Carpal tunnel syndrome and musculoskeletal symptoms in postmenopausal women with early breast cancer treated with exemestane or tamoxifen after 2-3 years of tamoxifen: a retrospective analysis of the Intergroup Exemestane Study

BACKGROUND: Aromatase inhibitors are more effective than is tamoxifen in prevention of breast-cancer recurrence, but at the expense of increased musculoskeletal side-effects, such as carpal tunnel syndrome. The aim of this study was to assess risk factors and the prognostic value of musculoskeletal symptoms during treatment with the steroidal aromatase inhibitor exemestane or with tamoxifen after 2-3 years of tamoxifen. METHODS: In the Intergroup Exemestane Study, postmenopausal women treated for early invasive breast cancer who remained disease free and on treatment after 2-3 years of tamoxifen were randomised to switch to exemestane or to continue tamoxifen for the remainder of the 5-year period of endocrine treatment. The primary endpoint for this retrospective analysis was occurrence of carpal tunnel syndrome and any musculoskeletal events, analysed in the safety population, which consisted of all patients who had received any trial treatment. As well as case-report forms, questionnaires were distributed retrospectively to gain more details of cases of carpal tunnel syndrome. The relation between musculoskeletal symptoms reported by 6 months from randomisation and survival from 9 months onwards was assessed by Cox proportional hazards models. The trial is registered, number ISRCTN11883920. It has completed accrual and follow-up is continuing for enrolled participants. FINDINGS: After a median follow-up of 91·0 months (IQR 83·0-99·2), carpal tunnel syndrome had been reported for 66 (2·8%) of 2319 patients in the exemestane group compared with 13 (0·6%) of 2338 in the tamoxifen group (odds ratio [OR] 5·23, 99% CI 2·39-11·49; p