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Background: Aromatase Inhibitor (AI) therapy is the most effective hormonal treatment in post-menopausal estrogen receptor (ER) positive breast cancer. Side effects such as arthralgias - termed aromatase inhibitor induced musculoskeletal syndrome (AIMSS) - limit their use in some patients. We evaluated factors associated with AIMSS and explored possible therapeutic options in a large cohort of patients. Methods: We performed an IRB-approved retrospective review of breast cancer patients seen in the Norris Cotton Cancer Center clinics from April 2011 to January 2013. 378 patients were included in our chart review on the basis of taking an AI for breast cancer with follow up documented in the electronic health record. Statistical analysis was performed by chi squared test for dichotomous variables and students t-test for continuous variables. Results: In our cohort 91% of patients were taking an AI as adjuvant therapy (9% for metastatic disease) with 41% (n=153) reporting new or worsening arthralgias after initiation of an AI. AIMSS was 42.5%(95%CI: 0.375 to 0.478) in the adjuvant and 22.7%(95%CI: 0.101 to 0.434) in the metastatic groups. The median time to symptom onset was 120 days. 2.1% (n=8) discontinued AI therapy due to AIMSS. There was no association with prior chemotherapy, baseline arthralgia, BMI, or statin use. We found an increased risk of developing AIMSS with more recent menopause (p=0.055), and therapy in the adjuvant setting (p=0.067). We also note a potential association of baseline osteoporosis and osteoporosis therapies with lower rates of AIMSS. Treatments included temporary discontinuation of AI, switching between AI, and non-steroidal anti-inflammatory therapy (NSAIDs). Of those attempting such treatment, all had improvement with temporary discontinuation, 25% improved after AI switch, and 85% had symptomatic benefit on NSAIDs. Conclusions: The incidence of AIMSS in our review was 41%. Patients treated in the metastatic setting may have a lower rate of AIMSS. Our cohort revealed that more recent menopause did seem to be a risk factor. Baseline osteoporosis and osteoporosis treatments have a potential association to be explored. Management options included switching between AIs, temporary discontinuation, and NSAID treatment. Updated analysis will be presented. Potential risk factors for the development of AIMSSCharacteristicN(-)Arthralgia N(%)(+)Arthralgia N(%)p-valueType of AI UsedAnastrozole204112(55.9)92(45.1)0.19Letrozole13183(63.4)48(36.6)Exemestane3623(64.9)13(36.1)Menopause timingLMP < 5 years prior to AI start15179(52.3)72(47.7)0.055LMP 5-10 years prior to AI start4023(57.5)17(42.5)LMP > 10 years prior to AI start155102(65.8)53(34.2)Type of therapyAdjuvant348200(57.5)148(42.5)0.067Metastatic2217(77.3)5(22.7)Baseline T-score by DEXA ScanNormal (T-score 0 to -1.49)11255(49.1)57(50.9)0.049Osteopenia (T-score -1.5 to -2.49)17196(56.1)75(43.9)Osteoporosis(T-score < -2.5)4029(72.5)11(27.5)On active osteoporosis therapy†(-) Therapy218118(54.1)100(45.9)0.03(+) Therapy12781(63.8)41(32.3)† Bisphosphonate/denosumab; LMP=Last menstrual period, AI=Aromatase Inhibitor, DEXA=Dual-energy x-ray absorptiomotry Citation Format: Clinton R Morgan, Zsolt Kulcsar, Jonathan D Jones, William F Rigby, Peter A Kaufman. Factors influencing aromatase inhibitor induced musculoskeletal syndrome: Roles of menopause timing and osteoporosis therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-12-09.