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The mammary ducts create a favourable microenvironment for xenografting of luminal and molecular apocrine breast tumours
Author(s) -
Richard Elodie,
Grellety Thomas,
Velasco Valerie,
MacGrogan Gaetan,
Bonnefoi Hervé,
Iggo Richard
Publication year - 2016
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4772
Subject(s) - apocrine , cancer research , androgen receptor , receptor , medicine , mammary gland , tumor microenvironment , hormone receptor , pathology , breast cancer , biology , cancer , prostate cancer
There is a paucity of models for hormone receptor‐positive ( HR +) breast cancer because of the difficulty of establishing xenografts from these tumours. We show that this obstacle can be overcome by injecting human tumour cells directly into the mammary ducts of immunodeficient mice. Tumours from 31 patients were infected overnight with a lentiviral vector expressing tdTomato and injected through the nipple into the mammary ducts of NOD‐SCID‐IL2RG −/− mice. Tumours formed in the mice in 77% of cases after the first injection (6/8 luminal A, 15/20 luminal B, and 3/3 molecular apocrine). Four luminal A and one molecular apocrine graft were tested in secondary and tertiary grafts: all were successfully passaged in secondary and 4/5 in tertiary grafts. None of the samples engrafted when injected subcutaneously. The morphology, oestrogen receptor ( ER ), progesterone receptor ( PR ), androgen receptor ( AR ), and Ki‐67 profiles of the clinical samples were maintained in the tertiary grafts. We also show that the intraductal approach can be used to test the response to targeted therapy with fulvestrant and palbociclib, using a genetically defined ER + model. We conclude that the mammary ducts create a microenvironment that is uniquely favourable to the survival and growth of tumours derived from mammary hormone‐sensing cells. This approach opens the door to testing genomically targeted treatment of HR + tumours in precision medicine programmes. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.