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Targeted biomarker profiling of matched primary and metastatic estrogen receptor positive breast cancers.

Abstract
Patients with newly diagnosed, early stage estrogen receptor positive (ER+) breast cancer often show disease free survival in excess of five years following surgery and systemic adjuvant therapy. An important question is whether diagnostic tumor tissue from the primary lesion offers an accurate molecular portrait of the cancer post recurrence and thus may be used for predictive diagnostic purposes for patients with relapsed, metastatic disease. As the class I phosphatidylinositol 3' kinase (PI3K) pathway is frequently activated in ER+ breast cancer and has been linked to acquired resistance to hormonal therapy, we hypothesized pathway status could evolve over time and treatment. Biomarker analyses were conducted on matched, asynchronous primary and metastatic tumors from 77 patients with ER+ breast cancer. We examined whether PIK3CA and AKT1 alterations or PTEN and Ki67 levels showed differences between primary and metastatic samples. We also sought to look more broadly at gene expression markers reflective of proliferation, molecular subtype, and key receptors and signaling pathways using an mRNA analysis platform developed on the Fluidigm BioMark™ microfluidics system to measure the relative expression of 90 breast cancer related genes in formalin-fixed paraffin-embedded (FFPE) tissue. Application of this panel of biomarker assays to matched tumor pairs showed a high concordance between primary and metastatic tissue, with generally few changes in mutation status, proliferative markers, or gene expression between matched samples. The collection of assays described here has been optimized for FFPE tissue and may have utility in exploratory analyses to identify patient subsets responsive to targeted therapies.
AuthorsErica B Schleifman, Rupal Desai, Jill M Spoerke, Yuanyuan Xiao, Cheryl Wong, Ilma Abbas, Carol O'Brien, Rajesh Patel, Teiko Sumiyoshi, Ling Fu, Rachel N Tam, Hartmut Koeppen, Timothy R Wilson, Rajiv Raja, Garret M Hampton, Mark R Lackner
JournalPloS one (PLoS One) Vol. 9 Issue 2 Pg. e88401 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID24520381 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Receptors, Estrogen
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human
Topics
  • Biomarkers, Tumor (metabolism)
  • Breast Neoplasms (enzymology, genetics, metabolism, pathology)
  • Class I Phosphatidylinositol 3-Kinases
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen (metabolism)
  • Metabolome
  • Microfluidics
  • Mutation (genetics)
  • Neoplasm Metastasis
  • Oligonucleotide Array Sequence Analysis
  • PTEN Phosphohydrolase (genetics)
  • Phosphatidylinositol 3-Kinases (genetics)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Receptors, Estrogen (metabolism)
  • Reproducibility of Results
  • Signal Transduction
  • Tumor Cells, Cultured

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