Diagnosis of Basal-Like Breast Cancer Using a FOXC1-Based Assay
Diagnosis of basal-like breast cancer (BLBC) remains a bottleneck to conducting effective clinical trials for this aggressive subtype. We postulated that elevated expression of Forkhead Box transcription factor C1 (FOXC1) is a simple and accurate diagnostic biomarker for BLBC. Accuracy of FOXC1 expr...
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| creator | Jensen, Tor W Ray, Tania Wang, Jinhua Li, Xiaodong Naritoku, Wesley Y Han, Bingchen Bellafiore, Frank Bagaria, Sanjay P Qu, Annie Cui, Xiaojiang Taylor, Clive R Ray, Partha S |
| description | Diagnosis of basal-like breast cancer (BLBC) remains a bottleneck to conducting effective clinical trials for this aggressive subtype. We postulated that elevated expression of Forkhead Box transcription factor C1 (FOXC1) is a simple and accurate diagnostic biomarker for BLBC.
Accuracy of FOXC1 expression in identifying BLBC was compared with the PAM50 gene expression panel in gene expression microarray (GEM) (n = 1992) and quantitative real-time polymerase chain reaction (qRT-PCR) (n = 349) datasets. A FOXC1-based immunohistochemical (IHC) assay was developed and assessed in 96 archival formalin-fixed, paraffin-embedded (FFPE) breast cancer samples that also underwent PAM50 profiling. All statistical tests were two-sided.
A FOXC1-based two-tier assay (IHC +/- qRT-PCR) accurately identified BLBC (AUC = 0.88) in an independent cohort of FFPE samples, validating the accuracy of FOXC1-defined BLBC in GEM (AUC = 0.90) and qRT-PCR (AUC = 0.88) studies, when compared with platform-specific PAM50-defined BLBC. The hazard ratio (HR) for disease-specific survival in patients having FOXC1-defined BLBC was 1.71 (95% CI = 1.31 to 2.23, P < .001), comparable to PAM50 assay-defined BLBC (HR = 1.74, 95% CI = 1.40 to 2.17, P < .001). FOXC1 expression also predicted the development of brain metastasis. Importantly, unlike triple-negative or Core Basal IHC definitions, a FOXC1-based definition is able to identify BLBC in both ER+ and HER2+ patients.
A FOXC1-based two-tier assay, by virtue of being rapid, simple, accurate, and cost-effective may emerge as the diagnostic assay of choice for BLBC. Such a test could substantially improve clinical trial enrichment of BLBC patients and accelerate the identification of effective chemotherapeutic options for this aggressive disease. |
| doi_str_mv | 10.1093/jnci/djv148 |
| format | Article |
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Accuracy of FOXC1 expression in identifying BLBC was compared with the PAM50 gene expression panel in gene expression microarray (GEM) (n = 1992) and quantitative real-time polymerase chain reaction (qRT-PCR) (n = 349) datasets. A FOXC1-based immunohistochemical (IHC) assay was developed and assessed in 96 archival formalin-fixed, paraffin-embedded (FFPE) breast cancer samples that also underwent PAM50 profiling. All statistical tests were two-sided.
A FOXC1-based two-tier assay (IHC +/- qRT-PCR) accurately identified BLBC (AUC = 0.88) in an independent cohort of FFPE samples, validating the accuracy of FOXC1-defined BLBC in GEM (AUC = 0.90) and qRT-PCR (AUC = 0.88) studies, when compared with platform-specific PAM50-defined BLBC. The hazard ratio (HR) for disease-specific survival in patients having FOXC1-defined BLBC was 1.71 (95% CI = 1.31 to 2.23, P < .001), comparable to PAM50 assay-defined BLBC (HR = 1.74, 95% CI = 1.40 to 2.17, P < .001). FOXC1 expression also predicted the development of brain metastasis. Importantly, unlike triple-negative or Core Basal IHC definitions, a FOXC1-based definition is able to identify BLBC in both ER+ and HER2+ patients.
