Intraductal patient derived xenografts of estrogen receptor positive (ER+) breast cancer recapitulate the histopathological spectrum and metastatic potential of human lesions

Abstract

AbstractEstrogen receptor α positive (ER+) or “luminal” breast cancers were notoriously difficult to establish as patient-derived xenografts (PDXs). We and others recently demonstrated that the microenvironment is critical for ER+ tumor cells; by grafting them into milk ducts >90% take rates are achieved and many features of the human disease are recapitulated. 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 appearin situ. Tumor extent, histopathological patterns, and metastatic load correlate with biological properties of their tumors of origin. Our findings add evidence to the validity of the intraductal model forin vivostudies of ER+ breast cancer and raise the intriguing possibility that tumor cell dissemination may occur earlier than currently thought.Conflict of interest statement:The authors declare no conflict of interest.