(P13-028-23) Cancer Activity and Lifestyle Measurement Study: A Feasibility Study To Evaluate Mitochondrial Lipidome Changes After Anthracycline Treatment in Women With Breast Cancer

Objectives: Although anthracycline chemotherapy (AC) is highly effective in treating breast cancer, AC often has toxic effects in non-tumor, mitochondrial rich tissues including cardiac and skeletal muscle. AC inhibits topoisomerase 2 to impair the cell cycle and directly binds to cardiolipin (CL), a major phospholipid in the inner mitochondrial membrane. Disruption of CL leads to heart failure and skeletal muscle weakness. The primary fatty acyl in CL is linoleic acid (LA), an essential fatty acid in the human diet. With many heart diseases, oleic acid (OA) replaces LA on CL. Hypothesis: LA-rich CL (e.g., L4-CL) will be reduced in women after AC treatment.

Objective: Measure CL species before and after one cycle of AC treatment in peripheral blood mononuclear cells (PBMCs) from women with breast cancer.

Methods: Women, ages 18-95, with stage I-III breast cancer who were planning with their oncology team to undergo AC treatment were recruited. Before and after one cycle of AC treatment, body anthropometrics were measured, and blood samples were taken to isolate PBMCs and to measure serum lipids and markers of glycemia and inflammation. Participants were asked to complete questionnaires regarding diet, physical activity, and quality of life.

Results: Recruitment was difficult due to the narrow window of eligibility. 14 women were enrolled, 3 discontinued prior to starting the study and 3 discontinued before the final study measurements. Using a spaghetti plot analysis, the percent of L₄-CL (m/z 1448) decreased following treatment of AC, while the percent of LA₄OA₁-CL (m/z 1450) increased. The ratio of LA₄-CL:OA₄-CL also decreased following treatment. Future data analyses will evaluate body composition, RBC fatty acids, physical activity, and quality of life scores as modifiers of our findings.

Conclusions: Due to the difficulty of accrual, conducting this study at multiple sites would improve feasibility. It appears that after one treatment of AC, OA replaces LA in PBMC CL. If a larger trial shows similar findings to this study, a randomized controlled trial should test the effect of including seed oils high in LA to improve outcomes for breast cancer patients undergoing AC.

Funding Sources: This study was funded by NIH CA209566. We thank our participants for working with us and Dr. Michael Berger for support of our recruitment.