High-Fat Diet Effects on Mammary Tumorigenesis

High-fat diets have long been implicated in the initiation and progression of mammary tumours, acting through a constellation of metabolic, inflammatory and hormonal pathways. Experimental models demonstrate that diets enriched in saturated fats promote adipose tissue inflammation, characterised by macrophage infiltration and the formation of crown-like structures, which secrete pro-inflammatory cytokines such as interleukin-6 and monocyte chemoattractant protein-1. These mediators foster a microenvironment that supports angiogenesis, cell proliferation and evasion of immune surveillance. In carcinogen-induced and genetically driven mouse models, high-fat feeding reduces tumour latency and increases both primary tumour burden and distal metastasis, even in the absence of obesity. Mechanistically, dietary fat enhances expression of growth factors and adhesion molecules, remodels extracellular matrix and perturbs oestrogen signalling, further accelerating tumour growth. Although human epidemiological data have been mixed, there is mounting evidence that high intake of saturated fats during sensitive windows—such as puberty and premenopause—heightens breast cancer risk. Understanding these mechanisms has global significance for public health, informing dietary guidelines and potential interventions to mitigate breast cancer incidence through nutritional modification and anti-inflammatory strategies.

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High-Fat Diet Effects on Mammary Tumorigenesis publication trend

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Technical terms

Tumour latency: Interval between exposure to a carcinogenic stimulus or dietary intervention and the appearance of a palpable tumour.

Angiogenesis: Formation of new blood vessels from existing vasculature, crucial for supplying nutrients and oxygen to growing tumours.

Metastasis: Process by which cancer cells spread from the primary site to distant organs, establishing secondary tumours.

Crown-like structure (CLS): Histological formation in adipose tissue where macrophages surround necrotic adipocytes, indicative of chronic inflammation.

MMTV-PyMT model: Transgenic mouse line expressing the polyoma middle T oncoprotein under the mouse mammary tumour virus promoter, leading to spontaneous mammary tumours.

Xenograft: Transplantation of cells or tissues from one species into another to study tumour growth and therapeutic responses.

References

1. Dietary fat increases solid tumor growth and metastasis of 4T1 murine mammary carcinoma cells and mortality in obesity-resistant BALB/c mice. Breast Cancer Research (2011).
2. High-Fat, High-Calorie Diet Enhances Mammary Carcinogenesis and Local Inflammation in MMTV-PyMT Mouse Model of Breast Cancer. Cancers (2015).
3. Nutritional Regulation of Mammary Tumor Microenvironment. Frontiers in Cell and Developmental Biology (2022).