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An integration of complementary strategies for gene-expression analysis to reveal novel therapeutic opportunities for breast cancer.

Publication ,  Journal Article
Bild, AH; Parker, JS; Gustafson, AM; Acharya, CR; Hoadley, KA; Anders, C; Marcom, PK; Carey, LA; Potti, A; Nevins, JR; Perou, CM
Published in: Breast Cancer Res
2009

INTRODUCTION: Perhaps the major challenge in developing more effective therapeutic strategies for the treatment of breast cancer patients is confronting the heterogeneity of the disease, recognizing that breast cancer is not one disease but multiple disorders with distinct underlying mechanisms. Gene-expression profiling studies have been used to dissect this complexity, and our previous studies identified a series of intrinsic subtypes of breast cancer that define distinct populations of patients with respect to survival. Additional work has also used signatures of oncogenic pathway deregulation to dissect breast cancer heterogeneity as well as to suggest therapeutic opportunities linked to pathway activation. METHODS: We used genomic analyses to identify relations between breast cancer subtypes, pathway deregulation, and drug sensitivity. For these studies, we use three independent breast cancer gene-expression data sets to measure an individual tumor phenotype. Correlation between pathway status and subtype are examined and linked to predictions for response to conventional chemotherapies. RESULTS: We reveal patterns of pathway activation characteristic of each molecular breast cancer subtype, including within the more aggressive subtypes in which novel therapeutic opportunities are critically needed. Whereas some oncogenic pathways have high correlations to breast cancer subtype (RAS, CTNNB1, p53, HER1), others have high variability of activity within a specific subtype (MYC, E2F3, SRC), reflecting biology independent of common clinical factors. Additionally, we combined these analyses with predictions of sensitivity to commonly used cytotoxic chemotherapies to provide additional opportunities for therapeutics specific to the intrinsic subtype that might be better aligned with the characteristics of the individual patient. CONCLUSIONS: Genomic analyses can be used to dissect the heterogeneity of breast cancer. We use an integrated analysis of breast cancer that combines independent methods of genomic analyses to highlight the complexity of signaling pathways underlying different breast cancer phenotypes and to identify optimal therapeutic opportunities.

Duke Scholars

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Published In

Breast Cancer Res

DOI

EISSN

1465-542X

Publication Date

2009

Volume

11

Issue

4

Start / End Page

R55

Location

England

Related Subject Headings

  • Signal Transduction
  • Phenotype
  • Oncology & Carcinogenesis
  • Oncogenes
  • Oligonucleotide Array Sequence Analysis
  • Neoplasm Proteins
  • Metabolic Networks and Pathways
  • Humans
  • Genetic Heterogeneity
  • Gene Regulatory Networks
 

Citation

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Bild, A. H., Parker, J. S., Gustafson, A. M., Acharya, C. R., Hoadley, K. A., Anders, C., … Perou, C. M. (2009). An integration of complementary strategies for gene-expression analysis to reveal novel therapeutic opportunities for breast cancer. Breast Cancer Res, 11(4), R55. https://doi.org/10.1186/bcr2344
Bild, Andrea H., Joel S. Parker, Adam M. Gustafson, Chaitanya R. Acharya, Katherine A. Hoadley, Carey Anders, P Kelly Marcom, et al. “An integration of complementary strategies for gene-expression analysis to reveal novel therapeutic opportunities for breast cancer.Breast Cancer Res 11, no. 4 (2009): R55. https://doi.org/10.1186/bcr2344.
Bild AH, Parker JS, Gustafson AM, Acharya CR, Hoadley KA, Anders C, et al. An integration of complementary strategies for gene-expression analysis to reveal novel therapeutic opportunities for breast cancer. Breast Cancer Res. 2009;11(4):R55.
Bild, Andrea H., et al. “An integration of complementary strategies for gene-expression analysis to reveal novel therapeutic opportunities for breast cancer.Breast Cancer Res, vol. 11, no. 4, 2009, p. R55. Pubmed, doi:10.1186/bcr2344.
Bild AH, Parker JS, Gustafson AM, Acharya CR, Hoadley KA, Anders C, Marcom PK, Carey LA, Potti A, Nevins JR, Perou CM. An integration of complementary strategies for gene-expression analysis to reveal novel therapeutic opportunities for breast cancer. Breast Cancer Res. 2009;11(4):R55.

Published In

Breast Cancer Res

DOI

EISSN

1465-542X

Publication Date

2009

Volume

11

Issue

4

Start / End Page

R55

Location

England

Related Subject Headings

  • Signal Transduction
  • Phenotype
  • Oncology & Carcinogenesis
  • Oncogenes
  • Oligonucleotide Array Sequence Analysis
  • Neoplasm Proteins
  • Metabolic Networks and Pathways
  • Humans
  • Genetic Heterogeneity
  • Gene Regulatory Networks