Abstract Background: Aromatase inhibitors (AI) are well known to be associated with troublesome musculoskeletal side effects but the underlying mechanisms are poorly understood and methods of objective assessment poorly defined. We have performed a prospective detailed evaluation of grip strength (primary endpoint), symptoms, imaging and biomarkers in patients receiving either an AI, tamoxifen or no endocrine therapy. Methods: 77 patients with early breast cancer from two specialist Breast Units were recruited prior to starting one of 4 treatment arms: upfront AI (A), switch from tamoxifen to AI (B), tamoxifen (C) and no treatment (D). Arthralgia was defined as worsening of joint pain score at 3 months and a positive Tinel's or Phalen's test was taken as evidence of carpal tunnel syndrome. Grip strength was measured (average of three readings from each hand) using a Jamar Dynamometer at baseline, 1, 2, 3, 6 and 12 months. In addition, biochemical (endocrine and collagen markers), rheumatological (inflammatory and cytokine markers) and radiological assessments of the hands (diagnostic ultrasound, bone density using DXA and plain radiograph) were performed at protocol-specified intervals. A subset of patients also underwent hand MRI at baseline, 3 and 12 months. Detailed rheumatological examination and questionnaire (DAS-28, SF-36, HAQ-DI and BPI-SF) assessment were performed at each visit. Grip strength was analysed using analysis of covariance with age, prior chemotherapy and baseline grip as covariates. The Kruskal-Wallis test was used for questionnaire data. The 3 month data on grip strength, questionnaire, clinical assessment and hand ultrasound are presented here. Results: 47 patients received an AI (34 upfront, 13 switch), 22 tamoxifen and 8 no endocrine treatment (controls). Median age (yearrs) for each group was: 62.1 (A), 51.0 (B), 65.2 (C) and 61.2 (D). The incidence of arthralgia at 3 months was 38% (A), 17% (B), 38% (C) and 14% (D). Mean baseline grip strength was similar in each arm: 22.5kg (A), 23.1kg (B), 20.2kg (C) and 23.2kg (D) (p=0.342 ANOVA). At 3 months, the mean percentage change in grip strength was +0.2% (A), +2.2% (B), +4.5% (C),+1.2% (D) (p=ns ANCOVA). In those on AI, the development of arthralgia was not shown to be associated with change in grip strength (p=0.82). Morning stiffness was also no different at 3 months. Clinical signs of carpal tunnel syndrome were evident in 10/45 (22%) of patients receiving AI therapy compared to 4/28 (14%) on tamoxifen/control. There were 4 cases of trigger thumb or finger, all in patients receiving AI treatment. Changes in HAQ-DI and pain (VAS) at 3 months were no different between groups (p=0.27, p=0.1 respectively). Ultrasound assessment of the flexor tendons at 3 month identified an increase in median score for tendon sheath fluid in those in the AI groups (3 (AI) v 1 (No AI) p=0.07, Mann-Whitney U test). There was no significant change in average median nerve cross-sectional area at 3 month. Conclusion: This study suggests that patient reported arthalgia does not correlate with early changes in and mean grip strength. However, there may be early signs of carpal tunnel syndrome, trigger finger and fluid in the flexor tendon sheaths detectable by ultrasound. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-18.