(P12-001-25) The Role of Omega-3 Polyunsaturated Fatty Acids in Modulating Inflammation and Breast Cancer: A Systematic Review of In Vitro, Animal, and Human Studies

Objectives: Inflammation is a hallmark of breast cancer (BC), that influences the tumor microenvironment (TME), immune evasion and tumor growth. n-3 polyunsaturated fatty acids (PUFA), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have anti-inflammatory and immunomodulatory effects, however, their precise impact on inflammation and immune function in BC remains unclear. Evidence is conflicted by variability in study outcomes, design, dosage, and formulations of n-3 PUFA utilized, complicating the understanding of mechanisms of action and therapeutic potential. This systematic review aimed to address these gaps by evaluating the effects of n-3 PUFA on inflammatory markers in BC.

Methods: A systematic search was conducted on PubMed, Web of Science, and the GOED (Global Organization for EPA and DHA) Clinical Study Database to identify preclinical and clinical studies investigating the effects of n-3 PUFA on inflammation and immune function in BC. Eligible studies were selected using predefined inclusion criteria (PROSPERO CRD42024499082) and assessed for risk of bias using Cochrane Handbook guidance. Primary outcomes included changes in cytokines, tumor-infiltrating immune cells, and inflammatory signaling pathways.

Results: Of the 807 articles screened, 61 met the inclusion criteria. Across study types, n-3 PUFA demonstrated significant anti-inflammatory and anti-tumoral effects. Clinical studies showed IL-6 levels decreased by 50-70% with n-3 PUFA supplementation. Preclinical studies reported significant reductions in proinflammatory cytokines (TNF-α, IL-6, CCL2), alongside increases in anti-inflammatory cytokines (IL-10, IL-2) with n-3 PUFA compared to control, and a 57-90% reduction of regulators and/or lipid mediators (COX-2, PGE₂). In vitro findings showed large decreases (–40-80%) in NF-κB and matrix metalloproteinase (MMP-2, -9) activity with n-3 PUFA treatment.

Conclusions: n-3 PUFA exhibit anti-inflammatory and immunomodulatory effects in BC, highlighting their potential as an adjuvant therapy to modulate the TME. Standardized research methodologies and clinical trials are needed to clarify dose-response relationships and therapeutic applications.

Funding Sources: Canadian Institutes of Health Research, Canadian Cancer Society and GOED for travel funding and access to the Clinical Study Database.