New York—November 7, 2010
AIs, the standard adjuvant therapy for post-menopausal breast cancer, can cause joint pain in patients, mostly in the hands and wrists. This pain can sometimes be debilitating. “Patients complain bitterly about this pain that they can get in their hands after starting these medications,” said Lisa Mandl, M.D., an assistant attending rheumatologist at Hospital for Special Surgery in New York, who was involved with the study. “It is so bad that sometimes patients stop taking AIs, even though we know the drugs are literally life-saving—they decrease the risk of dying from breast cancer.” Studies have shown that up to 15% of patients on AIs discontinue their therapy due to pain.
Because few clinical trials have characterized this syndrome, investigators at Hospital for Special Surgery launched a prospective study to shed some light on the condition. “Nobody has really properly described this syndrome or tried to figure out what might predict you getting it,” said Dr. Mandl. “What is the pain? Is it joint arthritis? Is it tendonitis? Is it inflammation of the muscle? We wanted to describe it better than it has been described in the literature to date.”
The investigators enrolled 35 post-menopausal women with hormone-sensitive, non-metastatic breast cancer who didn’t have rheumatic disease. Subjects were evaluated at baseline, at three months, and at six months after starting aromatase inhibitor therapy. They underwent physical exams and filled out questionnaires about quality of life, health status and pain. Patients also underwent magnetic resonance imaging (MRI) scans at baseline, at the point they complained of any pain, and at six months.
“We were trying to detect inflammation and the anatomic location of their symptoms. Was the pain caused by inflammation in the joints or around the tendon, for example?” Dr. Mandl said.
The study classified women who reported new or worsening musculoskeletal symptoms as symptomatic. Of the 35 women enrolled, 19 (54%) were symptomatic and of these 2 (5.7%) discontinued AI therapy. The mean time to onset of symptoms was six weeks, range two to 18, and 58 percent of symptomatic subjects had pain in their hands. Roughly 11 percent had tenderness of tendons in their hand and 14 percent had generalized wrist stiffness.
The investigators found that MRIs were not always abnormal in symptomatic patients, although in some individual patients who experienced pain, doctors could detect abnormalities on their MRIs. There was no evidence of inflammatory arthritis on MRI, but some of the women who complained of pain had tenosynovitis, inflammation of the fluid-filled sheath that surrounds a tendon in the hand.
The investigators did not find any correlation between depression and pain. Other researchers have hypothesized that the syndrome might be caused by an autoimmune condition, but this study showed no association between autoimmune markers in the blood and pain. “I think it’s interesting that we didn’t find any autoimmune disease predisposition. We thought we might,” Dr. Mandl said.
Only one factor predicted whether women had pain—having later stage cancer. “If you have stage II or stage III cancer, you are more likely to have this pain than if you have stage I cancer,” Dr. Mandl said. She pointed out that women who had cancer that had metastasized to the bone were excluded from the study, so metastases were not the root of the problem.
“Before this study, we knew some women got this pain. Now we know that it is more likely in patients with later stage cancer and at least some of these women have tenosynovitis but not all,” Dr. Mandl said. “We were not able to identify any other predisposing factors.”
The lead investigator of the study was Ora Singer, M.D., who was at HSS during the study but is now a rheumatologist at the Medical College of Georgia Hospitals and Clinics. Other investigators involved with the study are Alana Levine, M.D., Tessa Cigler, M.D., Anne Moore, M.D., and Huong Do.
About HSS | Hospital for Special Surgery
HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the eighth consecutive year) and No. 3 in rheumatology by U.S. News & World Report (2017-2018). Founded in 1863, the Hospital has one of the lowest infection rates in the country and was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. The global standard total knee replacement was developed at HSS in 1969. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State. In 2017 HSS provided care to 135,000 patients and performed more than 32,000 surgical procedures. People from all 50 U.S. states and 80 countries travelled to receive care at HSS. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Global Innovation Institute was formed in 2016 to realize the potential of new drugs, therapeutics and devices. The culture of innovation is accelerating at HSS as 130 new idea submissions were made to the Global Innovation Institute in 2017 (almost 3x the submissions in 2015). The HSS Education Institute is the world’s leading provider of education on the topic on musculoskeletal health, with its online learning platform offering more than 600 courses to more than 21,000 medical professional members worldwide. Through HSS Global Ventures, the institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally.