Letters in Functional Foods · May 7, 2026
Dietary Polyunsaturated Fatty Acids as Risk Modifiers of Breast Cancer
By Kumar BVS, BISWAL JK
Introduction: Among all the polyunsaturated fatty acids (PUFAs), omega-3 (ω-3) PUFAs exhibit anti-inflammatory and anti-proliferative effects, whereas omega-6 (ω-6) PUFAs are generally pro-inflammatory and promote breast cancer cell growth. The present review aimed to elaborate on the roles of PUFAs as dietary risk modifiers of breast cancer and to highlight the underlying molecular mechanisms influencing tumor initiation and progression. Methods: A systematic literature search was conducted to identify relevant publications from 2000 to 2025 across major databases. Specific keywords such as ‘nutrition and cancer’, ‘breast cancer’, ‘polyunsaturated fatty acids’, ‘ω-3 PUFAs’, ‘ω-6 PUFAs’, ‘mammary gland’, and ‘breast cancer risk modifiers’ were used during the literature search. Results: We have systematically reviewed all relevant studies emphasizing the roles of dietary PUFAs in breast cancer incidence, progression, and prognosis. ω-6 PUFAs promote carcinogenesis by producing pro-inflammatory eicosanoids like prostaglandin E2 and leukotriene B4, activating nuclear factor kappa B (NF-κB) signaling, and upregulating the expression of proto-oncogenes and angiogenic factors. In contrast, ω-3 PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) inhibit tumor growth by incorporating into cell membranes, modulating lipid raft integrity, suppressing inflammatory signaling, and inducing apoptosis and cell-cycle arrest. Discussion: Emerging evidence suggests that ω-3 PUFAs regulate epigenetic modifications and alter gene expression related to cell differentiation and metastasis. Furthermore, the time and duration of exposure to dietary PUFAs play a critical role in modulating cancer susceptibility at different stages of mammary gland development, including puberty, pregnancy, and menopause. Conclusion: The dietary ω-6/ω-3 PUFA ratio is closely associated with breast cancer risk and progression. Maintaining an optimal ω-6/ω-3 ratio through dietary modification may serve as an effective preventive and therapeutic strategy against breast cancer. Future studies should focus on identifying optimal intake ratios, elucidating molecular targets, and translating preclinical findings into clinical interventions.