Exercise Reduced Joint Pain From Breast Cancer Treatment

Patients who participated in an exercise program had clinically meaningful improvements in joint pain and stiffness.

As many as 20% of postmenopausal women on an aromatase inhibitor (AI) regimen for their hormone-positive breast cancer discontinue therapy within 12 months. There are also reports that up to 40% of patients are not taking their AI medication daily, according to Melinda L. Irwin, PhD, MPH, associate professor of epidemiology (chronic diseases) at the Yale School of Public Health in New Haven, Conn.

The most common reason for discontinuation is arthralgia (joint pain and stiffness), which as many as half of all women taking these agents experience within 6 months of starting treatment.

In the HOPE (Hormones and Physical Exercise) study presented by Dr. Irwin at the 36th annual 2013 San Antonio Breast Cancer Symposium (SABCS) held in San Antonio, Texas, women experiencing moderate joint pain who participated in an exercise program had clinically meaningful improvements in their AI-related arthralgia. The study is the first to test the effect of exercise for breast cancer survivors who are taking an AI.

The results also showed exercise helped led to a decrease in body weight and better cardiac fitness.

“Poor adherence and discontinuation have been independently associated with mortality,” said Irwin during a press briefing. “Exercise may be an especially attractive strategy to improve AI side effects, improve quality of life and perhaps adherence to AI, and overall survival.”

“The most important result here is that we can reduce some of the toxicities of treatment through relatively inexpensive interventions that are good for our general health also,” said Clifford Hudis, medical oncologist and chief of the breast cancer medicine service at Memorial Sloan-Kettering Cancer Center in New York, who was not involved in the study.

The HOPE trial randomized 121 women diagnosed with stage I–III breast cancer 1:1 to either an exercise program or no additional exercise program. Over 12 months, women in the exercise program arm took part in twice-weekly resistance training and 2.5 hours of moderate-intensity aerobic exercise per week. All women enrolled in the study were taking an AI for at least 6 months and reported a greater than 3 out of 10 on a joint pain scale.

The women in the exercise program increased their exercise to an average of 158.9 minutes per week of aerobic exercise compared with 48.9 minutes in the non-exercise group. Seventy percent of the 61 women in the exercise study arm attended the twice-weekly strength-training program. These women received a free gym membership and worked with a personal trainer.

After 12 months, women who exercised had 20% lower joint pain scores compared with 3% lower scores for women in the no exercise group (P = .017). Severity of pain also decreased significantly (P = .025) as did the amount the pain interfered with daily activities of the patients (P = .005).

“Those who were 80% or more adherent had a better improvement of joint pain,” said Irwin.

Body weight of those in the exercise group fell by an average of almost eight pounds compared with those in the no exercise group, who had a slight weight gain (P = .0057). Cardiorespiratory fitness also improved for those in the exercise program (P = .024).

Previous studies have shown exercise is beneficial for other patient populations, including those with rheumatoid arthritis, osteoarthritis, and fibromyalgia. Whether resistance training, aerobic exercise, or both lead to lower arthralgia is not clear from this study.

Women on the study were an average of 60 years of age, 2-years postdiagnosis, with mostly stage I or II disease. They were physically inactive and overweight.

AIs including letrozole, anastrozole, and exemestane are prescribed to breast cancer survivors who were diagnosed with postmenopausal estrogen receptor– positive breast cancer. Physicians generally recommend that patients take an AI for 5 years after initial breast cancer treatment to prevent recurrence.

Exemestane is also recommended for postmenopausal women at high-risk for developing hormone-positive breast cancer as a prevention mechanism. An additional study with anastrozole, the IBIS-II trial, also presented at SABCS, showed that this AI can decrease risk of developing breast cancer by 53%.

The mechanism by which exercise decreases arthralgia is not clear but could involve improvements in cardiac conditioning, strength and resistance to injury, and range of motion. The study researchers collected blood samples from patients that will be analyzed to understand whether system inflammation is decreased with longer-term exercise, which could contribute to symptom relief.

The study did not directly address whether exercise led to better adherence to daily AI regimen as only five patients discontinued their treatment. Dr. Irwin said she hopes the next study will directly address whether exercise and weight loss, in conjunction with starting an AI, will lead to better drug adherence.

“Clinical trials demonstrate that prolonged therapy [with AIs] is effective and advantageous,” said Dr. Hudis. “We don't know the full impact of noncompliance or early discontinuation [of this treatment], but it cannot be good. Overall discontinuation should be better understood, explored, and addressed.”

Dr. Hudis is part of a study at Sloan-Kettering exploring the role of obesity, energy balance, and cancer risk. “In many cases, clinicians already recommend careful diet and exercise, but what we need are even better tools to make sure the patients are able to comply with these recommendations,” he said.

The HOPE study was led by Dr. Irwin and Jennifer Ligibel, MD, of the Dana-Farber Cancer Institute in Boston, and was funded by the National Cancer Institute.