Oxylipins as Biomarkers for Aromatase Inhibitor-Induced Arthralgia (AIA) in Breast Cancer Patients

Jessica A Martinez; Betsy C Wertheim; Denise J Roe; Mihra S Taljanovic; H-H Sherry Chow; Wade Chew; Sima Ehsani; Sao Jiralerspong; Jennifer Segar; Pavani Chalasani

doi:10.3390/metabo13030452

Oxylipins as Biomarkers for Aromatase Inhibitor-Induced Arthralgia (AIA) in Breast Cancer Patients

Metabolites. 2023 Mar 20;13(3):452. doi: 10.3390/metabo13030452.

Authors

Jessica A Martinez^{1

2}, Betsy C Wertheim¹, Denise J Roe^{1

3}, Mihra S Taljanovic⁴, H-H Sherry Chow¹, Wade Chew¹, Sima Ehsani^{1

5}, Sao Jiralerspong^{1

5}, Jennifer Segar^{1

5}, Pavani Chalasani^{1

5}

Affiliations

¹ The University of Arizona Cancer Center, Tucson, AZ 85724, USA.
² Department of Nutritional Sciences and Wellness, University of Arizona, Tucson, AZ 85724, USA.
³ Department of Epidemiology and Biostatistics, University of Arizona, Tucson, AZ 85724, USA.
⁴ Department of Radiology, University of New Mexico, Albuquerque, NM 87106, USA.
⁵ Department of Medicine, University of Arizona, Tucson, AZ 85724, USA.

Abstract

Aromatase inhibitor-induced arthralgia (AIA) presents a major problem for patients with breast cancer but is poorly understood. This prospective study explored the inflammatory metabolomic changes in the development of AIA. This single-arm, prospective clinical trial enrolled 28 postmenopausal women with early-stage (0-3) ER+ breast cancer starting adjuvant anastrozole. Patients completed the Breast Cancer Prevention Trial (BCPT) Symptom Checklist and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) at 0, 3, and 6 months. The plasma levels of four polyunsaturated fatty acids (PUFAs) and 48 oxylipins were quantified at each timepoint. The subscores for WOMAC-pain and stiffness as well as BCPT-total, hot flash, and musculoskeletal pain significantly increased from baseline to 6 months (all p < 0.05). PUFA and oxylipin levels were stable over time. The baseline levels of 8-HETE were positively associated with worsening BCPT-total, BCPT-hot flash, BCPT-musculoskeletal pain, WOMAC-pain, and WOMAC- stiffness at 6 months (all p < 0.05). Both 9-HOTrE and 13(S)-HOTrE were related to worsening hot flash, and 5-HETE was related to worsening stiffness (all p < 0.05). This is the first study to prospectively characterize oxylipin and PUFA levels in patients with breast cancer starting adjuvant anastrozole. The oxylipin 8-HETE should be investigated further as a potential biomarker for AIA.

Keywords: aromatase inhibitors; arthralgia; breast cancer; joint pain; oxylipins; stiffness.

Grants and funding

This research was funded by The University of Arizona Cancer Center, Clinical Research Oversight Counsel (CROC) grant and by the National Cancer Institute of the National Institutes of Health under award number P30 CA023074.