Loading…
Predicting early brain metastases based on clinicopathological factors and gene expression analysis in advanced HER2-positive breast cancer patients
The overexpression or amplification of the human epidermal growth factor receptor 2 gene ( HER2 / neu ) is associated with high risk of brain metastasis (BM). The identification of patients at highest immediate risk of BM could optimize screening and facilitate interventional trials. We performed ge...
Saved in:
| Published in: | Journal of neuro-oncology 2015-03, Vol.122 (1), p.205-216 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c573t-839eba66751425345e476d7556aef19fd259bb64dca3e3e860eae240a78de8713 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c573t-839eba66751425345e476d7556aef19fd259bb64dca3e3e860eae240a78de8713 |
| container_end_page | 216 |
| container_issue | 1 |
| container_start_page | 205 |
| container_title | Journal of neuro-oncology |
| container_volume | 122 |
| creator | Duchnowska, Renata Jassem, Jacek Goswami, Chirayu Pankaj Dundar, Murat Gökmen-Polar, Yesim Li, Lang Woditschka, Stephan Biernat, Wojciech Sosińska-Mielcarek, Katarzyna Czartoryska-Arłukowicz, Bogumiła Radecka, Barbara Tomasevic, Zorica Stępniak, Piotr Wojdan, Konrad Sledge, George W. Steeg, Patricia S. Badve, Sunil |
| description | The overexpression or amplification of the human epidermal growth factor receptor 2 gene (
HER2
/
neu
) is associated with high risk of brain metastasis (BM). The identification of patients at highest immediate risk of BM could optimize screening and facilitate interventional trials. We performed gene expression analysis using complementary deoxyribonucleic acid-mediated annealing, selection, extension and ligation and real-time quantitative reverse transcription PCR (qRT-PCR) in primary tumor samples from two independent cohorts of advanced HER2 positive breast cancer patients. Additionally, we analyzed predictive relevance of clinicopathological factors in this series. Study group included discovery Cohort A (84 patients) and validation Cohort B (75 patients). The only independent variables associated with the development of early BM in both cohorts were the visceral location of first distant relapse [Cohort A: hazard ratio (HR) 7.4, 95 % CI 2.4–22.3;
p
|
| doi_str_mv | 10.1007/s11060-014-1704-y |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4353882</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1668250046</sourcerecordid><originalsourceid>FETCH-LOGICAL-c573t-839eba66751425345e476d7556aef19fd259bb64dca3e3e860eae240a78de8713</originalsourceid><addsrcrecordid>eNqNks-KFDEQxoMo7rj6AF4k4MVLa9L5130RZFldYUERBW-hOl3dm6UnaZOewX4PH9iMsy6rIAghOdQv31dVfIQ85ewlZ8y8ypwzzSrGZcUNk9V6j2y4MqIywoj7ZMO4NpVq5dcT8ijna8aYNII_JCe1UqrVTbMhPz4m7L1bfBgpQppW2iXwgW5xgVwOZtqVu6cxUDf54F2cYbmKUxy9g4kO4JaYMoXQ0xEDUvw-J8zZFx4CTGv2mRY96PcQXNG5OP9UV3PMfvF7LGZYbKg71BItyh7Dkh-TBwNMGZ_cvKfky9vzz2cX1eWHd-_P3lxWrgy5VI1osQOtjeKyVkIqlEb3RikNOPB26GvVdp2WvQOBAhvNELCWDEzTY2O4OCWvj7rzrtti74p3gsnOyW8hrTaCt39Wgr-yY9xbKZRomroIvLgRSPHbDvNitz47nCYIGHfZcq2bWpW16_9BaymEUIe2nv-FXsddKsv8RXElpWpVofiRcinmnHC47Zsze4iHPcbDlnjYQzzsWv48uzvw7Y_feShAfQRyKYUR0x3rf6r-BLMbyX4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1661544595</pqid></control><display><type>article</type><title>Predicting early brain metastases based on clinicopathological factors and gene expression analysis in advanced HER2-positive breast cancer patients</title><source>Springer Nature</source><creator>Duchnowska, Renata ; Jassem, Jacek ; Goswami, Chirayu Pankaj ; Dundar, Murat ; Gökmen-Polar, Yesim ; Li, Lang ; Woditschka, Stephan ; Biernat, Wojciech ; Sosińska-Mielcarek, Katarzyna ; Czartoryska-Arłukowicz, Bogumiła ; Radecka, Barbara ; Tomasevic, Zorica ; Stępniak, Piotr ; Wojdan, Konrad ; Sledge, George W. ; Steeg, Patricia S. ; Badve, Sunil</creator><creatorcontrib>Duchnowska, Renata ; Jassem, Jacek ; Goswami, Chirayu Pankaj ; Dundar, Murat ; Gökmen-Polar, Yesim ; Li, Lang ; Woditschka, Stephan ; Biernat, Wojciech ; Sosińska-Mielcarek, Katarzyna ; Czartoryska-Arłukowicz, Bogumiła ; Radecka, Barbara ; Tomasevic, Zorica ; Stępniak, Piotr ; Wojdan, Konrad ; Sledge, George W. ; Steeg, Patricia S. ; Badve, Sunil</creatorcontrib><description>The overexpression or amplification of the human epidermal growth factor receptor 2 gene (
