Single-cell spatial atlas of the aging human breast

Abstract Breast cancer can develop over a wide age range and tumors in younger women differ from those in older women. Aging alters the spatial context of early tumors and may explain these differences, but breast tissue aging remains poorly characterized. Here, using imaging mass cytometry to profile the spatial expression of 40 proteins, we explore age-related remodeling of normal breast tissues in over 3 million cells from 527 reduction mammoplasties. Aged breast tissue was less cellular and less proliferative for all cell types (epithelial, stromal and immune). Tissue architecture was restructured with fewer heterotypic epithelial cell–cell interactions, far fewer lobules and increased fat. Older tissues had a more inflammatory microenvironment with increased M2 macrophages and granzyme B + T cells, contrasted by younger tissues in which B cells were most enriched. Our multiscale atlas extensively details an unexpected general decline of breast tissue with age and reveals its changing spatial context.