Field cancerization, accelerated aging, and immunosuppression: the rapid rise of hormone-sensitive and early-onset breast cancer

Breast cancer etiology traditionally emphasizes genetic mutations, hormonal dynamics, and tissue aging. However, recent decades have seen a steady rise in breast cancer with a growing proportion of these tumors exhibiting estrogen receptor-positive (ER + ) phenotypes along with an alarming rise in early-onset breast cancer occurring in individuals without a family history of the disease. While increased screening and lifestyle changes explain part of this trend, they do not fully account for the rising incidence, particularly among specific racial and geographic subgroups. We hypothesize that this rising trend in hormone-sensitive and early-onset cancers is a manifestation of chronic, cumulative environmental exposures, particularly to endocrine-disrupting chemicals (EDCs), that profoundly alter breast tissue biology. Since EDCs alter estrogen receptor signaling, the epigenetic landscape, and disrupt immune surveillance, we hypothesize that this may underpin the rising incidence of hormone-sensitive early-onset breast cancers through a mechanism that affects field cancerization and hormone-mediated aging.