Mechanistic Links Between Obesity and Breast Cancer Progression - Cellular Crosstalk, Metabolic Reprogramming and Microenvironmental Drivers

Sep 22, 2026

Obesity is increasingly recognized as a driver of cancer progression, especially in breast cancer, yet the cellular and molecular mechanisms remain insufficiently defined. This review synthesizes current theories explaining how adipose tissue communicates with tumors through local and distant crosstalk. It emphasizes inflammation, oxidative stress, metabolic reprogramming, and the tumour microenvironment. The interactions vary with adipose tissue type and anatomical location, shaping breast cancer risk and outcomes and informing targeted therapy development.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Introduction

Methodology

Databases and search strategy

Inclusion criteria and study types

Summary

Cell Biochemistry and Function REVIEW ARTICLE Mechanistic Links Between Obesity and Breast Cancer Progression: Cellular Crosstalk, Metabolic Reprogramming and Microenvironmental Drivers Charlise Basson1,2 | Michael S. Pepper2 | Anna M. Joubert3 | Melvin A. Ambele1,2 1Department of Oral and Maxillofacial Pathology, School of Dentistry, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa | 2Department of Medical Immunology, Institute for Cellular and Molecular Medicine, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa | 3Department of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa Correspondence: Melvin A. Ambele ([melvin.ambele@up.ac.za](melvin.ambele@up.ac.za)) Received: 20 January 2026 | Revised: 5 June 2026 | Accepted: 1 July 2026 Funding: South African Medical Research Council University Flagship Project, Grant/Award Number: SAMRC‐RFA‐UFSP‐01‐2013/STEM CELLS; National Health Laboratory Service, Grant/Award Number: Grant004 94920; South African Medical Research Council, Grant/Award Number: A1H346 Keywords: adipokines | adipose tissue | breast cancer | cancer metabolism | obesity | oxidative stress | tumour microenvironment ABSTRACT Obesity is increasingly recognised as an important factor contributing to cancer progression, particularly in breast cancer. However, the cellular and molecular mechanisms underlying obesity‐driven breast cancer remain unclear. Several theories have been proposed to explain the complex interactions between adipose tissue and cancer, incorporating both local and distant crosstalk. This review describes existing theories on the cellular and molecular mechanisms linking obesity and breast cancer progression with a focus on inflammation, oxidative stress, metabolic reprogramming, the tumour microenvironment and crosstalk between adipose tissue and tumours. The nature of these interactions appears to be influenced by the specific characteristics of adipose tissue, including its type and anatomical location, which play distinct roles in modulating breast cancer risk and outcomes. Understanding the cellular and molecular mechanisms that underlie obesity‐driven breast cancer progression may pave the way for the development of targeted therapies. 1 | Introduction In addition to its well‐established effects on metabolic and general health, obesity is known to contribute to a number of malignancies, including breast cancer [ 1] . With both breast cancer mortality rates [2] and obesity incidence predicted to continue rising [3], there is an urgent need to understand the relationship between obesity and breast cancer. Obesity is believed to play a role in the incidence and progression of breast cancer [4] . However, the precise pathophysiological mechanisms by which obesity contributes to breast cancer initiation, progression and metastasis remain largely unclear [5] . Multiple theories have been proposed to explain the mechanisms by which obesity drives breast cancer progression. These theories focus on adipose tissue‐dependent secretion of molecules that may directly affect primary breast cancer tumours, alter the tumour microenvironment (TME), or prime secondary metastatic sites. These mechanisms are thought to be controlled by the adipose tissue‐dependent secretion of bioactive molecules, such as adipokines, cytokines and chemokines. However, these factors induce distinct effects based on their location and the type of adipose tissue from which they are secreted [6] . This review explores the current understanding of the molecular and microenvironmental mechanisms linking adiposity to This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2026 The Author(

FAQs

What is the main focus of this review?

The review explains cellular and molecular links between obesity and breast cancer progression, emphasizing cellular crosstalk, metabolic reprogramming, and microenvironmental drivers.

Which mechanisms are highlighted as key drivers of obesity-related breast cancer progression?

Inflammation, oxidative stress, metabolic reprogramming, and tumour microenvironment changes are presented as central mechanisms, shaped by adipose–tumour interactions.

How were studies selected for the narrative review?

The review searched PubMed, Scopus, and Web of Science using MeSH terms combined with AND/OR, and included English-language articles published from 2015 to 2025, with some earlier foundational studies added for conceptual clarity.

Sep 22, 2026

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