A FOXC1-based two-tier assay, by virtue of being rapid, simple, accurate, and cost-effective may emerge as the diagnostic assay of choice for BLBC. Such a test could substantially improve clinical trial enrichment of BLBC patients and accelerate the identification of effective chemotherapeutic options for this aggressive disease.</description><identifier>ISSN: 0027-8874</identifier><identifier>EISSN: 1460-2105</identifier><identifier>DOI: 10.1093/jnci/djv148</identifier><identifier>PMID: 26041837</identifier><identifier>CODEN: JNCIEQ</identifier><language>eng</language><publisher>United States: Oxford Publishing Limited (England)</publisher><subject>Adult ; Aged ; Area Under Curve ; Biomarkers ; Biomarkers, Tumor - analysis ; Brain Neoplasms - chemistry ; Brain Neoplasms - diagnosis ; Brain Neoplasms - secondary ; Breast cancer ; Breast Neoplasms - chemistry ; Breast Neoplasms - diagnosis ; Breast Neoplasms - pathology ; Carcinoma, Basal Cell - chemistry ; Carcinoma, Basal Cell - diagnosis ; Chemotherapy ; Female ; Forkhead Transcription Factors - analysis ; Formaldehyde ; Gene expression ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Medical diagnosis ; Metastasis ; Middle Aged ; Paraffin Embedding ; Polymerase chain reaction ; Predictive Value of Tests ; Prognosis ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; ROC Curve ; Sensitivity and Specificity ; Tissue Fixation - methods ; Up-Regulation</subject><ispartof>JNCI : Journal of the National Cancer Institute, 2015-08, Vol.107 (8), p.1</ispartof><rights>The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.</rights><rights>Copyright Oxford Publishing Limited(England) Aug 2015</rights><rights>The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-40fffe20faeb3c21d034f0f04ffd2493fabb88bc06c0ce41a3432e75dc72f2893</citedby><cites>FETCH-LOGICAL-c409t-40fffe20faeb3c21d034f0f04ffd2493fabb88bc06c0ce41a3432e75dc72f2893</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26041837$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jensen, Tor W</creatorcontrib><creatorcontrib>Ray, Tania</creatorcontrib><creatorcontrib>Wang, Jinhua</creatorcontrib><creatorcontrib>Li, Xiaodong</creatorcontrib><creatorcontrib>Naritoku, Wesley Y</creatorcontrib><creatorcontrib>Han, Bingchen</creatorcontrib><creatorcontrib>Bellafiore, Frank</creatorcontrib><creatorcontrib>Bagaria, Sanjay P</creatorcontrib><creatorcontrib>Qu, Annie</creatorcontrib><creatorcontrib>Cui, Xiaojiang</creatorcontrib><creatorcontrib>Taylor, Clive R</creatorcontrib><creatorcontrib>Ray, Partha S</creatorcontrib><title>Diagnosis of Basal-Like Breast Cancer Using a FOXC1-Based Assay</title><title>JNCI : Journal of the National Cancer Institute</title><addtitle>J Natl Cancer Inst</addtitle><description>Diagnosis of basal-like breast cancer (BLBC) remains a bottleneck to conducting effective clinical trials for this aggressive subtype. We postulated that elevated expression of Forkhead Box transcription factor C1 (FOXC1) is a simple and accurate diagnostic biomarker for BLBC.
Accuracy of FOXC1 expression in identifying BLBC was compared with the PAM50 gene expression panel in gene expression microarray (GEM) (n = 1992) and quantitative real-time polymerase chain reaction (qRT-PCR) (n = 349) datasets. A FOXC1-based immunohistochemical (IHC) assay was developed and assessed in 96 archival formalin-fixed, paraffin-embedded (FFPE) breast cancer samples that also underwent PAM50 profiling. All statistical tests were two-sided.
A FOXC1-based two-tier assay (IHC +/- qRT-PCR) accurately identified BLBC (AUC = 0.88) in an independent cohort of FFPE samples, validating the accuracy of FOXC1-defined BLBC in GEM (AUC = 0.90) and qRT-PCR (AUC = 0.88) studies, when compared with platform-specific PAM50-defined BLBC. The hazard ratio (HR) for disease-specific survival in patients having FOXC1-defined BLBC was 1.71 (95% CI = 1.31 to 2.23, P < .001), comparable to PAM50 assay-defined BLBC (HR = 1.74, 95% CI = 1.40 to 2.17, P < .001). FOXC1 expression also predicted the development of brain metastasis. Importantly, unlike triple-negative or Core Basal IHC definitions, a FOXC1-based definition is able to identify BLBC in both ER+ and HER2+ patients.
