Obesity-Related Mechanisms in Breast Cancer

Obesity constitutes a major modifiable risk factor for breast cancer, acting through a constellation of interrelated mechanisms that span endocrine, metabolic and inflammatory pathways. Excess adiposity drives upregulation of aromatase activity in adipose depots, elevating local and systemic oestrogen levels and thereby promoting the growth of hormone-dependent tumours. In parallel, chronic low-grade inflammation emerges through recruitment and activation of adipose tissue macrophages, formation of crown-like structures and secretion of pro-inflammatory cytokines, which together remodel the tumour microenvironment to support proliferation, invasion and angiogenesis. Insulin resistance and hyperinsulinaemia further exacerbate tumour cell signalling via insulin and IGF receptors, while adipokines such as leptin and adiponectin modulate cancer cell metabolism and immune surveillance. These processes contribute to molecular heterogeneity across breast cancer subtypes, influencing prognosis, therapeutic response and the propensity for metastatic spread. Understanding these obesity-related pathways has global significance, guiding preventive strategies and enabling personalised interventions that encompass weight management, dietary modulation and targeted therapies.

Research from Nature Portfolio

Recent studies of primary breast tumours stratified by body mass index have revealed that obesity is associated with distinctive genomic and transcriptomic alterations. In a cohort exceeding two thousand cases, increased adiposity correlated with a pattern of accelerated genetic ageing alongside subtle but discernible shifts in single-cell profiles of stromal and immune compartments. Obese patients exhibited an unresolved inflammatory signature within the tumour microenvironment, marked by persistent pro-inflammatory cytokine expression and altered fibroblast-immune cell crosstalk, with notable differences according to oestrogen receptor status. These findings underscore an inflammaging-like phenotype in breast cancer and support the integration of adiposity metrics into risk assessment and treatment stratification.

Obesity-Related Mechanisms in Breast Cancer publication trend

The graph below shows the total number of articles in obesity-related mechanisms in breast cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Adipose tissue macrophages (ATMs): Immune cells in fat tissue that adopt pro-inflammatory phenotypes and secrete cytokines influencing tumour progression.

Crown-like structures (CLS): Microscopic foci of dead or dying adipocytes encircled by macrophages, indicative of local adipose inflammation.

Inflammaging: Age-like chronic inflammatory state characterised by sustained, low-grade cytokine production in tissues.

Tumour microenvironment (TME): The cellular and molecular milieu surrounding a tumour, including immune cells, fibroblasts and extracellular matrix.

Aromatase: Enzyme that converts androgens to oestrogens, upregulated in adipose tissue of obese individuals.

References

1. Adipose tissue macrophages: implications for obesity-associated cancer. Military Medical Research (2023).
2. Obesity-associated changes in molecular biology of primary breast cancer. Nature Communications (2023).
3. Calorie restriction outperforms bariatric surgery in a murine model of obesity and triple-negative breast cancer. JCI Insight (2023).
4. The Interactions of Obesity, Inflammation and Insulin Resistance in Breast Cancer. Cancers (2015).
5. The obesity-breast cancer link: a multidisciplinary perspective. Cancer and Metastasis Reviews (2022).
6. Obesity and Cancer Metabolism: A Perspective on Interacting Tumor–Intrinsic and Extrinsic Factors. Frontiers in Oncology (2017).