Targeted Biomarker Profiling of Matched Primary and Metastatic Estrogen Receptor Positive Breast Cancers
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{"title"=>"Targeted biomarker profiling of matched primary and metastatic estrogen receptor positive breast cancers", "type"=>"journal", "authors"=>[{"first_name"=>"Erica B.", "last_name"=>"Schleifman", "scopus_author_id"=>"16680398700"}, {"first_name"=>"Rupal", "last_name"=>"Desai", "scopus_author_id"=>"12806791900"}, {"first_name"=>"Jill M.", "last_name"=>"Spoerke", "scopus_author_id"=>"36769281000"}, {"first_name"=>"Yuanyuan", "last_name"=>"Xiao", "scopus_author_id"=>"56857011700"}, {"first_name"=>"Cheryl", "last_name"=>"Wong", "scopus_author_id"=>"57199121547"}, {"first_name"=>"Ilma", "last_name"=>"Abbas", "scopus_author_id"=>"56060215100"}, {"first_name"=>"Carol", "last_name"=>"O'Brien", "scopus_author_id"=>"7402419871"}, {"first_name"=>"Rajesh", "last_name"=>"Patel", "scopus_author_id"=>"55472426800"}, {"first_name"=>"Teiko", "last_name"=>"Sumiyoshi", "scopus_author_id"=>"56060024000"}, {"first_name"=>"Ling", "last_name"=>"Fu", "scopus_author_id"=>"35118930500"}, {"first_name"=>"Rachel N.", "last_name"=>"Tam", "scopus_author_id"=>"55532205100"}, {"first_name"=>"Hartmut", "last_name"=>"Koeppen", "scopus_author_id"=>"7003286723"}, {"first_name"=>"Timothy R.", "last_name"=>"Wilson", "scopus_author_id"=>"55490056900"}, {"first_name"=>"Rajiv", "last_name"=>"Raja", "scopus_author_id"=>"7102964792"}, {"first_name"=>"Garret M.", "last_name"=>"Hampton", "scopus_author_id"=>"7006693969"}, {"first_name"=>"Mark R.", "last_name"=>"Lackner", "scopus_author_id"=>"8350048700"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "isbn"=>"1932-6203", "pui"=>"372543847", "sgr"=>"84895765436", "doi"=>"10.1371/journal.pone.0088401", "scopus"=>"2-s2.0-84895765436", "pmid"=>"24520381"}, "id"=>"97067cdf-8eea-32d9-b604-e00329b289a6", "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.", "link"=>"http://www.mendeley.com/research/targeted-biomarker-profiling-matched-primary-metastatic-estrogen-receptor-positive-breast-cancers", "reader_count"=>42, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>15, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Student > Master"=>6, "Other"=>4, "Student > Bachelor"=>2, "Professor"=>1, "Student > Doctoral Student"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>15, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Student > Master"=>6, "Other"=>4, "Student > Bachelor"=>2, "Professor"=>1, "Student > Doctoral Student"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>14, "Mathematics"=>1, "Medicine and Dentistry"=>10, "Agricultural and Biological Sciences"=>11, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>14}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"United States"=>1, "United Kingdom"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1379559"], "description"=>"<p>(A) Schematic of the gene expression assay protocol. (B) Representative five-point standard curves of FFPE tumor RNA (red and black lines) and universal RNA (blue line) run on the breast cancer gene expression assay (slope of line indicated). (C) Intra-chip reproducibility of FFPE tumor samples run on the same 96.96 Dynamic Array. (D) Inter-chip reproducibility of the breast cancer gene expression assay assessed by comparing Ct values of universal RNA across seven independent assay runs. R-squared values are indicated in boxes.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "gene expression", "Genetic mutation", "Genetics of disease", "Molecular cell biology", "Nucleic acids", "rna", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Obstetrics and gynecology", "breast cancer", "oncology", "Cancers and neoplasms", "Breast tumors", "Benign breast tumors", "high-throughput", "microfluidic", "assay", "ffpe"], "article_id"=>928864, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Erica 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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088401.g003", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Development_of_a_high_throughput_microfluidic_gene_expression_assay_for_analysis_of_FFPE_breast_tumor_samples_/928864", "title"=>"Development of a high-throughput microfluidic gene expression assay for analysis of FFPE breast tumor samples.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-10 02:56:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/1379557"], "description"=>"<p>(A) Correlation between Ki67 staining levels determined by immunohistochemistry in matched primary and metastatic pairs (N = 71). The solid diagonal line (y = x) and the dashed lines (y = x±10, y = x±20) are shown to highlight the magnitude of the absolute differences between x and y axes. (B, C) Ki67 staining levels in primary (B) or metastatic (C) tumors with PI3K pathway alterations. The horizontal lines represent the mean Ki67staining level ± standard error.