Intraductal patient‐derived xenografts of estrogen receptor α‐positive (ER+) breast cancer recapitulate the histopathological spectrum and metastatic potential of human lesions
Abstract
Estrogen receptor positive (ER+) or “luminal” breast cancers (BC) were notoriously difficult to
establish as patient-derived xenografts (PDXs). We and others recently demonstrated that the
microenvironment is critical for ER+ tumor cells; when grafted as single cells into milk ducts of NOD
Scid gamma (NSG) females >90% of ER+ tumors can be established as xenografts and recapitulate
many features of the human disease in vivo. This intra-ductal (ID) approach holds promise for
personalized medicine, yet human and murine stroma are organized differently and this and other
species specificities may limit the value of this model. Here, we analyzed 21 ER+ ID-PDXs
histopathologically. We find that ID-PDXs vary in extent and define four histopathological patterns:
flat, lobular, in situ, and invasive, which occur in pure and combined forms. The ID-PDXs replicate
earlier stages of tumor development than their clinical counterparts. Micrometastases are already
detected when lesions appear in situ. Tumor extent, histopathological patterns and micrometastatic
load correlate with biological properties of their tumors of origin. Our findings add evidence to the
validity of the intraductal model for in vivo studies of ER+ breast cancer and raise the intriguing
possibility that tumor cell dissemination may occur earlier than currently thought.
Origin : Files produced by the author(s)
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