HER2
/
neu
) is associated with high risk of brain metastasis (BM). The identification of patients at highest immediate risk of BM could optimize screening and facilitate interventional trials. We performed gene expression analysis using complementary deoxyribonucleic acid-mediated annealing, selection, extension and ligation and real-time quantitative reverse transcription PCR (qRT-PCR) in primary tumor samples from two independent cohorts of advanced HER2 positive breast cancer patients. Additionally, we analyzed predictive relevance of clinicopathological factors in this series. Study group included discovery Cohort A (84 patients) and validation Cohort B (75 patients). The only independent variables associated with the development of early BM in both cohorts were the visceral location of first distant relapse [Cohort A: hazard ratio (HR) 7.4, 95 % CI 2.4–22.3;
p
< 0.001; Cohort B: HR 6.1, 95 % CI 1.5–25.6;
p
= 0.01] and the lack of trastuzumab administration in the metastatic setting (Cohort A: HR 5.0, 95 % CI 1.4–10.0;
p
= 0.009; Cohort B: HR 10.0, 95 % CI 2.0–100.0;
p
= 0.008). A profile including 13 genes was associated with early (≤36 months) symptomatic BM in the discovery cohort. This was refined by qRT-PCR to a 3-gene classifier (
RAD51
,
HDGF
,
TPR
) highly predictive of early BM (HR 5.3, 95 % CI 1.6–16.7;
p
= 0.005; multivariate analysis). However, predictive value of the classifier was not confirmed in the independent validation Cohort B. The presence of visceral metastases and the lack of trastuzumab administration in the metastatic setting apparently increase the likelihood of early BM in advanced HER2-positive breast cancer.</description><identifier>ISSN: 0167-594X</identifier><identifier>EISSN: 1573-7373</identifier><identifier>DOI: 10.1007/s11060-014-1704-y</identifier><identifier>PMID: 25559688</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Adult ; Aged ; Biomarkers, Tumor - genetics ; Brain Neoplasms - genetics ; Brain Neoplasms - mortality ; Brain Neoplasms - secondary ; Brain Neoplasms - therapy ; Breast Neoplasms - genetics ; Breast Neoplasms - mortality ; Breast Neoplasms - pathology ; Breast Neoplasms - therapy ; Carcinoma, Ductal, Breast - genetics ; Carcinoma, Ductal, Breast - mortality ; Carcinoma, Ductal, Breast - secondary ; Carcinoma, Ductal, Breast - therapy ; Carcinoma, Lobular - genetics ; Carcinoma, Lobular - mortality ; Carcinoma, Lobular - secondary ; Carcinoma, Lobular - therapy ; Clinical Study ; Cohort Studies ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Humans ; Medicine ; Medicine & Public Health ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Neurology ; Oligonucleotide Array Sequence Analysis ; Oncology ; Prognosis ; Real-Time Polymerase Chain Reaction ; Receptor, ErbB-2 - genetics ; Receptors, Estrogen - metabolism ; Receptors, Progesterone - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; Survival Rate</subject><ispartof>Journal of neuro-oncology, 2015-03, Vol.122 (1), p.205-216</ispartof><rights>The Author(s) 2015</rights><rights>Springer Science+Business Media New York 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c573t-839eba66751425345e476d7556aef19fd259bb64dca3e3e860eae240a78de8713</citedby><cites>FETCH-LOGICAL-c573t-839eba66751425345e476d7556aef19fd259bb64dca3e3e860eae240a78de8713</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/25559688$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Duchnowska, Renata</creatorcontrib><creatorcontrib>Jassem, Jacek</creatorcontrib><creatorcontrib>Goswami, Chirayu Pankaj</creatorcontrib><creatorcontrib>Dundar, Murat</creatorcontrib><creatorcontrib>Gökmen-Polar, Yesim</creatorcontrib><creatorcontrib>Li, Lang</creatorcontrib><creatorcontrib>Woditschka, Stephan</creatorcontrib><creatorcontrib>Biernat, Wojciech</creatorcontrib><creatorcontrib>Sosińska-Mielcarek, Katarzyna</creatorcontrib><creatorcontrib>Czartoryska-Arłukowicz, Bogumiła</creatorcontrib><creatorcontrib>Radecka, Barbara</creatorcontrib><creatorcontrib>Tomasevic, Zorica</creatorcontrib><creatorcontrib>Stępniak, Piotr</creatorcontrib><creatorcontrib>Wojdan, Konrad</creatorcontrib><creatorcontrib>Sledge, George W.