Recent studies have concluded that aromatase inhibitors are the most effective adjuvant anti-hormone therapy for post-menopausal women with estrogen receptor positive breast cancer [1]. Unfortunately about 50% of these women who are treated with aromatase inhibitors complain of significant joint pain which has been termed aromatase inhibitor-induced arthralgia (AIA) syndrome [2-4]. The pain can be so bothersome that 13-22% will stop the aromatase inhibitors before the five-year recommended time [4, 5].

There has not been found an ideal therapy other than stopping the aromatase treatment. Unfortunately stopping treatment may preclude the best outcome for preventing recurrence of breast cancer or new lesions in the other breast. Occasionally switching to another aromatase inhibitor may be helpful [6]. Reported, herein, may be a new treatment option for AIA, treatment with dextroamphetamine sulfate.

A 53-year-old woman developed Stage I breast cancer and was treated with a mastectomy. She was subsequently treated with letrozole 2.5 mg daily. After 15 months she developed severe right shoulder pain. Following an evaluation with an orthopedic specialist, no organic cause was determined by testing. She was diagnosed with a frozen shoulder syndrome.

She proceeded with physical therapy, but not only did she not improve, but the pain spread to her left shoulder. The pain was worse at night and would keep her from sleeping most of the night. Non-steroidal anti-inflammatory drugs did not relieve the pain. This woman had been treated for 25 years for unexplained thigh pain and edema which was exacerbated by running. This was completely relieved by treating with dextroamphetamine sulfate which has been very effective for many other pain syndromes and has been called the sympathetic neural hyperalgesia edema syndrome [7-9]. In fact, she had been on 30 mg extended release capsules when the arthralgia began. A decision was made to increase the dosage of dextroamphetamine sulfate to 45 mg per day. Within three weeks the pain diminished to the point that she has been able to sleep during the night. The pain is still present but much better and is reduced sufficiently to allow her to function normally. In fact she does not need to even take aspirin or other non-steroidal inflammatory drugs but sometimes uses a heating pad.

Sympathomimetic amine therapy has been successful in treating previously intractable pain syndromes involving the musculoskeletal system [7-11]. The median time of treatment with aromatase inhibitors and the AIA syndrome is 1.6 years, similar to this patient who is reported herein [4]. One cannot state with certainty that the pain was caused by the letrozole since it has been suggested that to demonstrate the existence of AIA, one should demonstrate abatement of symptoms after stopping aromatase drugs and return of symptoms when resuming, and this was not done for this patient.

The marked improvement of pain persisted for 12 months and is enabling her to remain on aromatase therapy hopefully for the five years that is planned. At the 2014 American Association for Cancer Research, Nirwvath et al., presented the theoretical basis for prescribing high dosage vitamin D to help the AIA syndrome. They are approved for a randomized controlled study of 184 women, half of which will receive high dosage vitamin D (50, 000 IU vitamin D) three times per week for 12 weeks, followed by 2, 000 IU vitamin D for 40 weeks, whereas the controls will receive standard dose vitamin D3 of 800 IU vitamin D3 daily for 52 weeks [12]. High-dosage vitamin D3 has several potential side effects. In contrast dextroamphetamine sulfate is very well tolerated and in the dosages used can be stopped abruptly without withdrawal symptoms and drug dependence does not occur in the usual prescribed dosages [7]. One does not usually develop resistance to this treatment over time. Thus, it is hoped that this case report can stimulate a trial of dextroamphetamine sulfate for AIA especially if the high dose vitamin D trial does not prove very effective [12].