Adipokine Influence on Breast Cancer Risk

Adipose tissue functions as a dynamic endocrine organ, secreting a diverse array of bioactive peptides known as adipokines that modulate inflammation, metabolism and cellular proliferation. In breast cancer, dysregulated adipokine profiles—particularly elevated leptin and reduced adiponectin—contribute to a pro-tumourigenic microenvironment through activation of key signalling pathways such as JAK/STAT, PI3K/Akt and NFκB. Concurrent insulin resistance and chronic low-grade inflammation amplify growth-promoting signals, while cross-talk between adipocytes and cancer cells via extracellular vesicles reshapes gene expression towards invasion and metastasis. Central obesity further exacerbates these effects, linking fat distribution to hormone production and oxidative stress. Collectively, these interwoven mechanisms underscore the global significance of adipokines as both biomarkers of prognosis and potential therapeutic targets in breast cancer management.

Research from Nature Portfolio

A large multicentre prospective cohort study has demonstrated that systemic inflammation markers and insulin-resistance indices predict survival outcomes in women with breast cancer across different body mass indexes. Elevated C-reactive protein to albumin ratio and lipid-related ratios were independently associated with poorer prognosis, while combinations of lymphocyte-to-CRP and cholesterol-to-HDL ratios refined risk stratification in overweight and obese subgroups. An earlier nested case-control investigation within a major European cohort revealed that plasma levels of C-reactive protein, tumour necrosis factor-α and interleukin-6, alongside leptin and adiponectin, exhibit distinct associations with breast cancer risk according to menopausal status. Among postmenopausal women, high CRP and low adiponectin correlated with increased incidence, whereas in premenopausal women elevated TNF-α and altered leptin levels were more predictive of risk, providing evidence that inflammation-adipokine interplay is context-dependent.

Adipokine Influence on Breast Cancer Risk publication trend

The graph below shows the total number of articles in adipokine influence on breast cancer risk across all publications each year (not limited to Nature Index journals).

Technical terms

Adipokine: A hormone-like protein secreted by adipose tissue that regulates metabolism, inflammation and cell growth.

Leptin: An adipokine that signals energy sufficiency and can promote angiogenesis, proliferation and migration in cancer cells.

Adiponectin: An adipokine with anti-inflammatory and potentially tumour-suppressive effects, often reduced in obesity.

Visfatin: Also known as nicotinamide phosphoribosyltransferase, an adipokine involved in NAD+ metabolism and cancer stem cell activation.

C-reactive protein (CRP): An acute-phase protein produced by the liver as a systemic marker of inflammation.

Insulin resistance: A metabolic condition in which cells respond poorly to insulin, leading to compensatory hyperinsulinaemia and growth factor signalling.

Cancer stem cell (CSC): A subpopulation of tumour cells with self-renewal capacity and resistance to conventional therapies, driving recurrence.

References

1. 1α,25-Dihydroxyvitamin D Downregulates Adipocyte Impact on Breast Cancer Cell Migration and Adipokine Release. Nutrients (2024).
2. Updated Clinical Evidence on the Role of Adipokines and Breast Cancer: A Review. Cancers (2023).
3. Comprehensive prognostic effects of systemic inflammation and Insulin resistance in women with breast cancer with different BMI: a prospective multicenter cohort. Scientific Reports (2023).
4. Biomarkers of inflammation and breast cancer risk: a case-control study nested in the EPIC-Varese cohort. Scientific Reports (2017).
5. The Adipokine Visfatin Modulates Cancer Stem Cell Properties in Triple-Negative Breast Cancer. Biomedicines (2023).
6. Molecular Links between Central Obesity and Breast Cancer. International Journal of Molecular Sciences (2019).