ASPO Abstracts

Oxylipins Correlate with Quality of Life in Women Taking Aromatase Inhibitors for Breast Cancer

Authors: Martinez JA, Stopeck AT, Chow HHS, Wertheim BC, Chew W, Roe DJ, Chalasani P, and Thompson PA

Category: Survivorship & Health Outcomes/Comparative Effectiveness Research
Conference Year: 2020

Abstract Body:
The purpose of this study was to determine if oxylipins - oxygenated bioactive lipid metabolites of ω-3 and ω-6 fatty acids with varying roles in inflammation and pain - correlate with aromatase inhibitor-associated arthralgia (AIA) and quality of life (QOL) in early stage breast cancer (ESBC) patients. Methods: ESBC patients on AI therapy were enrolled to an open-label study of sulindac, a non-steroidal anti-inflammatory drug (NSAID), for 12 months (n = 47). Pre-intervention arthralgia and physical function were assessed using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) questionnaire, where higher scores indicate worse symptoms. The Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire was used to assess QOL, where higher scores indicate better QOL. A total of 53 plasma oxylipins in plasma were quantified by mass spectrometry. Pearson's correlation was used to measure the association between pre-intervention oxylipin concentrations, arthralgias and QOL. Results: Prior to initiating sulindac, baseline levels of 17 oxylipins were found to be significantly correlated with QOL scales. This included inverse associations between QOL and seven pro-inflammatory products of ω-6 fatty acid metabolism. Notably, prostaglandin E2, the primary target of NSAIDs, was negatively correlated with Social Well-Being (rho = -0.30; P = 0.04). Conversely, resolvin D1, a potent anti-inflammatory lipid, was positively associated with Total FACT-G (rho = 0.31; P = 0.03) and Emotional Well-Being (rho = 0.37; P = 0.01). Two ω-3 metabolites with unknown mechanisms were correlated with both QOL and WOMAC; 19,20-DiHDPE was positively correlated with Total (rho = 0.34; P = 0.02) and Social FACT-G (rho = 0.32; P = 0.03), and inversely with Total WOMAC (rho = -0.303; P = 0.04) and Stiffness (rho = -0.32; P = 0.03); and 5(6)-DiHETE was inversely correlated with Social FACT-G (rho = -0.33; P = 0.02) and positively with Total WOMAC (rho = 0.31; P = 0.04). Conclusions: This is the first evidence that plasma oxylipin metabolites of ω-3/ω-6 fatty acids correlate with QOL and arthralgia symptoms in patients on AIs and suggests oxylipins as a potential novel target for improving QOL and adherence to AI therapy in patients with ESBC.

Keywords: aromatase inhibitor arthralgias (AIA), breast cancer, oxylipins