The Effects of Chemotherapy on Circulating Plasma Omega-9, Omega-3 Fatty Acids and Plasmalogen in Breast Cancer Patients

OBJECTIVES: Chemotherapy produces long-term cognitive impairment (CICI) in ∼30% of those receiving solid tumor treatment. Our previous results revealed a positive correlation between doxorubicin treatment and murine hippocampal concentrations of omega-9 fatty acids, relative to untreated controls. Our objective was to measure these and other structurally analogous fatty acids in human plasma following breast-cancer treatment, to determine if they might serve as biomarkers and/or nutritional targets during treatment. METHODS: Serum samples were collected from patients (n = 51) at ≥ 2 of 3 visits: immediately prior to standard adjuvant and neo-adjuvant chemotherapy for breast cancer (baseline), prior to the third cycle of chemotherapy, and 6 months after chemotherapy termination. Lipophilic extracts of serum were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to quantify eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA), linoleic acid, oleic acid, mead acid, gondoic acid, erucic acid, nervonic acid and PE(P-18:0/22:6) (plasmalogen). Linear models assessed the impact of visit on fatty acid concentrations, with a fixed intercept used for each subject. A P < 0.05 for chemotherapy was considered significant. RESULTS: Chemotherapy significantly increased plasma concentrations of gondoic, erucic, nervonic acids and plasmalogen (with no effect on the other fatty acids tested). Six months following chemotherapy, concentrations of gondoic, erucic, nervonic acids and plasmalogen approached baseline concentrations. CONCLUSIONS: Breast cancer chemotherapy significantly increased plasma concentrations of omega-9 fatty acids previously reported as increased in subjects with increasing severity of cognitive impairment and Alzheimer's disease. Ongoing work includes correlating the concentrations of these fatty acids with measures of memory and cognition. Future investigations will determine if these compounds may serve as nutritional targets for dietary interventions prior to or during chemotherapy treatment, and/or serve as objective biomarkers of CICI. FUNDING SOURCES: The Ohio State University Stefanie Spielman Breast Cancer Center Kroger Fund, Pelotonia, NIH R01CA189947, NIH Award Number Grant P30 CA016058, OSU, and OSUCCC.