title: Systemic spread is an early step in breast cancer.
abstract: It is widely accepted that metastasis is a late event in cancer progression. Here, however, we show that tumor cells can disseminate systemically from earliest epithelial alterations in HER-2 and PyMT transgenic mice and from ductal carcinoma in situ in women. Wild-type mice transplanted with single premalignant HER-2 transgenic glands displayed disseminated tumor cells and micrometastasis in bone marrow and lungs. The number of disseminated cancer cells and their karyotypic abnormalities were similar for small and large tumors in patients and mouse models. When activated by bone marrow transplantation into wild-type recipients, 80 early-disseminated cancer cells sufficed to induce lethal carcinosis. Therefore, release from dormancy of early-disseminated cancer cells may frequently account for metachronous metastasis.
authors.affiliation: Department of Pathology, Division of Oncogenomics, University of Regensburg, Regensburg 93053, Germany.
authors.forename: Yves
authors.initials: Y
authors.lastname: Hüsemann
authors.forename: Jochen B
authors.initials: JB
authors.lastname: Geigl
authors.forename: Falk
authors.initials: F
authors.lastname: Schubert
authors.forename: Piero
authors.initials: P
authors.lastname: Musiani
authors.forename: Manfred
authors.initials: M
authors.lastname: Meyer
authors.forename: Elke
authors.initials: E
authors.lastname: Burghart
authors.forename: Guido
authors.initials: G
authors.lastname: Forni
authors.forename: Roland
authors.initials: R
authors.lastname: Eils
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Gert
authors.initials: G
authors.lastname: Riethmüller
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Klein
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007621:Karyotyping; D008175:Lung Neoplasms / Q000556:secondary; D008321:Mammary Glands, Animal / Q000637:transplantation / Q000648:ultrastructure; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*; D035781:Siblings