Exercise Program Reduces Aromatase Inhibitor–Associated Joint Pain

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Melinda L. Irwin, PhD, MPH

Exercise, Joint Pain, and Aromatase Inhibitor Adherence

Jennifer A. Ligibel, MD

Our study showed that the better the adherence to exercise, the less joint pain the person experienced. The more research findings we have, the more likely clinicians will be to refer patients to exercise.

—Melinda L. Irwin, PhD, MPH

Amid studies of novel targeted therapies, genetic analyses of tumors, and new ways to approach the treatment of breast cancer, a low-tech study presented at the 2013 San Antonio Breast Cancer Symposium found that a yearlong exercise program reduced joint pain associated with aromatase inhibitors in breast cancer survivors.1 This is the first study to examine the impact of exercise vs usual care on the side effects of aromatase inhibitors.

The finding that exercise reduces joint pain could improve adherence to aromatase inhibitor therapy, improve quality of life, and reduce breast cancer recurrence and mortality risk, said the authors.

Poor Adherence Common

“[Aromatase inhibitors] are standard of care for hormone receptor–positive breast cancer, but numerous studies show that the side effects lead to poor adherence and drug discontinuation. Approximately 20% of women discontinue [aromatase inhibitors], and 40% don’t take the medications as prescribed. Arthralgias are reported in up to 50% of women within 6 months of starting [aromatase inhibitor] therapy,” said lead author Melinda L. Irwin, PhD, MPH, Associate Professor at the Yale School of Public Health and Co-Leader of Cancer Prevention and Control at the Yale Cancer Center, New Haven, Connecticut. “Many women report joint pain before starting an [aromatase inhibitor], and the pain gets worse [while they’re on the aromatase inhibitor],” she added.

“Our study showed that the better the adherence to exercise, the less joint pain the person experienced. The more research findings we have, the more likely clinicians will be to refer patients to exercise,” Dr. Irwin added.

“We’ve known for a long time that exercise is beneficial in breast cancer survivors, yet there aren’t many programs that patients can be referred to. Most medical oncologists haven’t focused on prescribing or recommending exercise, and the overall prevalence of exercise, especially strength-training, is low in breast cancer survivors,” stated co-author Jennifer A. Ligibel, MD, Assistant Professor of Medicine, Harvard Medical School and Dana-Farber Cancer Center.

Study Details

The HOPE study enrolled 121 women with stage I to IIIC hormone receptor–positive breast cancer who were taking aromatase inhibitors for an average of 1.5 years and experiencing at least mild arthralgias. Women were randomly assigned to a yearlong program of exercise or usual care. The exercise program, based upon the standard exercise recommendations from the U.S. Surgeon General, entailed twice-weekly supervised sessions that included six common strength-training exercises and 2.5 hours per week of moderate-intensity aerobic exercise. Patients assigned to usual care were provided with written information and physical activity recommendations and monitored with monthly phone calls to assess aromatase inhibitor adherence. Usual care patients were also offered a visit with an exercise trainer at the end of the study.

Pain was measured on the Brief Pain Inventory (BPI) scale of 0 to 10, where a score of 3 to 4 signified mild pain; 5 to 7, moderate pain; and 8 to 10, severe pain, with 10 signifying the most severe pain. Women entering the study had a mean BPI score of 6.

Women assigned to exercise were able to increase their exercise by about 110 minutes per week compared with the usual care group (P = .0001). Seventy percent of women assigned to the exercise program attended all of the twice-weekly strength-training sessions. Patients in the exercise program significantly increased their cardiorespiratory fitness (P = .0013) and reduced their body weight (P = .026) compared with those receiving usual care.

Over 12 months, patients assigned to exercise experienced a 30% decrease in worst pain, a 20% decrease in pain severity, and a 20% decrease in the amount of interference pain caused in daily activities, whereas those assigned to usual care experience about a 5% increase in these three parameters (P < .05 for all three comparisons).

Dose-Response Relationship

Morever, a dose-response relationship was seen with exercise. That is, the more adherent patients had more improvement in joint pain.

“Even some exercise improved outcomes,” Dr. Irwin pointed out. “Women assigned to exercise who only adhered some of the time experienced a 15% improvement in joint pain. Exercise makes activities easier to perform, and therefore people experience less pain,” she said.

“Exercise has the potential to improve [aromatase inhibitor] adherence and quality of life. Improvement in joint pain with exercise in this study has been shown to be better than with glucosamine, vitamin D, and acupuncture in other studies,” Dr. Irwin said.

The study was based on women who had free gym memberships, which made it easier for them to participate. Only five women dropped out of the exercise program. Dr. Irwin noted that there are a growing number of free exercise programs for cancer survivors, but these are typically available in larger cities and metropolitan areas. ■

Disclosure: Drs. Irwin and Ligibel reported no potential conflicts of interest.


1. Irwin ML, Cartmel B, Gross C, et al: Randomized trial of exercise vs usual care on aromatase inhibitor-associated arthralgias in women with breast cancer. 2013 San Antonio Breast Cancer Symposium. Abstract S3-03. Presented December 12, 2013.

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