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "gene expression", "Genetic mutation", "Genetics of disease", "Molecular cell biology", "Nucleic acids", "rna", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Obstetrics and gynecology", "breast cancer", "oncology", "Cancers and neoplasms", "Breast tumors", "Benign breast tumors", "metastatic", "samples", "PI3K", "pathway"], "article_id"=>928862, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Erica 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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088401.g002", "stats"=>{"downloads"=>0, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ki67_status_in_primary_and_metastatic_samples_and_relationship_to_PI3K_pathway_activation_/928862", "title"=>"Ki67 status in primary and metastatic samples and relationship to PI3K pathway activation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-10 02:56:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/1379567"], "description"=>"<p>MND - Mutation not detected; E545X - E545A, G, D, K; Q546X - Q546E, K, R, L; Positive - PTEN positive, unable to determine H-Score; NA - Not available.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "gene expression", "Genetic mutation", "Genetics of disease", "Molecular cell biology", "Nucleic acids", "rna", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Obstetrics and gynecology", "breast cancer", "oncology", "Cancers and neoplasms", "Breast tumors", "Benign breast tumors", "pten", "Ki67", "77", "matched"], "article_id"=>928872, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Erica 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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088401.t001", "stats"=>{"downloads"=>13, "page_views"=>116, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PIK3CA_AKT1_PTEN_and_Ki67_status_across_a_collection_of_77_matched_ER_breast_cancers_/928872", "title"=>"PIK3CA, AKT1, PTEN and Ki67 status across a collection of 77 matched ER+ breast cancers.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-10 02:56:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/1379565"], "description"=>"<p>(A) Gene expression correlations between 61 matched primary and metastatic tumor samples for 90 genes from the breast cancer gene expression assay. Each dot represents the mean fold change between primary and metastatic samples for a single gene. (B) Correlation plots of genes that showed a greater than 1.5 fold difference in expression between matched primary and metastatic samples (FDR-adjusted P<0.05). Each dot represents the fold change between primary and metastatic samples for a single patient. The solid diagonal line (y = x) and the dashed lines (y = x±1) are shown to highlight the magnitude of the absolute differences between x and y axes.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "gene expression", "Genetic mutation", "Genetics of disease", "Molecular cell biology", "Nucleic acids", "rna", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Obstetrics and gynecology", "breast cancer", "oncology", "Cancers and neoplasms", "Breast tumors", "Benign breast tumors", "correlations", "matched", "metastatic", "cancer"], "article_id"=>928870, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Erica 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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088401.g006", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_expression_correlations_between_matched_primary_and_metastatic_ER_breast_cancer_tumor_samples_/928870", "title"=>"Gene expression correlations between matched primary and metastatic ER+ breast cancer tumor samples.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-10 02:56:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/1379576", "https://ndownloader.figshare.com/files/1379577", "https://ndownloader.figshare.com/files/1379578", "https://ndownloader.figshare.com/files/1379579", "https://ndownloader.figshare.com/files/1379580", "https://ndownloader.figshare.com/files/1379582"], "description"=>"<div><p>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 <i>PIK3CA</i> and <i>AKT1</i> 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.</p></div>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "gene expression", "Genetic mutation", "Genetics of disease", "Molecular cell biology", "Nucleic acids", "rna", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Obstetrics and gynecology", "breast cancer", "oncology", "Cancers and neoplasms", "Breast tumors", "Benign breast tumors", "biomarker", "profiling", "matched", "metastatic", "estrogen", "receptor"], "article_id"=>928881, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Erica 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"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0088401.s001", "https://dx.doi.org/10.1371/journal.pone.0088401.s002", "https://dx.doi.org/10.1371/journal.pone.0088401.s003", "https://dx.doi.org/10.1371/journal.pone.0088401.s004", "https://dx.doi.org/10.1371/journal.pone.0088401.s005", "https://dx.doi.org/10.1371/journal.pone.0088401.s006"], "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Targeted_Biomarker_Profiling_of_Matched_Primary_and_Metastatic_Estrogen_Receptor_Positive_Breast_Cancers_/928881", "title"=>"Targeted