title: The mammary ducts create a favourable microenvironment for xenografting of luminal and molecular apocrine breast tumours.
abstract: 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.
authors.affiliation: INSERM U1218, Bergonie Cancer Institute, University of Bordeaux, 33076, Bordeaux, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Richard
authors.affiliation: INSERM U1218, Bergonie Cancer Institute, University of Bordeaux, 33076, Bordeaux, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grellety
authors.affiliation: INSERM U1218, Bergonie Cancer Institute, University of Bordeaux, 33076, Bordeaux, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Velasco
authors.affiliation: INSERM U1218, Bergonie Cancer Institute, University of Bordeaux, 33076, Bordeaux, France.
authors.forename: Gaetan
authors.initials: G
authors.lastname: MacGrogan
authors.affiliation: INSERM U1218, Bergonie Cancer Institute, University of Bordeaux, 33076, Bordeaux, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Bonnefoi
authors.affiliation: INSERM U1218, Bergonie Cancer Institute, University of Bordeaux, 33076, Bordeaux, France. R.Iggo@bordeaux.unicancer.fr.
authors.forename: Richard
authors.initials: R
authors.lastname: Iggo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001050:Apocrine Glands / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D060833:Cellular Microenvironment; D004195:Disease Models, Animal; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D064593:Heterografts; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000473:pathology / Q000502:physiology*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000379:methods*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004958:Estradiol; D000077267:Fulvestrant; D019394:Ki-67 Antigen; D010879:Piperazines; D011725:Pyridines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C500026:palbociclib
keywords: intraductal xenograft; luminal breast cancer; molecular apocrine breast cancer; patient-derived xenograft (PDX)