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#1142 Background: Aromatase inhibitors (AIs) are standard adjuvant therapy in postmenopausal women (PMW) with hormone receptor-positive breast cancer (HR+BC). The estrogen-deficient environment induced by AIs may predispose women to increased bone loss and arthralgia. Switching from one AI to another has been shown to improve arthralgia. However, clinical trial data documenting the course of joint pain symptoms in switching studies has been sparse. The Articular Tolerance of Letrozole (ATOLL) study evaluates the tolerability of letrozole (L) in patients who were switched from anastrozole (A) due to severe joint pain.
 Objectives: This study included PMW with HR+BC who experienced severe joint pain with A requiring discontinuation and then switched to L. The aim of the study was to (i) determine the incidence of L discontinuation due to joint pain (ii) identify predictive factors for L tolerance.
 Methods: Only PMW with HR+ BCwho experienced severe joint pain on A requiring discontinuation were eligible for this 6-month prospective open-label, multi-centre trial. Treatment with L was initiated following a 1 month washout period. Pain assessment was done by a oncologist just prior to L initiation and after six months of follow up. Outcomes were based on patient reports of joint pain after initiating L. A central review was done by a rheumatologist. Statistical evaluations were determined on a 95% CI, and correlations were performed using a Cox model.
 Results: 179 PMW with HR+ breast cancer (mean age 61.3 ± 8.4) were eligible. The mean duration of A treatment prior to discontinuation was 14.6 ± 10.59 months with 126 (73.7%) on A for more than 6 months. At the end of the 6 month follow-up, 128 patients (71.5%) remained on L and continued by choice while 51(28.5%) patients discontinued L due to worsening of joint pain;73.5% patients discontinued due to arthralgia and 21% due to muscle pain . Hands, knees and spine were the most commonly affected joints. There was no association between L discontinuation with age, duration of menopause, socio-demographic status or previous joint disorders including osteoarthritis. The predictor of L discontinuation was significant only for the duration of the previous A treatment (p=0.04).
 Conclusion: These data suggest switching from anastrozole to letrozole may help to maintain the benefit of AI therapy in patients who complain with severe joint pain and support the reported findings of Renshaw et al that more than 50% of women obtained relief of joint pain by switching from one AI to another. Symptomatic arthralgia due to prolonged use of A reduced the usefulness of switching to L in this patient cohort, therefore, switching from one AI to the other at the onset of symptoms may help to maintain the benefit of AI therapy in patients who complain of severe joint pain. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1142.

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