title: 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.
authors: Department of Oncology Biomarker Development, Genentech Inc., South San Francisco, California, United States of America.
authors: Erica B
authors: EB
authors: Schleifman
authors: Department of Oncology Biomarker Development, Genentech Inc., South San Francisco, California, United States of America.
authors: Rupal
authors: R
authors: Desai
authors: Department of Oncology Biomarker Development, Genentech Inc., South San Francisco, California, United States of America.
authors: Jill M
authors: JM
authors: Spoerke
authors: Department of Biostatistics, Genentech Inc., South San Francisco, California, United States of America.
authors: Yuanyuan
authors: Y
authors: Xiao
authors: Department of Oncology Biomarker Development, Genentech Inc., South San Francisco, California, United States of America.
authors: Cheryl
authors: C
authors: Wong
authors: Department of Oncology Biomarker Development, Genentech Inc., South San Francisco, California, United States of America.
authors: Ilma
authors: I
authors: Abbas
authors: Department of Oncology Biomarker Development, Genentech Inc., South San Francisco, California, United States of America.
authors: Carol
authors: C
authors: O'Brien
authors: Department of Oncology Biomarker Development, Genentech Inc., South San Francisco, California, United States of America.
authors: Rajesh
authors: R
authors: Patel
authors: Department of Oncology Biomarker Development, Genentech Inc., South San Francisco, California, United States of America.
authors: Teiko
authors: T
authors: Sumiyoshi
authors: Department of Oncology Biomarker Development, Genentech Inc., South San Francisco, California, United States of America.
authors: Ling
authors: L
authors: Fu
authors: Department of Oncology Biomarker Development, Genentech Inc., South San Francisco, California, United States of America.
authors: Rachel N
authors: RN
authors: Tam
authors: Department of Research Pathology, Genentech Inc., South San Francisco, California, United States of America.
authors: Hartmut
authors: H
authors: Koeppen
authors: Department of Oncology Biomarker Development, Genentech Inc., South San Francisco, California, United States of America.
authors: Timothy R
authors: TR
authors: Wilson
authors: Department of Oncology Biomarker Development, Genentech Inc., South San Francisco, California, United States of America.
authors: Rajiv
authors: R
authors: Raja
authors: Department of Oncology Biomarker Development, Genentech Inc., South San Francisco, California, United States of America.
authors: Garret M
authors: GM
authors: Hampton
authors: Department of Oncology Biomarker Development, Genentech Inc., South San Francisco, California, United States of America.
authors: Mark R
authors: MR
authors: Lackner
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D055442:Metabolome; D044085:Microfluidics; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D015203:Reproducibility of Results; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human