This patient should be started on tamoxifen. She has aggressive stage IIIA breast cancer with four positive axillary lymph nodes. With adjuvant chemotherapy alone, she remains at high risk for recurrence and should receive at least 5 years of antiestrogen therapy, ideally with at least 2 years of an aromatase inhibitor, if tolerated. A recent study has demonstrated that extending aromatase inhibitor therapy to 10 years may further reduce the incidence of recurrence. As aromatase inhibitors may be associated with debilitating musculoskeletal symptoms, such as arthralgia in this patient, these agents should be discontinued if patients cannot tolerate them and tamoxifen should be started as an alternative antiestrogen therapy.

Approximately one third of patients taking aromatase inhibitors develop intolerable adverse effects that lead to discontinuation of these agents. In one study, 22% of all patients stopped taking these drugs following development of the aromatase inhibitor–induced arthralgia syndrome (AIIAS). Predictors of AIIAS include younger age, prior taxane chemotherapy, and a history of pre-existing joint pain. The cause of the musculoskeletal symptoms, which can occur in the upper or lower extremities, is unknown. This patient's symptoms of joint pain that are symmetric, bilateral, and worse when lying down or sitting are very typical of AIIAS.

Her symptoms are not concerning for metastases, especially because the arthralgia resolved when aromatase inhibitors were discontinued. Therefore, a PET scan is not indicated at this time.

For patients whose aromatase inhibitor–induced arthralgia does not respond to NSAIDs, treatment with duloxetine has been of benefit in clinical trials and is under further study. There is no known benefit to using prednisone for AIIAS. The Hormones and Physical Exercise (HOPE) trial showed that a regular exercise program can ameliorate arthralgia caused by aromatase inhibitors.

Restarting anastrozole will almost certainly cause the same intolerable arthralgia and is therefore not indicated. In one prospective trial of patients with AIIAS, stopping the initial aromatase inhibitor for 2 to 8 weeks and then switching to an alternate aromatase inhibitor resulted in 40% of patients being able to continue with the alternate agent. No studies to date support recommending a third attempt at use of aromatase inhibitor therapy.