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Incidence of Carpal Tunnel Syndrome Higher Among Women Who Take Anastrozole Compared to Placebo

Mar 14, 2016

A study published in the Journal of Clinical Oncology (JCO) found that among postmenopausal women at risk for developing breast cancer, patients who took 1 milligram per day of the aromatase inhibitor anastrozole for 5 years had a significantly higher incidence of developing carpal tunnel syndrome (CTS), compared with women who took a placebo. CTS results from pressure on the median nerve, which runs from the forearm to the hand through a small space in the wrist called the carpal tunnel. The study, “Anastrozole–Induced Carpal Tunnel Syndrome: Results from the IBIS-II Prevention Trial,” was published online ahead of print, November 23rd.

Specifically, the study, which was based on data gathered from women in 18 countries across Europe, Australia, New Zealand, and South Asia, found that 65 (3.4%) out of the 3,864 women in the anastrozole arm developed CTS, compared with 31 (1.6%) out of the 1,944 women in the placebo arm. In addition, eight out of the ten cases reported as “severe” were among women in the anastrozole group, however this amounts to only 0.3% of the treatment population. The study also found that among the 24 women who reported surgical intervention for CTS, 18 were in the anastrozole group, however this amounts to 1% of the treatment population. The study also found that two other factors were independently associated with an increased risk of CTS, outside of treatment: high body mass index and other musculoskeletal symptoms.

The study’s first author, Francesco Spagnolo, MD, a researcher at Queen Mary University London, said the study is the first randomized, controlled study to assess risk factors and characteristics of CTS among women taking an aromatase inhibitor, compared to a placebo; previous trials looking at risk factors for CTS have compared aromatase inhibitors to tamoxifen.

More evidence that hormones may be at the root of carpal tunnel syndrome

The study’s findings about the connection between CTS and aromatase inhibitors—which stop the production of estrogen—are in line with the hypothesis that hormonal factors may play a role in the development of CTS. Studies show that women are three times more likely than men to develop CTS. In addition, pregnancy, surgical removal of both ovaries, and menopause—events which lower the amount of estrogen in the body—are associated with increased risk of CST, while menopausal hormone replacement therapy has been shown to help resolve CTS.

Knowing more about TCS risk may reduce non-adherence to anastrozole

According to Dr. Spagnolo, providing patients and clinicians more information about the risk and symptoms of CTS in the setting of aromatase inhibitors may improve adherence rates to the treatment—an important goal since aromatase inhibitors have become the established adjuvant treatment for postmenopausal women with hormone receptor-positive breast cancer.

“Studies show that as many as 25% of women stop taking aromatase inhibitors during the first year of treatment, and CTS, as well as other musculoskeletal syndrome may account for the non-adherence,” said Dr. Spagnolo. “But increased awareness of these adverse effects by patients and investigators may lead to a more precise reporting of symptoms. This would hopefully, in turn, lead to earlier diagnosis and better pain management that allows a patient to continue on treatment”.


Francesco Spagnolo, MD, has been a visiting doctor at the Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, in England. He is now a Researcher at IRCCS Azienda Ospedaliera Universitaria San Martino, in Genova, Italy. He has been an ASCO member since 2013.

Abstract of the original JCO article.

PDF of the original JCO article.

Spagnolo F, Sestak I, Howell A, et al. Anastrozole–induced carpal tunnel syndrome: results from the IBIS-II prevention trial. J Clin Oncol. Epub 2015 Nov 23. 


The Exclusive Coverage series on ASCO.org highlights selected research from JCO, JOP, and JGO, with additional perspective provided by the lead or corresponding author.

@ 2016 American Society of Clinical Oncology




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