Scoping review of biologic and imaging markers associated with aromatase inhibitor related musculoskeletal symptoms
- 1Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA
- 2Department of Hematology and Oncology, University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico, USA
Abstract
Background: Aromatase inhibitors (AIs) are standard adjuvant therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer, yet up to half experience aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) that reduce quality of life and compromise adherence. We aim to better understand the biologic and imaging factors involved in AIMSS, which may improve early identification and management of these toxicities.
Methods: We conducted a scoping review of studies published between 2010 and 2025 examining the biologic and imaging markers associated with AIMSS in breast cancer patients. We followed PRISMA-ScR guidelines and searched PubMed, EMBASE, Cochrane, JAMA and MEDLINE for original studies assessing biomarkers or imaging modalities linked to AIMSS. Our search terms included: breast cancer, aromatase inhibitors, arthralgia, biomarkers, biological marker, inflammatory marker, imaging, radiology. Thirteen studies met inclusion criteria, with predominantly postmenopausal women aged 50–67 years with early-stage HR+ disease. Biomarker categories included inflammatory cytokines [C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1)], metabolic and lipidomic profile [oxylipins, 8-hydroxyeicosatetraenoic acid (8-HETE)], hormonal markers (estradiol, sex hormone-binding globulin) and genetic polymorphisms (CYP19A1, ESR1, HSD17B2).
Results: Elevated inflammatory and metabolic markers and lower estradiol levels on AI treatment were associated with AIMSS in several studies, while genetic associations were inconsistent, though newer work identified variants such as HSD17B2. Imaging approaches included ultrasound, magnetic resonance imaging (MRI), and shear wave elastography (SWE), with early and serial imaging showing potential for detecting tendon or soft tissue changes preceding symptoms. SWE may be a quantifiable tool for identifying early biomechanical changes. One study highlighted body mass index (BMI) as a potential clinical factor and proposed insulin-like growth factor as an unmeasured biomarker candidate.
Conclusions: Overall, inflammatory and hormonal pathways, novel genetic variants, and early imaging changes represent promising approaches for understanding AIMSS. Larger, standardized studies that integrate these biologic and imaging data are needed to improve risk prediction and support adherence to endocrine therapy.
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BibTeX
@article{rosenberg2026scoping,
title = {{Scoping review of biologic and imaging markers associated with aromatase inhibitor related musculoskeletal symptoms}},
author = {Stephanie Rosenberg and Tomas Escobar Gil and Jacklyn Nemunaitis},
journal = {Translational Breast Cancer Research},
year = {2026},
month = may,
doi = {10.21037/tbcr-2026-1-0004},
url = {https://doi.org/10.21037/tbcr-2026-1-0004},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Scoping review of biologic and imaging markers associated with aromatase inhibitor related musculoskeletal symptoms
AU - Stephanie Rosenberg
AU - Tomas Escobar Gil
AU - Jacklyn Nemunaitis
PY - 2026
DA - 2026/05/26
JO - Translational Breast Cancer Research
DO - 10.21037/tbcr-2026-1-0004
UR - https://doi.org/10.21037/tbcr-2026-1-0004
AB - Background: Aromatase inhibitors (AIs) are standard adjuvant therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer, yet up to half experience aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) that reduce quality of life and compromise adherence. We aim to better understand the biologic and imaging factors involved in AIMSS, which may improve early identification and management of these toxicities. Methods: We conducted a scoping review of studies published between 2010 and 2025 examining the biologic and imaging markers associated with AIMSS in breast cancer patients. We followed PRISMA-ScR guidelines and searched PubMed, EMBASE, Cochrane, JAMA and MEDLINE for original studies assessing biomarkers or imaging modalities linked to AIMSS. Our search terms included: breast cancer, aromatase inhibitors, arthralgia, biomarkers, biological marker, inflammatory marker, imaging, radiology. Thirteen studies met inclusion criteria, with predominantly postmenopausal women aged 50–67 years with early-stage HR+ disease. Biomarker categories included inflammatory cytokines [C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1)], metabolic and lipidomic profile [oxylipins, 8-hydroxyeicosatetraenoic acid (8-HETE)], hormonal markers (estradiol, sex hormone-binding globulin) and genetic polymorphisms (CYP19A1, ESR1, HSD17B2). Results: Elevated inflammatory and metabolic markers and lower estradiol levels on AI treatment were associated with AIMSS in several studies, while genetic associations were inconsistent, though newer work identified variants such as HSD17B2. Imaging approaches included ultrasound, magnetic resonance imaging (MRI), and shear wave elastography (SWE), with early and serial imaging showing potential for detecting tendon or soft tissue changes preceding symptoms. SWE may be a quantifiable tool for identifying early biomechanical changes. One study highlighted body mass index (BMI) as a potential clinical factor and proposed insulin-like growth factor as an unmeasured biomarker candidate. Conclusions: Overall, inflammatory and hormonal pathways, novel genetic variants, and early imaging changes represent promising approaches for understanding AIMSS. Larger, standardized studies that integrate these biologic and imaging data are needed to improve risk prediction and support adherence to endocrine therapy.
SN - 2218-6778
ER -