(P30-03-26) Alterations in the Plasma Lipidome and Links to Clinical Assessments During Breast Cancer Treatment

Objectives: Anthracycline-based chemotherapies (anth-bc) reduce left ventricular ejection fraction (LVEF) and exercise capacity placing breast cancer (BC) survivors at an increased risk of heart failure. Application of untargeted lipidomics can identify plasma lipids altered by anth-bc to serve as nutritional targets that attenuate declines in clinical assessments.

Methods: This study was conducted through the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base (NCT02791581). In 100 women with stage I-III BC, plasma samples were obtained prior to initiating anth-bc and 3 months later. Plasma samples were subjected to untargeted lipidomics analyses using a liquid chromatography-tandem mass spectrometry.  Submaximal exercise capacity was assessed by the six-minute walk distance (6MWD) test. LVEF was determined from cardiovascular magnetic resonance imaging. Post-hoc analyses with clinical assessments were adjusted for age, race, and body mass index.

Results: Participants averaged 53 years old (SD 11.4) with a mean body mass index of 28.6 ± 6.1 kg/m², and 78% reported White race. Of 10,277 lipid features detected, 958 were altered from before chemotherapy initiation to 3-months follow-up (FDR q < 0.05). Phosphatidylcholines and sphingomyelins were the predominant lipid classes altered. Lipids containing arachidonic acid (FA 20:4) side chains, and a specific sphingomyelin species [SM(36:2)] were associated with worse declines in 6MWD (p=0.01 and 0.04, respectively) while higher amounts of monounsaturated fatty acid side chains in circulating lipids were associated with better 6MWD at 3-months (p=0.01). Additionally, sphingolipids such as a ceramide [Hex2Cer(34:1)] and a sphingomyelin [SM(33:2)] were associated with greater declines in LVEF (p=0.01 and p=0.006, respectively).

Conclusions: The plasma lipidome is acutely impacted by anth-bc in the first 3-months of treatment. Association of lipid changes to clinical outcomes may provide novel biomarkers for anth-bc cardiovascular outcomes.

Funding Sources: Provided by grants from the National Institutes of Health, VCU Health Pauley Heart Center, and Susan G. Komen Foundation.