A FOXC1-based two-tier assay, by virtue of being rapid, simple, accurate, and cost-effective may emerge as the diagnostic assay of choice for BLBC. Such a test could substantially improve clinical trial enrichment of BLBC patients and accelerate the identification of effective chemotherapeutic options for this aggressive disease.</description><subject>Adult</subject><subject>Aged</subject><subject>Area Under Curve</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Brain Neoplasms - chemistry</subject><subject>Brain Neoplasms - diagnosis</subject><subject>Brain Neoplasms - secondary</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - chemistry</subject><subject>Breast Neoplasms - diagnosis</subject><subject>Breast Neoplasms - pathology</subject><subject>Carcinoma, Basal Cell - chemistry</subject><subject>Carcinoma, Basal Cell - diagnosis</subject><subject>Chemotherapy</subject><subject>Female</subject><subject>Forkhead Transcription Factors - analysis</subject><subject>Formaldehyde</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Medical diagnosis</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Paraffin Embedding</subject><subject>Polymerase chain reaction</subject><subject>Predictive Value of Tests</subject><subject>Prognosis</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reproducibility of Results</subject><subject>ROC Curve</subject><subject>Sensitivity and Specificity</subject><subject>Tissue Fixation - methods</subject><subject>Up-Regulation</subject><issn>0027-8874</issn><issn>1460-2105</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1Lw0AQhhdRbK2evEvAiyCxsx9JNhelrVaFQi8WvC2bzW7dmCZ1tyn035vSWtS5zGEeXt7hQegSwx2GlPaLStl-Xqwx40eoi1kMIcEQHaMuAElCzhPWQWfeF9BOStgp6pAYGOY06aKHRyvnVe2tD2oTDKWXZTixnzoYOi39KhjJSmkXzLyt5oEMxtP3EQ5bTOfBwHu5OUcnRpZeX-x3D83GT2-jl3AyfX4dDSahYpCuQgbGGE3ASJ1RRXAOlBkwwIzJCUupkVnGeaYgVqA0w5IySnQS5SohhvCU9tD9LnfZZAudK12tnCzF0tmFdBtRSyv-Xir7Ieb1WrAoYjiN24CbfYCrvxrtV2JhvdJlKStdN17gmMdt1TjiLXr9Dy3qxlXtewInQCOecsJa6nZHKVd777Q5lMEgtmLEVozYiWnpq9_9D-yPCfoN1j6JZA</recordid><startdate>20150801</startdate><enddate>20150801</enddate><creator>Jensen, Tor W</creator><creator>Ray, Tania</creator><creator>Wang, Jinhua</creator><creator>Li, Xiaodong</creator><creator>Naritoku, Wesley Y</creator><creator>Han, Bingchen</creator><creator>Bellafiore, Frank</creator><creator>Bagaria, Sanjay P</creator><creator>Qu, Annie</creator><creator>Cui, Xiaojiang</creator><creator>Taylor, Clive R</creator><creator>Ray, Partha S</creator><general>Oxford Publishing Limited (England)</general><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150801</creationdate><title>Diagnosis of Basal-Like Breast Cancer Using a FOXC1-Based Assay</title><author>Jensen, Tor W ; Ray, Tania ; Wang, Jinhua ; Li, Xiaodong ; Naritoku, Wesley Y ; Han, Bingchen ; Bellafiore, Frank ; Bagaria, Sanjay P ; Qu, Annie ; Cui, Xiaojiang ; Taylor, Clive R ; Ray, Partha S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-40fffe20faeb3c21d034f0f04ffd2493fabb88bc06c0ce41a3432e75dc72f2893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Area Under Curve</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Brain Neoplasms - chemistry</topic><topic>Brain Neoplasms - diagnosis</topic><topic>Brain Neoplasms - secondary</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - chemistry</topic><topic>Breast Neoplasms - diagnosis</topic><topic>Breast Neoplasms - pathology</topic><topic>Carcinoma, Basal Cell - chemistry</topic><topic>Carcinoma, Basal Cell - diagnosis</topic><topic>Chemotherapy</topic><topic>Female</topic><topic>Forkhead Transcription Factors - analysis</topic><topic>Formaldehyde</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Medical diagnosis</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Paraffin Embedding</topic><topic>Polymerase chain reaction</topic><topic>Predictive Value of Tests</topic><topic>Prognosis</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Reproducibility of Results</topic><topic>ROC Curve</topic><topic>Sensitivity and Specificity</topic><topic>Tissue Fixation - methods</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jensen, Tor