Fig. 2: Conceptual model linking environmental exposures to early onset breast cancer development.

A Schematic depicting how chronic exposure to EDCs reprograms estrogen receptor-positive (ER⁺) luminal epithelial cells in the mammary gland. In normal tissue, non-proliferative ER⁺ cells integrate hormonal signals to regulate proliferation of ER - cells. EDC exposure induces epigenetic changes, including altered DNA methylation and increased chromatin accessibility, promoting a more proliferative, plastic phenotype of ER⁺ luminal cells. Over time, this results in the emergence of a “cancerized field” of altered ER⁺ cells that are primed for transformation into aggressive luminal tumors. B Developmental timing of exposure shapes the extent of field cancerization. Illustrations show three critical windows of susceptibility—in utero, puberty, and pregnancy—during which environmental exposures may differentially impact mammary epithelial cell fate. Earlier exposures are hypothesized to result in more extensive field cancerization, as depicted by the gradient and corresponding cellular diagrams below.