Biomarker Profiling of Matched Primary and Metastatic Estrogen Receptor Positive Breast Cancers", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-10 02:56:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/1379562"], "description"=>"<p>(A) Hierarchical clustering of thirty FFPE breast cancer tumor samples with known ER, PR and HER2 status run on the breast cancer gene expression assay. Blue =  triple negative, Pink  =  ER+, Yellow = HER2+ (red = high expression, green = low expression) (B) Box-plots indicating genes that showed statistically significant differential expression in the ER+ subtype, (C) ER+ and HER2+ subtype, (D) HER2+ subtype and (E) triple negative subtype samples (3N) (p-values indicated).</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "gene expression", "Genetic mutation", "Genetics of disease", "Molecular cell biology", "Nucleic acids", "rna", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Obstetrics and gynecology", "breast cancer", "oncology", "Cancers and neoplasms", "Breast tumors", "Benign breast tumors", "validation", "cancer", "assay", "samples", "immunohistochemical"], "article_id"=>928866, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Erica 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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088401.g004", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Biological_validation_of_the_breast_cancer_gene_expression_assay_using_samples_of_known_immunohistochemical_subtype_/928866", "title"=>"Biological validation of the breast cancer gene expression assay using samples of known immunohistochemical subtype.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-10 02:56:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/1379556"], "description"=>"<p>(A) Distribution of alterations in <i>PIK3CA</i>, <i>AKT1</i> and PTEN across 75 matched primary and metastatic ER+ breast cancers. PTEN null status denotes total absence of PTEN protein in neoplastic cells determined by immunohistochemistry. Arrows indicate patients with alterations in both <i>PIK3CA</i> and PTEN. (B) Frequency and overlap of PI3K pathway alterations in ER+ breast cancer samples. Biomarker frequencies calculated only from patients where tissue was evaluable for all biomarker assays. The data from the single <i>PIK3CA</i> exon 4 mutant sample was pooled with the exon 9 data, and the data from the exon 9/20 double mutant samples were pooled with exon 20 data. (C) Scatterplot of PTEN protein levels indicated by H-score in primary and metastatic samples. The solid diagonal line (y = x) and the dashed lines (y = x±50, y = x±100) are shown to highlight the magnitude of the absolute differences between x and y axes.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "gene expression", "Genetic mutation", "Genetics of disease", "Molecular cell biology", "Nucleic acids", "rna", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Obstetrics and gynecology", "breast cancer", "oncology", "Cancers and neoplasms", "Breast tumors", "Benign breast tumors", "pathway", "alterations", "metastatic"], "article_id"=>928861, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Erica 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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088401.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PI3K_pathway_alterations_in_primary_and_metastatic_ER_breast_cancers_/928861", "title"=>"PI3K pathway alterations in primary and metastatic ER+ breast cancers.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-10 02:56:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/1379563"], "description"=>"<p>(A) <i>MKI67</i> mRNA expression levels and relationship to Ki67 protein staining levels as determined by IHC. (B) Differentially expressed genes associated with Ki67 high or low protein staining levels (p-values indicated). Ki67 ≤ 15%, N = 16, Ki67 > 15%, N = 48.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "gene expression", "Genetic mutation", "Genetics of disease", "Molecular cell biology", "Nucleic acids", "rna", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Obstetrics and gynecology", "breast cancer", "oncology", "Cancers and neoplasms", "Breast tumors", "Benign breast tumors"], "article_id"=>928868, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Erica 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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088401.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ki67_protein_and_gene_expression_analysis_/928868", "title"=>"Ki67 protein and gene expression analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-10 02:56:41"}

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Relative Metric

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