W</creatorcontrib><creatorcontrib>Ray, Tania</creatorcontrib><creatorcontrib>Wang, Jinhua</creatorcontrib><creatorcontrib>Li, Xiaodong</creatorcontrib><creatorcontrib>Naritoku, Wesley Y</creatorcontrib><creatorcontrib>Han, Bingchen</creatorcontrib><creatorcontrib>Bellafiore, Frank</creatorcontrib><creatorcontrib>Bagaria, Sanjay P</creatorcontrib><creatorcontrib>Qu, Annie</creatorcontrib><creatorcontrib>Cui, Xiaojiang</creatorcontrib><creatorcontrib>Taylor, Clive R</creatorcontrib><creatorcontrib>Ray, Partha S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>JNCI : Journal of the National Cancer Institute</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jensen, Tor W</au><au>Ray, Tania</au><au>Wang, Jinhua</au><au>Li, Xiaodong</au><au>Naritoku, Wesley Y</au><au>Han, Bingchen</au><au>Bellafiore, Frank</au><au>Bagaria, Sanjay P</au><au>Qu, Annie</au><au>Cui, Xiaojiang</au><au>Taylor, Clive R</au><au>Ray, Partha S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diagnosis of Basal-Like Breast Cancer Using a FOXC1-Based Assay</atitle><jtitle>JNCI : Journal of the National Cancer Institute</jtitle><addtitle>J Natl Cancer Inst</addtitle><date>2015-08-01</date><risdate>2015</risdate><volume>107</volume><issue>8</issue><spage>1</spage><pages>1-</pages><issn>0027-8874</issn><eissn>1460-2105</eissn><coden>JNCIEQ</coden><abstract>Diagnosis of basal-like breast cancer (BLBC) remains a bottleneck to conducting effective clinical trials for this aggressive subtype. We postulated that elevated expression of Forkhead Box transcription factor C1 (FOXC1) is a simple and accurate diagnostic biomarker for BLBC.
Accuracy of FOXC1 expression in identifying BLBC was compared with the PAM50 gene expression panel in gene expression microarray (GEM) (n = 1992) and quantitative real-time polymerase chain reaction (qRT-PCR) (n = 349) datasets. A FOXC1-based immunohistochemical (IHC) assay was developed and assessed in 96 archival formalin-fixed, paraffin-embedded (FFPE) breast cancer samples that also underwent PAM50 profiling. All statistical tests were two-sided.
A FOXC1-based two-tier assay (IHC +/- qRT-PCR) accurately identified BLBC (AUC = 0.88) in an independent cohort of FFPE samples, validating the accuracy of FOXC1-defined BLBC in GEM (AUC = 0.90) and qRT-PCR (AUC = 0.88) studies, when compared with platform-specific PAM50-defined BLBC. The hazard ratio (HR) for disease-specific survival in patients having FOXC1-defined BLBC was 1.71 (95% CI = 1.31 to 2.23, P < .001), comparable to PAM50 assay-defined BLBC (HR = 1.74, 95% CI = 1.40 to 2.17, P < .001). FOXC1 expression also predicted the development of brain metastasis. Importantly, unlike triple-negative or Core Basal IHC definitions, a FOXC1-based definition is able to identify BLBC in both ER+ and HER2+ patients.
A FOXC1-based two-tier assay, by virtue of being rapid, simple, accurate, and cost-effective may emerge as the diagnostic assay of choice for BLBC. Such a test could substantially improve clinical trial enrichment of BLBC patients and accelerate the identification of effective chemotherapeutic options for this aggressive disease.</abstract><cop>United States</cop><pub>Oxford Publishing Limited (England)</pub><pmid>26041837</pmid><doi>10.1093/jnci/djv148</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Area Under Curve Biomarkers Biomarkers, Tumor - analysis Brain Neoplasms - chemistry Brain Neoplasms - diagnosis Brain Neoplasms - secondary Breast cancer Breast Neoplasms - chemistry Breast Neoplasms - diagnosis Breast Neoplasms - pathology Carcinoma, Basal Cell - chemistry Carcinoma, Basal Cell - diagnosis Chemotherapy Female Forkhead Transcription Factors - analysis Formaldehyde Gene expression Gene Expression Regulation, Neoplastic Humans Immunohistochemistry Medical diagnosis Metastasis Middle Aged Paraffin Embedding Polymerase chain reaction Predictive Value of Tests Prognosis Real-Time Polymerase Chain Reaction Reproducibility of Results ROC Curve Sensitivity and Specificity Tissue Fixation - methods Up-Regulation |
| title | Diagnosis of Basal-Like Breast Cancer Using a FOXC1-Based Assay |
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