With many types of medical treatments, patient face a tradeoff: They often endure pain or other side effects in exchange for drugs that control or cure a disease or condition. This holds true for some breast cancer patients using aromotase inhibitors.
Aromatase inhibitors are commonly prescribed to breast cancer patients who have hormonally-driven cancers and have already gone through menopause. These powerful drugs that go by the names Arimidex (anastrozole), Femara (letrozole) or Aromasin (exemestane), block the production of aromatase, an enzyme the body uses to generate estrogen. Breastcancer.org reports that by blocking this enzyme, “less estrogen is available to stimulate the growth of hormone-receptor-positive breast cancer cells.” Although aromatase inhibitors can’t stop the ovaries from making estrogen, in women who’ve gone through menopause or who are taking drugs to suppress ovarian function, AIs are effective in treating hormone-positive breast cancers.
These powerful drugs offer fewer side effects than most chemotherapy drugs, but as with virtually any form of treatment, they can cause some adverse effects. The most common, which impacts up to a third of patients, is joint pain and stiffness. Similar to how arthritis feels, this pain is temporary — it goes away when you go off the drug — but can be so significant that some patients will stop taking their AIs or alter their dosing schedule. And some don’t tell their doctors they’re skipping doses.
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“This is a huge problem and it negatively impacts cancer outcomes,” says Dr. Maryam Lustberg, associate professor of medicine and medical director of survivorship at the Stefanie Spielman Comprehensive Breast Center at the Ohio State University James Cancer Hospital. “We don’t blame the women, because it can be very painful and they may not be comfortable reporting to their physicians that they’re taking [their prescribed aromatase inhibitors only] three or four times a week,” instead of daily like they should, she says. But “there’s no data that reducing the dose that way makes it effective. So we caution against that.”
The joint pain these patients experience is apparently caused by an increase in inflammation that’s actually visible on MRI scans, Lustberg says, but the mechanism by which it occurs still isn’t fully understood. “Nobody really knows 100 percent,” says Dr. Dawn L. Hershman, leader of the Breast Cancer Program at the Herbert Irving Comprehensive Cancer Center at New York-Presbyterian/Columbia University Medical Center. “It comes from a lowering of estrogen. People who go through menopause also have increased joint symptoms, but we don’t really know what the mechanism is,” she says.
In searching for a solution, some researchers have turned to studies in patients with rheumatoid arthritis, a chronic inflammatory disorder in which the body’s own immune system attacks the joints. Omega-3 fatty acids — essential fats the body can’t make on its own but derive from fish, nuts and supplements — have been found to be effective in treating the pain of RA. Use of omega-3 supplements has helped some RA patients reduce their use of anti-inflammatory drugs to control symptoms. Because AIs are thought to be working on similar anti-inflammatory pathways, the idea emerged that perhaps omega-3 supplements could be helpful for joint pain caused by AIs.
In 2015, Hershman and her team published the first major study to look at the effect of Omega-3s on AI-induced joint pain. “Our trial included over 250 patients that were randomized to omega-3 fatty acids and placebo,” she explains. “We saw a large reduction in [symptoms] in the omega-3 fatty acid [supplemented group], but we also saw a large reduction in the placebo group.” After 24 weeks, patients in the omega-3 supplement group reported “a reduction in pain by a mean of over two points, which is clinically significant.” The placebo had a mean reduction of 1.8 points, which effectively amounts to “no difference between the two groups,” Hershman says. “They both resulted in patients having a lot of improvement in pain.”
So it seems the answer to the question of whether omega-3 supplements can help with this kind of pain is maybe, but maybe not any better than a placebo pill. Hershman says it could be that the placebo was active and that it actually reduced pain, or possibly that this sort of study simply offers the potential for a large placebo effect, a well documented phenomenon in which taking a placebo or non-effective drug alleviates symptoms despite the absence of an effective ingredient. If the dose of omega-3s had been different or the researchers had used a different placebo, perhaps the results would have been different.
“The reality is that from study to study, the placebo effect for [various interventions for aromatase inhibitor–induced joint pain] ranges from 0 to 50 percent. So it makes it challenging methodologically to study. But the results are the results,” and some patients in the trial experienced real reductions in pain. “In a pain study, maybe all that matters is that you get a meaningful reduction from the intervention. There are a lot of different ways of looking at it,” she says.
[See: Breast Pain? Stop Worrying About Cancer.]
Lustberg also recently concluded a small study that looked at this same question of whether omega-3s can alleviate AI-induced joint pain, but as a preventive measure rather than as an intervention after pain commenced. “Maybe omega-3s just aren’t strong enough to help” after symptoms start, she says, so the study looked at what would happen “if you take them at the onset of taking aromatase inhibitors to prevent the painful joint syndrome.”
Lustberg’s study offered mixed results. “In this small sample of 44 patients, some patients benefited and some did not. But when we put everybody together, it almost cancels out. There was not a significant difference, although there was some suggestion of benefit in certain quality of life measures.” She says the study showed that it’s feasible to take omega-3 supplements for prevention, and a larger ongoing study of more than 200 patients she’s currently conducting should provide more data about who is most likely to benefit from preventive omega-3 supplementation and how big an impact such measures could make. Lustberg says she’s also looking at genetic factors to see if she can’t better pinpoint which patients are most likely to experience this painful side effect.
Although Lustberg says the evidence doesn’t support the notion that everybody should take omega-3 supplements, she does note that they’re a “potent anti-inflammatory supplement.” More work needs to be done, but because omega-3 supplements are generally considered safe, if you’re having problems with joint pain, talk with your doctor about whether adding a supplement makes sense. Lustberg says patients in her study were given 4.3 grams per day of omega-3 supplements for 24 weeks and that dose was based on recommendations given to patients with rheumatoid arthritis. (Very high doses of omega-3 fatty acids have been linked to platelet disorders, increased bleeding risk or bruising more easily, so speak with your doctor about how to supplement safely.)
Although the jury is still out on the true benefits of omega-3 supplements to patients taking aromatase inhibitors, acupuncture may be an even better intervention. In a paper she presented at last month’s San Antonio Breast Cancer Symposium, Hershman found that when trial participants were randomized to either real acupuncture or sham acupuncture, those receiving the real acupuncture experienced a significant reduction in pain. “We did this large study looking at acupuncture because that’s something that is appealing to patients and doesn’t involve taking a medication or an intervention that has a lot of side effects,” she says. Finding a solution that’s palatable to patients and doesn’t cause additional side effects is key.
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To that end, exercise may be the best bet for reducing AI-induced joint pain. “Studies that have looked at exercise have shown the same two-point reduction on average in pain,” that her omega-3 study showed, Hershman says. Lustberg notes that “the more active people are, the more they’re at their ideal body weight and the more they reduce consumption of processed foods and processed sugar, they actually have less inflammation and fewer symptoms. Our culture really likes a pill and supplement, but in terms of lifestyle and intervention, exercise and diet really do help.”
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Can Omega-3 Acids Fight Joint Pain From Drugs to Treat Breast Cancer ? originally appeared on usnews.com
