Abrogated response to cellular stress identifies DCIS associated with subsequent tumor events and defines basal-like breast tumors.
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.
Gauthier
Mona L
ML
Department of Pathology, University of California, San Francisco, CA 94143, USA.
Berman
Hal K
HK
Miller
Caroline
C
Kozakeiwicz
Krystyna
K
Chew
Karen
K
Moore
Dan
D
Rabban
Joseph
J
Chen
Yunn Yi
YY
Kerlikowske
Karla
K
Tlsty
Thea D
TD
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
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D051546:Cyclooxygenase 2