142P - Lipidomic signature in response to omega-3 fatty acids and γ-linolenic acid supplementation in breast cancer patients receiving aromatase inhibitors

Background

Lipid metabolic reprogramming is a prominent feature in cancer, influenced further by endocrine therapies in cancer patients. In breast cancer (BRC), levels of omega-3 fatty acids and γ-linolenic acid (GLA) are significantly lower compared to healthy women. Here we conducted a high throughput lipidomic profiling on BRC patients supplemented with omega-3 fatty acids and GLA.

Methods

A randomized controlled trial included 59 postmenopausal BRC patients, among whom 29 were receiving adjuvant hormonal therapy with aromatase inhibitors (AI). Both BRC and AI groups were divided into intervention groups (AI,n=15; BRC, n=15) receiving daily fish oil (600 μg eicosapentaenoic acid; EPA and 400 μg docosahexaenoic acid; DHA) and evening primrose oil (351 μg GLA) for 16 weeks, and control groups (AI, n=14; BRC, n=15) receiving placebo. Comprehensive targeted lipidomic analysis was conducted, semiquantifying over 700 lipids in plasma.

Results

The AI intervention group exhibited distinct lipidomic profiles characterized by increased levels of lysophosphatidylcholines (LPC) containing EPA and DHA (LPC 20:5 and LPC 22:6, respectively), and decreased levels of specific glycerophospholipids (phosphatidylcholines and phosphatidylethanolamines) and triacylglycerols incorporating docosatetraenoic acid (DTA 22:4). Free fatty acid forms of docosapentaenoic acid (DPA 22:5) and DHA were also elevated in this group. However, plasma lipids containing GLA did not increase despite supplementation. No significant changes were observed in the control groups. In the age-matched BRC subgroup not yet receiving AI therapy but with similar cancer type and stage, supplementation resulted in EPA and DHA incorporation primarily into triacylglycerols and cholesteryl esters.

Conclusions

Our findings illustrate altered lipid metabolism in BRC patients undergoing AI therapy, highlighting the dynamics of fatty acid metabolism and remodeling of lipid acyl chains towards increased LPC. These insights contribute to the foundation for precision medicine.

Editorial acknowledgement

Clinical trial identification

NCT06214598; Released 19.1.2024.

Legal entity responsible for the study

Institute for Medical Research, University of Belgrade.

Funding

Science fund of the Republic of Serbia and cost action CA19105 Pan-European Network in Lipidomics and EpiLipidomics (EpiLipidNET).

Disclosure

All authors have declared no conflicts of interest.