</creatorcontrib><creatorcontrib>Steeg, Patricia S.</creatorcontrib><creatorcontrib>Badve, Sunil</creatorcontrib><title>Predicting early brain metastases based on clinicopathological factors and gene expression analysis in advanced HER2-positive breast cancer patients</title><title>Journal of neuro-oncology</title><addtitle>J Neurooncol</addtitle><addtitle>J Neurooncol</addtitle><description>The overexpression or amplification of the human epidermal growth factor receptor 2 gene (
HER2
/
neu
) is associated with high risk of brain metastasis (BM). The identification of patients at highest immediate risk of BM could optimize screening and facilitate interventional trials. We performed gene expression analysis using complementary deoxyribonucleic acid-mediated annealing, selection, extension and ligation and real-time quantitative reverse transcription PCR (qRT-PCR) in primary tumor samples from two independent cohorts of advanced HER2 positive breast cancer patients. Additionally, we analyzed predictive relevance of clinicopathological factors in this series. Study group included discovery Cohort A (84 patients) and validation Cohort B (75 patients). The only independent variables associated with the development of early BM in both cohorts were the visceral location of first distant relapse [Cohort A: hazard ratio (HR) 7.4, 95 % CI 2.4–22.3;
p
< 0.001; Cohort B: HR 6.1, 95 % CI 1.5–25.6;
p
= 0.01] and the lack of trastuzumab administration in the metastatic setting (Cohort A: HR 5.0, 95 % CI 1.4–10.0;
p
= 0.009; Cohort B: HR 10.0, 95 % CI 2.0–100.0;
p
= 0.008). A profile including 13 genes was associated with early (≤36 months) symptomatic BM in the discovery cohort. This was refined by qRT-PCR to a 3-gene classifier (
RAD51
,
HDGF
,
TPR
) highly predictive of early BM (HR 5.3, 95 % CI 1.6–16.7;
p
= 0.005; multivariate analysis). However, predictive value of the classifier was not confirmed in the independent validation Cohort B. The presence of visceral metastases and the lack of trastuzumab administration in the metastatic setting apparently increase the likelihood of early BM in advanced HER2-positive breast cancer.</description><subject>Adult</subject><subject>Aged</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - mortality</subject><subject>Brain Neoplasms - secondary</subject><subject>Brain Neoplasms - therapy</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - mortality</subject><subject>Breast Neoplasms - pathology</subject><subject>Breast Neoplasms - therapy</subject><subject>Carcinoma, Ductal, Breast - genetics</subject><subject>Carcinoma, Ductal, Breast - mortality</subject><subject>Carcinoma, Ductal, Breast - secondary</subject><subject>Carcinoma, Ductal, Breast - therapy</subject><subject>Carcinoma, Lobular - genetics</subject><subject>Carcinoma, Lobular - mortality</subject><subject>Carcinoma, Lobular - secondary</subject><subject>Carcinoma, Lobular - therapy</subject><subject>Clinical Study</subject><subject>Cohort Studies</subject><subject>Combined Modality Therapy</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gene Expression Profiling</subject><subject>Humans</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Staging</subject><subject>Neurology</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Oncology</subject><subject>Prognosis</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptor, ErbB-2 - genetics</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Receptors, Progesterone - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>Survival