Inflammation and immune dysregulation drive breast cancer in aging women

Age-related and postmenopausal breast cancer progression remains a significant challenge, with growing evidence pointing to the role of pro-inflammatory cytokines and CXC chemokines in tumor development and immune system modulation. As the global population ages, understanding the intricate connections between aging, inflammation, and cancer progression becomes increasingly critical.

The aging process is accompanied by changes in the tumor microenvironment, including the stiffening of the extracellular matrix and the accumulation of inflammatory immune mediators, such as interleukins (IL-6, IL-8), tumor necrosis factor (TNF), transforming growth factor (TGF), and CXC chemokines (CXCL1, CXCL9, CXCL10, CXCL11, CXCL12). These factors contribute to tumor growth, metastasis, and immune evasion, particularly in postmenopausal women.

Obesity-induced chronic inflammation further amplifies the risks, as excess adipose tissue leads to an overproduction of cytokines and adipokines. This inflammatory environment enhances tumor aggressiveness, influences immune cell infiltration, and modifies hormone signaling, thereby increasing breast cancer susceptibility in postmenopausal women. Studies have shown that elevated levels of CXCL8/IL-8 and CXCL12/CXCR4 correlate with tumor progression, making these key targets for potential therapeutic interventions.

A crucial aspect of age-related breast cancer progression is the dysregulation of the immune system, particularly the decline in tumor-infiltrating lymphocytes (TILs) and the impaired response to immune checkpoint inhibitors. The senescence-associated secretory phenotype (SASP), characterized by the release of inflammatory cytokines, plays a pivotal role in this process, contributing to both tumor growth and immune suppression. The pro-tumor effects of IL-6, IL-1β, and CXCLs highlight the importance of targeting cytokine-driven inflammation as a therapeutic strategy.

Advancements in theranostic interventions focusing on cytokine and chemokine modulation hold promise for improved breast cancer treatment in older women. By addressing the interplay between aging, obesity, inflammation, and immune function, researchers aim to develop personalized therapies that mitigate tumor progression while preserving immune surveillance.

With the rising incidence of postmenopausal breast cancer, the need for innovative approaches targeting inflammatory pathways has never been more pressing. By unraveling the complex molecular mechanisms underlying age-related cancer progression, the scientific community is paving the way for more effective and tailored treatment strategies that can significantly improve patient outcomes.