cancer impact:
“An important finding in this report is that a meta-analysis of the results reported for aspirin in 39 publications focused upon 15 less common cancers (nasopharyngeal, oropharyngeal, oesophagus, gastrointestinal, gastric, rectal, liver, gallbladder, bladder, pancreas, bladder, endometrium, ovary, glioma, head and neck, lung, melanoma) reported overall reductions associated with aspirin (HR 0.79; 0.70, 0.88 in 18 studies, and OR 0.49; 0.26, 0.95 in 5 studies).”
In other words, the cancer reduction ranged from about 12% to more than 50% in these less common cancers.
Aspirin and Mortality:
We have seen commercials for very expensive immunotherapy drugs that make the claim they will help people live longer. It is not clear how much longer. Some of these medications cost over $100,000 a year.
Dr. Vinay Prasad is a professor of epidemiology and biostatistics at the University of California, San Francisco School of Medicine. According to this university, Dr. Prasad is a “practicing Hematologist Oncologist at San Francisco General Hospital and the San Francisco VA Hospital. Dr. Prasad cares for patients with a wide range of medical concerns, including classic hematology, malignant hematology, and solid tumors. He conducts research at the intersection of health policy, evidence based medicine and oncology.”
He wrote a provocative article in The BMJ (Oct. 4, 2017) titled: “Do cancer drugs improve survival or quality of life?” In other words, have our expensive new medicines revolutionized cancer treatment?
According to Dr. Prasad:
“Firstly, when drugs do offer survival advantages, the gains are often marginal.
“Secondly, the small benefits of cancer drugs typically occur in trials conducted in unrepresentative patient populations—patients who are younger and with less comorbidity than average clinical populations. When a marginal drug advantage is applied to a real world population, a small benefit may vanish entirely because of the fine balance between risks and benefits typical of these agents.
“Finally, many of the surrogate outcomes used for drug approval are poorly correlated with survival. For others, the strength of the correlation is untested.”
You can listen to our interview with Dr. Prasad at this link. In it he discusses this topic in more understandable language.
What About Aspirin and Duration of Cancer Survival?
The new analysis in Open Biology states:
“A few authors have made estimates of the length of additional survival associated with aspirin taking. A number of different summary statistics of survival have been used, and these defy pooling, but they are listed elsewhere and they range from about three months up to three years. Using a different approach, a group in Liverpool extracted extensive baseline data, including aspirin taking, from the records for 44 000 patients with colon cancer. With these they constructed a formula giving predicted estimates of survival. Entering the details for a typical non-diabetic subject aged 70 with colon cancer into the formula, the inclusion of aspirin increases the estimate of survival by about five years for a man, and for a woman, about 4 years.”
Not all studies show that aspirin will keep cancer from spreading, however, and there is always the risk of bleeding in the digestive tract or the brain.
The authors conclude that there is impressive harmony between the biological action of aspirin and cancer outcomes in various studies. Nevertheless, they call for more research to verify their findings.
Other Aspirin Research:
Many other scientists have found that aspirin appears to have anti-cancer activity against a wide range of tumors. In a clinical trial of people who had been diagnosed with ovarian, prostate, lung or colorectal cancer, people taking aspirin at least three times a week were significantly less likely to die prematurely (JAMA Network Open, Dec. 2, 2019). The effect was strongest for colorectal cancer. However, benefits have also been found for prostate cancer (Cancer Treatment and Research Communications, Dec. 8, 2020) and pancreatic cancer (Journal of BUON, Sep-Oct. 2020).
People who use aspirin regularly appear to be diagnosed with lung cancer, leukemia, gastric cancer and esophageal cancer less frequently (Annals of Translational Medicine, Oct. 2020). A meta-analysis of 38 observational studies with nearly two million participants found that women who took aspirin were less likely to get breast cancer (Medicine, Sept. 18, 2020). This was especially true for “reducing the risk of hormone receptor positive tumors or in situ breast tumors” in postmenopausal women.
The Greatest Challenge of Treatment Is to Keep Cancer from Spreading:
As important as it is to reduce the risk of developing cancer, preventing its spread is just as critical. There are a number of studies that suggest aspirin can help in this process.
The authors of a systematic review concluded (PLOS One, April 20, 2016):
“It appears likely that low-dose aspirin has a beneficial role as an adjunct treatment of cancer. Reductions in mortality are shown in colon cancer, probably in prostate cancer and possibly in breast and individual studies of several other cancers also suggest benefit.”
The greatest fear of cancer survivors is that one day their cancer will return. For reasons that remain mysterious, sometimes seemingly successful treatments can eventually fail. That is to say, breast, prostate and many other cancers can recur 10 or 15 years after surgery, radiation or chemotherapy.
Seeking Prolonged Survival from Cancer:
Most current cancer treatment aims for prolonged survival, turning a malignancy into a chronic condition after the acute emergency has been overcome. Can surgery, chemo or radiation keep cancer from spreading and/or produce long-lasting survival? Sometimes they do, but not always.
