Abstract PS4-02-30 : Scoping Review of Biologic and Imaging Markers Associated with Aromatase Inhibitor Related Musculoskeletal Symptoms

Abstract Introduction: Aromatase inhibitors (AIs) are standard therapy for hormone receptor-positive breast cancer in postmenopausal women but are frequently associated with musculoskeletal symptoms (AIMSS) that impair quality of life and adherence. We summarize current evidence on biologic and imaging markers associated with AIMSS, to both clarify its underlying mechanisms and identify potential predictors, with the goal of guiding future strategies to improve AI adherence. Methods: We conducted a scoping review of original studies published between 2010 and 2025 that examined biologic and imaging markers for aromatase inhibitor related musculoskeletal symptoms in breast cancer patients, according to the PRISMA guidelines. Databases include PubMed, EMBASE, COCHRANE, JAMA, and Medline. Eligible studies reported on at least one of the following: breast cancer, aromatase inhibitors, arthralgia, biomarker, biological marker, inflammatory marker, imaging, radiology. Data were extracted in duplicate and synthesized narratively. Risk of bias was assessed using the ROBINS-I tool. Results: Thirteen studies met inclusion criteria. Participants were mainly postmenopausal women aged 50-67 with early-stage hormone receptor-positive breast cancer. Most studies evaluated markers after initiation of AI therapy, though a few included baseline assessments for comparison. Biomarkers included inflammatory markers (CRP, IL6, MCP-1), metabolic and lipidomic profiles (oxylipins, 8-HETE), hormonal markers (estradiol, sex binding protein), and genetic polymorphisms (CYP19A1, ESR1, HSD17B2). One study identified BMI as a clinical risk factor, and suggested IGF-1 as a potential biomarker, though it was not directly measured. Elevated inflammatory cytokines and lower estradiol levels were associated with AIMSS in several studies. Genetic findings were inconsistent, though newer studies identified novel variants like HSD17B2. Imaging assessments varied, with some studies performing baseline imaging and others focusing on early and serial imaging after AI initiation. Imaging methods included ultrasound, MRI, and shear wave elastography (SWE), with SWE showing promise as a quantifiable tool to detect early tendon stiffness. Discussion: Our review summarizes several markers that could be associated with in AIMSS, including inflammatory and hormonal pathways, genetic variants, and early imaging changes. However, these studies were limited by small sample sizes, heterogeneous methods, and have issues with reproducibility. While some markers show promise for predicting symptoms, the current evidence mainly advances understanding of AIMSS mechanisms. Future studies should integrate these markers to develop predictive tools, with the goal of improving AIMSS and AI adherence. Citation Format: S. RosenbergT. Escobar GilJ. Nemunaitis. Scoping Review of Biologic and Imaging Markers Associated with Aromatase Inhibitor Related Musculoskeletal Symptoms abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-02-30.