title: Abrogated response to cellular stress identifies DCIS associated with subsequent tumor events and defines basal-like breast tumors.
abstract: Approximately 15%-30% of women diagnosed with ductal carcinoma in situ (DCIS) develop a subsequent tumor event within 10 years after surgical lumpectomy. To date, little is known about the molecular pathways that confer this differential risk for developing subsequent disease. In this study, we demonstrate that expression of biomarkers indicative of an abrogated response to cellular stress predicts DCIS with worse outcome and is a defining characteristic of basal-like invasive tumors. Mechanistic studies identify the Rb pathway as a key regulator of this response. Conversely, biomarkers indicative of an intact response to cellular stress are strongly associated with a disease-free prognosis. Assessment of these biomarkers in DCIS begins to allow prediction of tumor formation years before it actually occurs.
authors.affiliation: Department of Pathology, University of California, San Francisco, CA 94143, USA.
authors.forename: Mona L
authors.initials: ML
authors.lastname: Gauthier
authors.forename: Hal K
authors.initials: HK
authors.lastname: Berman
authors.forename: Caroline
authors.initials: C
authors.lastname: Miller
authors.forename: Krystyna
authors.initials: K
authors.lastname: Kozakeiwicz
authors.forename: Karen
authors.initials: K
authors.lastname: Chew
authors.forename: Dan
authors.initials: D
authors.lastname: Moore
authors.forename: Joseph
authors.initials: J
authors.lastname: Rabban
authors.forename: Yunn Yi
authors.initials: YY
authors.lastname: Chen
authors.forename: Karla
authors.initials: K
authors.lastname: Kerlikowske
authors.forename: Thea D
authors.initials: TD
authors.lastname: Tlsty
mesh_terms: D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle; D049109:Cell Proliferation; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D008954:Models, Biological; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D012306:Risk; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D051546:Cyclooxygenase 2