Newsletter #82–Jul./Aug. 2004
Beyond Headaches: Aspirin Associated with Lower Breast Cancer Risk
by Jane Sprague Zones
Years ago, researchers noticed that arthritis patients were less likely than others to develop cancer, and they began to look at the effects of aspirin for applications other than pain relief. Retrospective studies1 of aspirin have suggested that it reduces the likelihood of developing breast cancer. Dr. Samuel Epstein, the Michael Moore of cancer politics, has been intimating for years that aspirin may be a low-cost, safer alternative to tamoxifen and other expensive therapies that are being promoted to lower breast cancer risk.2
A report published recently in the Journal of the American Medical Association (JAMA),3 by Mary Beth Terry and associates, adds further understanding of this relationship. Terry, et al., compared 1,442 women with breast cancer with 1,420 healthy women and found that those without breast cancer were more likely to be regular users of aspirin and that the effect was greater for frequent users (seven or more tablets weekly). How often a woman took the drug was more important than the length of time she had taken it.
The unique contribution of the Terry study is that it showed the particular effectiveness of aspirin in reducing the risk of hormone-receptor positive breast cancer (that is, breast cancer that is sensitive to hormones, which accounts for about two-thirds of breast cancers). They found that aspirin use was associated with a 20 percent reduction in breast cancer risk in this group.
The Terry study analyzed the effects of ingesting all kinds of over-the-counter pain relievers (called analgesics) on breast cancer risk. There are two kinds of analgesics: nonsteroidal anti-inflammatory drugs (NSAIDs), which include aspirin and ibuprofen; and acetaminophen, such as Anacin and Tylenol. Aspirin and other NSAIDs block two enzymes, cox-1 and cox-2.4 Cox-2 promotes cell growth and the development of blood vessels in tumors, and it is involved in increased estrogen production in breast tissue. Cox-1 protects the lining of the stomach, initiates blood clotting, and regulates blood flow to the kidneys.
Acetaminophen diminishes pain and fever in a different way, raising the pain threshold in the central nervous system. Terry, et al., found that only NSAIDs, and not acetaminophen, were associated with a reduction in breast cancer risk. Results with aspirin were stronger than with other NSAIDs, possibly because a substantially greater number of women in the sample used aspirin and those results therefore had greater statistical strength.
Because NSAIDs inhibit the cox-1 enzyme as well as cox-2, they have significant side effects, including stomach inflammation and ulcers, intestinal bleeding and, rarely, hemorrhagic stroke (bleeding in the brain). Overuse is associated with dizziness, high blood pressure, ringing in the ears, and kidney and liver difficulties. Most of these side effects are not common, and they are reversed when the drug is no longer taken.
A new class of arthritis painkillers, called cox-2 inhibitors (the main ones are Celebrex, made by Pharmacia, and Vioxx, made by Merck) would presumably provide the benefits of the NSAIDs without many of the harmful side effects, since they do not block the cox-1 enzyme. These drug companies are conducting studies to see the effects of cox-2 inhibitors on cancer risk, and anticipate overseeing a huge expansion in their market. The cox-2 inhibitors are very expensive and require a physician’s prescription.
Although “regimen” aspirin (low-dose aspirin that many older people take daily to allay heart conditions—81 mg compared with 325 mg in a regular adult aspirin) are easily available over the counter, are much less expensive than comparable prescription medications, and have been used relatively safely for many years, the medical community is approaching the widespread use of aspirin to lower the risk of breast cancer with great caution.
The authors of the JAMA article noted that they did not ask subjects about dosages and that further research would be required to substantiate their findings and to find the safest and most effective treatment regimens. They wisely recommended a randomized prospective trial5 that would follow women for a long period to see aspirin’s effects compared with those of a placebo. This is the only way to establish the causal effects on breast cancer risk.
Most drug research, even that conducted in academic medical centers, is sponsored by pharmaceutical companies these days. They have little interest in furthering our understanding of aspirin’s benefits, because there is no patent ownership and little profit to be made. The study by Terry, et al., was piggybacked on a much larger research project looking at environmental links to breast cancer incidence, the Long Island Breast Cancer Study Project, which was sponsored in large part by the National Cancer Institute (NCI) and the National Institute of Environmental Health Sciences.
Press reports and a recent poll of doctors on the Internet site Medscape indicate that most physicians are adopting a “wait and see” attitude toward recommending regular aspirin use to their female patients who are at risk for breast cancer. This is in contrast to the general enthusiasm in the medical community toward prescribing drugs such as tamoxifen and the new aromatase inhibitors to lower breast cancer risk in healthy women. These drugs, still under patent protection and with a relatively brief track record, are extremely expensive and have much more damaging side effects than aspirin and the other NSAIDs. Much of the enthusiasm for them is driven by pharmaceutical company promotions to physicians and to potential users through direct-to-consumer advertising.
Women need to lobby the NCI to encourage randomized controlled trials of aspirin’s effects on breast cancer risk, so that we can better understand its benefits and liabilities, with the potential to have an inexpensive, relatively safe, and easily available alternative for women seeking to lower their chances of developing breast cancer.
TAKE ACTION: Tell the NCI what you think. Contact NCI Director Andrew von Eschenbach at avonesch@mail.nih.gov or 301/496-5615. If you’re concerned about the practice of using pills for prevention, visit the Prevention First web site.
1 A retrospective is study an observational study in which data is drawn from recollection or records of past behavior.
2 Samuel S. Epstein, The Politics of Cancer Revisited, East Ridge Press, Freemont Center, NY, 1998, p. 490.
3 Mary Beth Terry, Marilie D. Gammon, Fang Fang Zhang, et al., “Association of Frequency and Duration of Aspirin Use and Hormone Receptor Status With Breast Cancer Risk,” JAMA 291 (No. 20); May 26, 2004, 2433–2440.
4 Cox is an abbreviation for cyclooxygenase.
5 A prospective study is a study in which subjects are followed from a given point in time into the future.