Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. Export

@article{citeulike:3352748, abstract = {PURPOSE: Breast cancer arising in young women is correlated with inferior survival and higher incidence of negative clinicopathologic features. The biology driving this aggressive disease has yet to be defined. PATIENTS AND METHODS: Clinically annotated, microarray data from 784 early-stage breast cancers were identified, and prospectively defined, age-specific cohorts (young: </= 45 years, n = 200; older: >/= 65 years, n = 211) were compared by prognosis, clinicopathologic variables, mRNA expression values, single-gene analysis, and gene set enrichment analysis (GSEA). Univariate and multivariate analyses were performed. RESULTS: Using clinicopathologic variables, young women illustrated lower estrogen receptor (ER) positivity (immunohistochemistry [IHC], P = .027), larger tumors (P = .012), higher human epidermal growth factor receptor 2 (HER-2) overexpression (IHC, P = .075), lymph node positivity (P = .008), higher grade tumors (P < .0001), and trends toward inferior disease-free survival (DFS; hazard ratio = 1.32; P = .094). Using genomic expression analysis, tumors arising in young women had significantly lower ERalpha mRNA (P < .0001), ERbeta (P = .02), and progesterone receptor (PR) expression (P < .0001), but higher HER-2 (P < .0001) and epidermal growth factor receptor (EGFR) expression (P < .0001). Exploratory analysis (GSEA) revealed 367 biologically relevant gene sets significantly distinguishing breast tumors arising in young women. Combining clinicopathologic and genomic variables among tumors arising in young women demonstrated that younger age and lower ERbeta and higher EGFR mRNA expression were significant predictors of inferior DFS. CONCLUSION: This large-scale genomic analysis illustrates that breast cancer arising in young women is a unique biologic entity driven by unifying oncogenic signaling pathways, is characterized by less hormone sensitivity and higher HER-2/EGFR expression, and warrants further study to offer this poor-prognosis group of women better preventative and therapeutic options.}, address = {Duke University Medical Center, Box 3841, 3829 Duke South, Red Zone, Durham, NC 27710, USA. ander118@mc.duke.edu}, author = {Anders, C. K. and Hsu, D. S. and Broadwater, G. and Acharya, C. R. and Foekens, J. A. and Zhang, Y. and Wang, Y. and Marcom, P. K. and Marks, J. R. and Febbo, P. G. and Nevins, J. R. and Potti, A. and Blackwell, K. L.}, citeulike-article-id = {3352748}, citeulike-linkout-0 = {http://dx.doi.org/10.1200/JCO.2007.14.2471}, citeulike-linkout-1 = {http://jco.ascopubs.org/cgi/content/abstract/26/20/3324}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18612148}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18612148}, day = {10}, doi = {10.1200/JCO.2007.14.2471}, issn = {1527-7755}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, keywords = {breast\_cancer, meta-analysis}, month = {July}, number = {20}, pages = {3324--3330}, posted-at = {2008-09-29 15:22:04}, priority = {2}, title = {Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression.}, url = {http://dx.doi.org/10.1200/JCO.2007.14.2471}, volume = {26}, year = {2008} }

TY - JOUR ID - citeulike:3352748 L3 - citeulike-article-id:3352748 N2 - PURPOSE: Breast cancer arising in young women is correlated with inferior survival and higher incidence of negative clinicopathologic features. The biology driving this aggressive disease has yet to be defined. PATIENTS AND METHODS: Clinically annotated, microarray data from 784 early-stage breast cancers were identified, and prospectively defined, age-specific cohorts (young: </= 45 years, n = 200; older: >/= 65 years, n = 211) were compared by prognosis, clinicopathologic variables, mRNA expression values, single-gene analysis, and gene set enrichment analysis (GSEA). Univariate and multivariate analyses were performed. RESULTS: Using clinicopathologic variables, young women illustrated lower estrogen receptor (ER) positivity (immunohistochemistry [IHC], P = .027), larger tumors (P = .012), higher human epidermal growth factor receptor 2 (HER-2) overexpression (IHC, P = .075), lymph node positivity (P = .008), higher grade tumors (P < .0001), and trends toward inferior disease-free survival (DFS; hazard ratio = 1.32; P = .094). Using genomic expression analysis, tumors arising in young women had significantly lower ERalpha mRNA (P < .0001), ERbeta (P = .02), and progesterone receptor (PR) expression (P < .0001), but higher HER-2 (P < .0001) and epidermal growth factor receptor (EGFR) expression (P < .0001). Exploratory analysis (GSEA) revealed 367 biologically relevant gene sets significantly distinguishing breast tumors arising in young women. Combining clinicopathologic and genomic variables among tumors arising in young women demonstrated that younger age and lower ERbeta and higher EGFR mRNA expression were significant predictors of inferior DFS. CONCLUSION: This large-scale genomic analysis illustrates that breast cancer arising in young women is a unique biologic entity driven by unifying oncogenic signaling pathways, is characterized by less hormone sensitivity and higher HER-2/EGFR expression, and warrants further study to offer this poor-prognosis group of women better preventative and therapeutic options. IS - 20 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology SN - 1527-7755 AD - Duke University Medical Center, Box 3841, 3829 Duke South, Red Zone, Durham, NC 27710, USA. ander118@mc.duke.edu EP - 3330 TI - Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. VL - 26 SP - 3324 KW - breast_cancer KW - meta-analysis AU - Anders, CK AU - Hsu, DS AU - Broadwater, G AU - Acharya, CR AU - Foekens, JA AU - Zhang, Y AU - Wang, Y AU - Marcom, PK AU - Marks, JR AU - Febbo, PG AU - Nevins, JR AU - Potti, A AU - Blackwell, KL PY - 2008/07/10/ UR - http://dx.doi.org/10.1200/JCO.2007.14.2471 ER -