Prospective characterization of musculoskeletal symptoms in early stage breast cancer patients treated with aromatase inhibitors
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Purpose Aromatase inhibitors (AIs) are increasingly used as adjuvant treatment of postmenopausal women with hormone receptor-positive breast cancer. AIs are commonly associated with musculoskeletal symptoms. The primary objective of this study was to describe the musculoskeletal symptoms that developed in the first 100 subjects enrolled who had at least 6 months follow-up. Methods Women with early stage hormone receptor-positive breast cancer were recruited into a multicenter randomized clinical trial to study the pharmacogenomics of two AIs, exemestane, and letrozole. Patients completed the Health Assessment Questionnaire (HAQ) and Visual Analog Scale (VAS) at baseline, 1, 3, 6, and 12 months to assess changes in function and pain, respectively. Patients were referred for evaluation by a rheumatologist if their HAQ and/or VAS scores exceeded a predefined threshold. Results Forty-four of 97 eligible patients (45.4%) met criteria for rheumatologic referral. Three patients were ineligible because of elevated baseline HAQ (2) and failure to initiate AI therapy (1). No baseline characteristics were significantly associated with referral. Median time to onset of symptoms was 1.6 months (range 0.4–10 months). Clinical and laboratory evaluation of patients evaluated by rheumatology suggested that the majority developed either non-inflammatory musculoskeletal symptoms or inflammation localized to tenosynovial structures. Thirteen patients discontinued AI therapy because of musculoskeletal toxicity after a median 6.1 months (range 2.2–13 months). Conclusions Musculoskeletal side effects were common in AI-treated patients, resulting in therapy discontinuation in more than 10% of patients. There are no identifiable pre-therapy indicators of risk, and the etiology remains elusive.
KeywordsAromatase inhibitor Arthralgia Breast cancer Musculoskeletal symptoms Rheumatology
Supported in part by: Pharmacogenetics Research Network Grant Number U-01 GM61373 (DAF) and Clinical Pharmacology training grants 5T32-GM08425 (DAF) from the National Institute of General Medical Sciences, National Institutes of Health, Bethesda, MD. Grant Numbers M01-RR000042 (UM), M01-RR00750 (IU), and M01-RR00052 (JHU) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. Grants from Pfizer, Inc. (DFH), Novartis Pharma AG (DFH), and Fashion Footwear Association of New York/QVC Presents Shoes on Sale™ (DFH) ClinicalTrials.gov number: NCT00228956.
Disclaimers: Consultant—LabCorp (DAF), Roche Molecular Diagnostics (DAF), Wyeth (VS), Pfizer (DFH), Honoraria—Pfizer (AMS), Pfizer (DFH), Research Funding—Pfizer (DAF, DFH, VS, DA, AMS), Novartis (DAF, DFH, VS, DA), AstraZeneca (DAF), GlaxoSmithKline (VS)
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