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

Publication ,  Journal Article
Anders, CK; Hsu, DS; Broadwater, G; Acharya, CR; Foekens, JA; Zhang, Y; Wang, Y; Marcom, PK; Marks, JR; Febbo, PG; Nevins, JR; Potti, A; Blackwell, KL
Published in: J Clin Oncol
July 10, 2008

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: /= 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.

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Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

July 10, 2008

Volume

26

Issue

20

Start / End Page

3324 / 3330

Location

United States

Related Subject Headings

  • Survival Analysis
  • Risk Assessment
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Progesterone
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • RNA, Messenger
  • Prospective Studies
  • Prognosis
  • Probability
 

Citation

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MLA
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Anders, C. K., Hsu, D. S., Broadwater, G., Acharya, C. R., Foekens, J. A., Zhang, Y., … Blackwell, K. L. (2008). Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol, 26(20), 3324–3330. https://doi.org/10.1200/JCO.2007.14.2471
Anders, Carey K., David S. Hsu, Gloria Broadwater, Chaitanya R. Acharya, John A. Foekens, Yi Zhang, Yixin Wang, et al. “Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression.J Clin Oncol 26, no. 20 (July 10, 2008): 3324–30. https://doi.org/10.1200/JCO.2007.14.2471.
Anders CK, Hsu DS, Broadwater G, Acharya CR, Foekens JA, Zhang Y, et al. Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol. 2008 Jul 10;26(20):3324–30.
Anders, Carey K., et al. “Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression.J Clin Oncol, vol. 26, no. 20, July 2008, pp. 3324–30. Pubmed, doi:10.1200/JCO.2007.14.2471.
Anders CK, Hsu DS, Broadwater G, Acharya CR, Foekens JA, Zhang Y, Wang Y, Marcom PK, Marks JR, Febbo PG, Nevins JR, Potti A, Blackwell KL. Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol. 2008 Jul 10;26(20):3324–3330.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

July 10, 2008

Volume

26

Issue

20

Start / End Page

3324 / 3330

Location

United States

Related Subject Headings

  • Survival Analysis
  • Risk Assessment
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Progesterone
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • RNA, Messenger
  • Prospective Studies
  • Prognosis
  • Probability