(P12-019-25) Lipidomic Factors Predict Cardiotoxic Injury Following Anthracycline Chemotherapy in Women With Breast Cancer: A Feasibility Study

Objectives: Anthracycline chemotherapy (AC) leads to cardiotoxicity in many breast cancer patients by inducing inner mitochondrial damage and disrupting the electron transport chain.

This study was conducted to determine the feasibility of accrual and estimate the effect size of one cycle of AC on heart function and erythrocyte and mitochondrial lipidome changes in patients with breast cancer.

Methods: Women with stage I-III breast cancer who were planning with their oncology team to undergo AC treatment were recruited for this prospective feasibility study. Patients underwent blood sampling and cardiac magnetic resonance imaging at two clinical visits, before and after any one cycle of AC. Cardiac tissue level imaging using T1/T2-mapping was used to detect myocardial injury. HPLC-MS/MS was used for mitochondrial lipidomic analysis.

Results: Difficulty recruiting due to the timing of capturing newly diagnosed breast cancer patients, exacerbated by the COVID-19 pandemic, resulted in a total enrollment of 14 women, 3 who withdrew before starting the study, and 3 discontinued after visit 1.

After one cycle of AC, myocardial T2, a subclinical biomarker of myocardial injury and impending heart failure, significantly increased (p=0.031).

Targeted lipidomic analysis on cardiolipin (CL), the inner mitochondrial membrane phospholipid, revealed the ratio of LA₄ to oleic acid (OA₄) was negatively correlated with T1, an indicator of myocardial fibrosis, at visit 1 (p=0.026). OA₄CL, (%72 carbons), was positively associated with T1 at visit 1 (p=0.026) and visit 2 (p=0.019). OA content in erythrocytes was positively correlated with T2 at visit 1 (p=0.050) and visit 2 (p=0.011)

Conclusions: OA-rich CL and OA in erythrocytes appear to be related to subclinical markers of heart failure. We plan to test our hypothesis that dietary LA will preserve cardiac contractile function, mitochondrial function, and LA-rich and OA-poor CL species in mice with mammary cancer, treated with AC.

Funding Sources: This project was funded by NIH grant (NIH/NCI CA 206566) and in part supported by The Ohio State University Clinical and Translational Science Institute (CTSI) grant support (National Center for Advancing Translational Sciences, Grant UM1TR004548).