title: A six-gene signature predicting breast cancer lung metastasis.
abstract: The lungs are a frequent target of metastatic breast cancer cells, but the underlying molecular mechanisms are unclear. All existing data were obtained either using statistical association between gene expression measurements found in primary tumors and clinical outcome, or using experimentally derived signatures from mouse tumor models. Here, we describe a distinct approach that consists of using tissue surgically resected from lung metastatic lesions and comparing their gene expression profiles with those from nonpulmonary sites, all coming from breast cancer patients. We show that the gene expression profiles of organ-specific metastatic lesions can be used to predict lung metastasis in breast cancer. We identified a set of 21 lung metastasis-associated genes. Using a cohort of 72 lymph node-negative breast cancer patients, we developed a 6-gene prognostic classifier that discriminated breast primary cancers with a significantly higher risk of lung metastasis. We then validated the predictive ability of the 6-gene signature in 3 independent cohorts of breast cancers consisting of a total of 721 patients. Finally, we show that the signature improves risk stratification independently of known standard clinical variables and a previously established lung metastasis signature based on an experimental breast cancer metastasis model.
authors.affiliation: Centre René Huguenin, Fédération Nationale des Centres de Lutte Contre le Cancer and Institut National de la Sante et de la Recherche Medicale, U735, Saint-Cloud, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Landemaine
authors.forename: Amanda
authors.initials: A
authors.lastname: Jackson
authors.forename: Akeila
authors.initials: A
authors.lastname: Bellahcène
authors.forename: Nadia
authors.initials: N
authors.lastname: Rucci
authors.forename: Soraya
authors.initials: S
authors.lastname: Sin
authors.forename: Berta Martin
authors.initials: BM
authors.lastname: Abad
authors.forename: Angels
authors.initials: A
authors.lastname: Sierra
authors.forename: Alain
authors.initials: A
authors.lastname: Boudinet
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Guinebretière
authors.forename: Enrico
authors.initials: E
authors.lastname: Ricevuto
authors.forename: Catherine
authors.initials: C
authors.lastname: Noguès
authors.forename: Marianne
authors.initials: M
authors.lastname: Briffod
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
authors.forename: Pascal
authors.initials: P
authors.lastname: Cherel
authors.forename: Teresa
authors.initials: T
authors.lastname: Garcia
authors.forename: Vincent
authors.initials: V
authors.lastname: Castronovo
authors.forename: Anna
authors.initials: A
authors.lastname: Teti
authors.forename: Rosette
authors.initials: R
authors.lastname: Lidereau
authors.forename: Keltouma
authors.initials: K
authors.lastname: Driouch
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction