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Aromatase Inhibitors, Treatment-related Pain and What Patients Can Do

contributed by Shelley Zalewski

Woman sitting on couch rubbing her wrist

Aromatase inhibitors are a game-changer for the treatment of some breast cancers, but many patients experience muscle and joint pain. A Rogel Cancer Center specialist discusses what’s behind treatment-related pain and what patients can do about it.

What if there was a drug that cut the risk of breast cancer returning in half, but it came with severe muscle and joint pain? That’s the dilemma facing some women with breast cancer. But a University of Michigan Rogel Cancer Center oncologist says it doesn’t need to be a choice between breast cancer and living in pain.

More than half of all breast cancers are driven by the hormone estrogen, which makes them ideal candidates for treatment with a class of drugs called aromatase inhibitors, or AIs. These are prescribed for post-menopausal women after surgery and are taken for a period of five to 10 years. AIs stop the body from producing estrogen. This approach has proven effective, reducing the chance of breast cancer coming back by about half.

As with most cancer medications, taking AIs poses a risk of side effects. The most common is pain – specifically joint pain, joint stiffness and muscle aches, usually in the hands, feet, ankles and knees. Roughly half of women experience some musculoskeletal pain while taking AIs. In most cases, the pain is bothersome but manageable. But for about one in five of those women, the pain is severe and persistent enough that they consider switching to a different medication or even stopping the therapy entirely.

“Patients tell me the pain makes them feel as though they have suddenly grown very old,” says N. Lynn Henry, M.D., Ph.D., breast oncology disease lead at the Rogel Cancer Center. “Some women experience stiffness and pain when first rising in the morning, or after sitting for a period of time, and it lessens once they move around. For others, the pain is awful, sapping their energy and focus and making it hard to do even basic tasks.”

For Henry, a medical oncologist, addressing treatment-related pain is a major goal in the clinic, and a primary focus of her research.

“Stopping an AI drug too soon can increase the risk of cancer coming back,” she explains. “We need to do all we can to understand the link between these medications and pain symptoms, to help prevent or reduce pain and make it easier to stay on this life-saving therapy.”

Making Sense of the Pain

It’s not clear why some women develop pain while taking AIs. Henry and her fellow researchers believe it may be the result of increased inflammation in the body stemming from very low estrogen levels.

One current study takes a page from recent science about a different cause of inflammation: eating an unhealthy diet. The typical American diet tends to contain high levels of inflammation-causing fat particles. To counteract the inflammatory fats in the foods we eat, some health professionals recommend taking dietary supplements derived from fish, called omega-3 fatty acids.

“In some women, we think that taking an AI drug may drive inflammation and pain,” Henry explains. Her team is looking at whether taking omega-3 fatty acid pills can help women build levels of anti-inflammatory fats women build levels of anti-inflammatory fats to fight AI-related pain.

Henry’s research is funded in part by a Robin Roberts Thrivership translational grant from the V Foundation.

Other Pain-Fighting Strategies

For women experiencing pain from AIs, Henry advises either participating in a clinical trial or trying one of these other promising approaches to manage their pain.


“It’s always wise to start by exploring non-pharmaceutical options to manage pain,” she says. “We encourage patients to exercise and stay active to improve their general health. Many find that movement helps them work through some AI-related stiffness and pain.”


“We have evidence from a large-scale randomized clinical trial that shows that acupuncture can help reduce AI-related pain,” notes Henry. Another study suggested acupressure could be a low-cost, at-home solution to a host of breast cancer side effects, including pain.

Over-the-counter anti-inflammatory medications

Some patients get moderate pain relief by taking medicines that reduce inflammation such as ibuprofen and naproxen. “But it’s important to keep in mind that these target different kinds of inflammation in the body than omega-3 fatty acids,” Henry cautions. “They tend to not work that well for this type of pain in many women. And taken too often, they can increase the risk of damage to the liver and kidneys.”


Duloxetine, marketed under the trade name Cymbalta, is a medication used to treat depression. It seems to work by changing the interplay of two chemicals in the brain: serotonin and norepinephrine. These chemicals regulate several brain functions, including the way we recognize and feel pain.

Duloxetine was approved by the Food and Drug Administration in 2004 to treat not only depression, but some types of chronic pain, including fibromyalgia, knee arthritis and lower back pain.

In 2017, a landmark study by the national cancer research consortium SWOG demonstrated that duloxetine was also an effective treatment for joint pain and stiffness in women with early-stage, hormone-receptor-positive breast cancer who were taking AIs after surgery.

“We know that more than half of the women studied who took duloxetine experienced a reduction in their pain,” says Henry, who was part of the research. “But we’re not sure why those particular women got relief. Follow up research is underway testing the levels of inflammation in the blood before and after taking the medication to learn more.”

The Bottom Line: Give Voice to Your Pain

Henry’s advice to breast cancer patients experiencing pain while taking AIs: Don’t suffer in silence, and don’t stop taking your medication.

“No woman should have to endure pain that limits mobility or quality of life,” she says. “And no woman should ever have to choose between survival and relieving pain. Talk to your doctor if pain, or any other side effect, is making it difficult to tolerate your aromatase inhibitor. There are options you can pursue together to help you stay on this life-saving treatment.”

Learn more about breast cancer, treatment side effects and aromatase inhibitors

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