Rheumatologic Evaluation of Adjuvant Letrozole in Post-Menopausal Breast Cancer Patients Discontinuing Anastrozole Due to Grade 2-3 Arthralgia – Myalgia.
Authors: Yardley D. , Green N. , Papish S. , Lake S. , Culver K. , Argonza-Aviles E. , Warsi G. , Hart L. 
Published: December 2010

Abstract
Background:Non-steroidal aromatase inhibitors (AIs) are standard of care in the adjuvant treatment of postmenopausal women with hormone receptor positive (HR+) early stage breast cancer. Side effects such as arthralgia and/or myalgia (A/M) occur in 20 -35% of women on AI therapy with onset as early as 1-2 months from AI initiation. As many as 20% of patients may discontinue therapy due to A/M. Switching to another AI could improve the A/M and allow patients to remain on AI therapy. This study evaluated if patients (pts) who discontinued anastrozole (Ana) due to grade 2-3 A/M would be able to continue AI therapy if switched to Let. We measured whether switching to Let resulted in a lower proportion of grade &gt;2 A/M symptoms and less discontinuation among women who previously discontinued Ana therapy due to A/M.Methods: Pts were eligible for treatment with Let (2.5mg/day for 6 months) if they were postmenopausal, HR+, had early stage breast cancer including LCIS and DCIS, and experienced grade 2-3 A/M on Ana resulting in discontinuation. Pts taking analgesics for any reason were excluded. A/M symptoms and self reported quality of life (QoL) outcomes were assessed by Basic Pain Inventory (BPI), Visual Analog Scale (VAS) and Health Assessment Questionnaires (HAQ) at baseline, during Let therapy and upon study completion. Pts tolerating Let therapy at 6 months had the option of continuing Let for their prescribed course of 5 years.Results: The study enrolled 261 pts of which 2 pts were ineligible. The median age of pts was 61, and 235 (90%) were Caucasian, 14 (5.4%) were Black, 3 (1.2 %) were Asian and 9 (3.4%) were other. At baseline, 107 (41.0%) and 70 (26.8%) had grade 2 or higher A/M respectively. At study completion, fewer patients suffered from grade ≥ 2 A/M, 61 (23.6%) and 46 (17.8%) respectively. Changes in QOL assessments showed a statistically significant improvement (p &lt;0.05) according to the BPI composite score, VAS scale and disability index of the HAQ at -0.5, -6.4 and -0.1 respectively. 228 (87.4 %) pts remained on Let therapy until study completion (6 months). Only 25 (9.6%) of the 261 pts enrolled discontinued due to A/M and another 8 (3.1%) discontinued for other reasons. The mean time to AI discontinuation due to A/M was 157 days and the median duration of study drug was 169 days. Baseline A/M grade, age, BMI, prior use of pain medications or baseline vitamin D results were not significantly associated with Let discontinuation.Conclusion:These results suggest that pts who are intolerant of and have discontinued Ana due to A/M may better tolerate AI therapy and avoid discontinuation when switched to Let. Less A/M and QoL function were maintained upon switching to Let with, 228 (87.4 %) of women in this study remaining on therapy with Let despite previous discontinuation of Ana due to A/M.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 805.