Even the latest immunotherapy agents can’t guarantee a cure. Some of the hottest new drugs offer median “progression free-survival” of only several months. Translating from medicalese, that means about half the patients getting the treatment live longer than three or four months. In some cases, that is significantly longer than they would live without treatment. But it also means that about half the patients get less than three or four months.
A TV commercial for Opdivo (nivolumab) promoted the idea that this immunotherapy drug can provide some lung cancer patients “A Chance to Live Longer.” The message is that by taking this very expensive medication, patients “significantly increased the chance of living longer versus chemotherapy.”
What the commercial does not say, though, is that the average improvement in lifespan on Opdivo was about three months more than with chemo alone. The cost: roughly $6,580 per infusion, which is often every two weeks. Co-payments vary, of course, depending on insurance. In addition to the financial cost, side effects can be severe.
How Long Have We Known that Aspirin Could Keep Cancer from Spreading?
Although scientists published some of the studies cited above in 2020, researchers have long suggested that this old and inexpensive drug might have anti-cancer activity. In August, 1977, researchers writing in the Journal of the National Medical Association offered the following hypothesis that aspirin might keep cancer from spreading:
“Aspirin for Reducing Cancer Metastases?
“Distant metastases are the principal cause of death from cancer. Many animal experiments in the last 25 years have shown consistently that distant metastases can be significantly reduced by anticoagulants and fibrinolytic agents. Since aspirin inhibits platelet function and increases fibrinolytic activity in humans, it may be effective in preventing metastases in cancer patients. It is suggested that aspirin be offered as an option to cancer patients who are at risk for distant metastases.”
Oncologists are often quick to adopt the latest advances in cancer treatment. We understand their desire to extend the lives of their patients, even when the cost of the new drugs is prohibitive. What we do not understand, however, is their reluctance to consider aspirin as a potential addition to traditional treatment.
Adding Aspirin to Other Cancer Treatments:
Evidence indicates that when aspirin is used in combination with more conventional cancer treatments, it may improve survival. Scientists hypothesize that the anti-platelet properties of aspirin may help prevent tumor progression (Platelets, Dec. 2018). Platelets are the sticky part of blood that allow it to clot.
Investigators are currently studying whether aspirin can improve survival for people with prostate, breast, colorectal or gastro-esophageal cancer (The Lancet. Gastroenterology & Hepatology, Nov. 2019). Beyond those, some researchers are looking into possible benefits of adding aspirin to treatment for ovarian cancer (Women’s Health, Jan-Dec. 2020). They have also noted that aspirin may help prevent ovarian cancer in women whose risk is especially high.
Preventing Cancer with Aspirin:
So far, we’ve been discussing the possibility that taking aspirin could keep cancer from spreading. What about preventing cancer in the first place? There is a substantial amount of evidence that regular aspirin use can help people from developing colorectal cancer in the first place. A review in JAMA Oncology (March 3, 2016) notes that people taking aspirin were 19 percent less likely to develop this kind of malignancy.
The authors note:
“In two large prospective cohort studies, regular aspirin use was significantly associated with 3% lower risk of overall cancers, which was primarily due to a 15% lower risk of gastrointestinal cancers and 19% lower risk of cancers of the colon and rectum.”
To learn more about how aspirin might affect the risk of other cancers, here is a link.
It’s not all great news, though. A study presented at the American Society of Clinical Oncology (ASCO) in February, 2022 found that aspirin did not help prevent breast cancer recurrence.
What About Aspirin Side Effects?
Whenever anyone mentions aspirin’s potential benefits, some health professionals hoist their red flags and focus on the dangers. Aspirin, even in relatively small doses, is not benign. It can lead to stomach irritation and bleeding ulcers. The same risk holds for all NSAIDs, including diclofenac, ibuprofen and naproxen. Bleeding ulcers can be deadly.
Aspirin can also interact with many other drugs to increase the risk for hemorrhage. That’s why no one should ever undertake prolonged aspirin therapy without medical supervision. However, people should not overestimate the risk, either.
The PLOS ONE authors offer these intriguing insights about the harms:
“…in short-term trials the additional risk of a bleed from low-dose aspirin amounts to perhaps one or perhaps two patients in every 1,000 on low-dose aspirin. After about three years of aspirin taking however, there appears to be no evidence of any excess GI bleeds attributable to the drug…
“The most serious bleeds are those that lead to death, and despite frequent references to fatal bleeds attributed to aspirin, there appears to be no valid evidence that deaths from GI bleeds are increased by low-dose aspirin…
“Cerebral bleeds attributable to aspirin are rare, about one or two per 10,000 patient-years. Hypertension is the major factor in such bleeds and in a randomised trial of aspirin based upon patients with hypertensive disease all of whom were adequately treated with anti-hypertensive drugs, there was the same number of cerebral bleeds in ten thousand patients on aspirin (19 patients) as in ten thousand on placebo (20 patients).”
Regardless of the risk, no one should ever start taking aspirin on a regular basis without medical supervision. Aspirin can interact with many other drugs, including some used to treat cancer. As a result, oncologists must exercise careful oversight. People with cancer may want to ask their oncology team about using aspirin. They might inquire whether it would be safe or effective for their individual tumors. Because cancer treatment is so complex, aspirin will not be appropriate in many situations.
