Role of dietary fatty acids in breast cancer: Molecular approaches

Epidemiological and experimental studies in the past have demonstrated a close association between increased consumption of dietary fat and the risk of breast cancer. Both in vitro and in vivo studies demonstrated the tumor promoting activity of linoleic acid (18:2) from vegetable oils. In contrast, the role of other fatty acids, such as ω-3 fatty acids (eicosapentaenoic acid 20:5, and docosahexanoic acid, 22:6) and conjugated linoleic acid (geometric isomer of linoleic acid), appears to have beneficial effects against breast cancer. While the role of these fatty acids in breast cancer, particularly in rodent models, is well established, very little information is available on the mechanism by which these fatty acids can alter the tumorigenesis. Recent findings suggest that the role of various dietary fatty acids, including reduced calorie intake, act on the regulation of gene transcription and/or translation activities. Involvement of several oncogenes, such as c-myc, c-ras, c-erbB-2/neu and p53, during the process of initiation and progression of mammary tumors are found to be regulated under the influence of dietary lipids. However, systematic studies are needed to establish the specific role of each fatty acid and its metabolised products, including various lipid mediators as second messengers in various signal transduction and apoptosis pathways that are involved in breast cancer. Our ongoing studies, and the findings of several other investigators in general, suggest that well-defined dietary fatty acids such as both CLA and ω-3 fatty acids may have a great potential for prevention and/or therapeutic intervention against malignancy, including reduction of side-effects of cytotoxic drugs against normal host tissues during the treatment of breast cancer and/or its metastasis.