Taxonomy of breast cancer based on normal cell phenotype predicts outcome.

TitleTaxonomy of breast cancer based on normal cell phenotype predicts outcome.
Publication TypeJournal Article
Year of Publication2014
AuthorsSantagata S, Thakkar A, Ergonul A, Wang B, Woo T, Hu R, J Harrell C, McNamara G, Schwede M, Culhane AC, Kindelberger D, Rodig S, Richardson A, Schnitt SJ, Tamimi RM, Ince TA
JournalJ Clin Invest
Volume124
Issue2
Pagination859-70
Date Published2014 Feb
ISSN1558-8238
KeywordsAdolescent, Adult, Antigens, CD, Biomarkers, Breast, Breast Neoplasms, Cell Differentiation, Cell Line, Tumor, Cell Proliferation, Cohort Studies, Female, Gene Expression Profiling, Gene Expression Regulation, Hematopoiesis, Humans, Immunohistochemistry, Intermediate Filaments, Middle Aged, Phenotype, Prospective Studies, Receptors, Androgen, Receptors, Calcitriol, Receptors, Estrogen, Treatment Outcome, Young Adult
Abstract

Accurate classification is essential for understanding the pathophysiology of a disease and can inform therapeutic choices. For hematopoietic malignancies, a classification scheme based on the phenotypic similarity between tumor cells and normal cells has been successfully used to define tumor subtypes; however, use of normal cell types as a reference by which to classify solid tumors has not been widely emulated, in part due to more limited understanding of epithelial cell differentiation compared with hematopoiesis. To provide a better definition of the subtypes of epithelial cells comprising the breast epithelium, we performed a systematic analysis of a large set of breast epithelial markers in more than 15,000 normal breast cells, which identified 11 differentiation states for normal luminal cells. We then applied information from this analysis to classify human breast tumors based on normal cell types into 4 major subtypes, HR0-HR3, which were differentiated by vitamin D, androgen, and estrogen hormone receptor (HR) expression. Examination of 3,157 human breast tumors revealed that these HR subtypes were distinct from the current classification scheme, which is based on estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Patient outcomes were best when tumors expressed all 3 hormone receptors (subtype HR3) and worst when they expressed none of the receptors (subtype HR0). Together, these data provide an ontological classification scheme associated with patient survival differences and provides actionable insights for treating breast tumors.

DOI10.1172/JCI70941
Alternate JournalJ Clin Invest
PubMed ID24463450
Grant ListR01-CA146445-01 / CA / NCI NIH HHS / United States
K08NS064168 / NS / NINDS NIH HHS / United States
BC-07456 / BC / NCI NIH HHS / United States
Related Faculty: 
Tan Ince, M.D., Ph.D.

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