Obesity and Breast Cancer Risk: The Oncogenic Implications of Metabolic Dysregulation

Abstract

Context: Breast cancer is increasing in prevalence in parallel with rising rates of obesity worldwide. Obesity is recognized as a leading modifiable risk factor for the development of breast cancer; however, this association varies considerably by clinicopathologic features, and the underlying mechanisms are complex. Evidence Acquisition: Pubmed literature search using combinations of "obesity,""breast cancer risk,""diet,""exercise,""weight gain,""weight loss,""adipose tissue inflammation,""crown-like structure,""immune markers,""metformin,""gliflozins,""SGLT-2i,""GLP1-RA,"and related terms. Evidence Synthesis: Elevated body mass index and weight gain are associated with increased risk of postmenopausal, hormone receptor- positive breast cancer. Emerging evidence suggests that adverse measures of body composition in individuals of any weight can also confer increased breast cancer risk. Mechanistically, various factors including altered adipokine balance, dysfunctional adipose tissue, dysregulated insulin signaling, and chronic inflammation contribute to tumorigenesis. Weight loss and more specifically fat mass loss through lifestyle and pharmacologic interventions improve serum metabolic and inflammatory markers, sex hormone levels, and measures of breast density, suggesting a link to decreased breast cancer risk. Conclusion: Incorporating markers of metabolic health and body composition measures with body mass index can capture breast cancer risk more comprehensively. Further studies of interventions targeting body fat levels are needed to curb the growing prevalence of obesity-related cancer.