Rate</subject><issn>0167-594X</issn><issn>1573-7373</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqNks-KFDEQxoMo7rj6AF4k4MVLa9L5130RZFldYUERBW-hOl3dm6UnaZOewX4PH9iMsy6rIAghOdQv31dVfIQ85ewlZ8y8ypwzzSrGZcUNk9V6j2y4MqIywoj7ZMO4NpVq5dcT8ijna8aYNII_JCe1UqrVTbMhPz4m7L1bfBgpQppW2iXwgW5xgVwOZtqVu6cxUDf54F2cYbmKUxy9g4kO4JaYMoXQ0xEDUvw-J8zZFx4CTGv2mRY96PcQXNG5OP9UV3PMfvF7LGZYbKg71BItyh7Dkh-TBwNMGZ_cvKfky9vzz2cX1eWHd-_P3lxWrgy5VI1osQOtjeKyVkIqlEb3RikNOPB26GvVdp2WvQOBAhvNELCWDEzTY2O4OCWvj7rzrtti74p3gsnOyW8hrTaCt39Wgr-yY9xbKZRomroIvLgRSPHbDvNitz47nCYIGHfZcq2bWpW16_9BaymEUIe2nv-FXsddKsv8RXElpWpVofiRcinmnHC47Zsze4iHPcbDlnjYQzzsWv48uzvw7Y_feShAfQRyKYUR0x3rf6r-BLMbyX4</recordid><startdate>20150301</startdate><enddate>20150301</enddate><creator>Duchnowska, Renata</creator><creator>Jassem, Jacek</creator><creator>Goswami, Chirayu Pankaj</creator><creator>Dundar, Murat</creator><creator>Gökmen-Polar, Yesim</creator><creator>Li, Lang</creator><creator>Woditschka, Stephan</creator><creator>Biernat, Wojciech</creator><creator>Sosińska-Mielcarek, Katarzyna</creator><creator>Czartoryska-Arłukowicz, Bogumiła</creator><creator>Radecka, Barbara</creator><creator>Tomasevic, Zorica</creator><creator>Stępniak, Piotr</creator><creator>Wojdan, Konrad</creator><creator>Sledge, George W.</creator><creator>Steeg, Patricia S.</creator><creator>Badve, Sunil</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>C6C</scope><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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20150301</creationdate><title>Predicting early brain metastases based on clinicopathological factors and gene expression analysis in advanced HER2-positive breast cancer patients</title><author>Duchnowska, Renata ; Jassem, Jacek ; Goswami, Chirayu Pankaj ; Dundar, Murat ; Gökmen-Polar, Yesim ; Li, Lang ; Woditschka, Stephan ; Biernat, Wojciech ; Sosińska-Mielcarek, Katarzyna ; Czartoryska-Arłukowicz, Bogumiła ; Radecka, Barbara ; Tomasevic, Zorica ; Stępniak, Piotr ; Wojdan, Konrad ; Sledge, George W. ; Steeg, Patricia S. ; Badve, Sunil</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c573t-839eba66751425345e476d7556aef19fd259bb64dca3e3e860eae240a78de8713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - mortality</topic><topic>Brain Neoplasms - secondary</topic><topic>Brain Neoplasms - therapy</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - mortality</topic><topic>Breast Neoplasms - pathology</topic><topic>Breast Neoplasms - therapy</topic><topic>Carcinoma, Ductal, Breast - genetics</topic><topic>Carcinoma, Ductal, Breast - mortality</topic><topic>Carcinoma, Ductal, Breast - secondary</topic><topic>Carcinoma, Ductal, Breast - therapy</topic><topic>Carcinoma, Lobular - genetics</topic><topic>Carcinoma, Lobular - mortality</topic><topic>Carcinoma, Lobular - secondary</topic><topic>Carcinoma, Lobular - therapy</topic><topic>Clinical Study</topic><topic>Cohort Studies</topic><topic>Combined Modality Therapy</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gene Expression Profiling</topic><topic>Humans</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Neoplasm Grading</topic><topic>Neoplasm Staging</topic><topic>Neurology</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Oncology</topic><topic>Prognosis</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Receptor, ErbB-2 - genetics</topic><topic>Receptors, Estrogen - metabolism</topic><topic>Receptors, Progesterone - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>Survival Rate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Duchnowska, Renata</creatorcontrib><creatorcontrib>Jassem, Jacek</creatorcontrib><creatorcontrib>Goswami, Chirayu Pankaj</creatorcontrib><creatorcontrib>Dundar, Murat</creatorcontrib><creatorcontrib>Gökmen-Polar, Yesim</creatorcontrib><creatorcontrib>Li, Lang</creatorcontrib><creatorcontrib>Woditschka, Stephan</creatorcontrib><creatorcontrib>Biernat, Wojciech</creatorcontrib><creatorcontrib>Sosińska-Mielcarek, Katarzyna</creatorcontrib><creatorcontrib>Czartoryska-Arłukowicz, Bogumiła</creatorcontrib><creatorcontrib>Radecka, Barbara</creatorcontrib><creatorcontrib>Tomasevic, Zorica</creatorcontrib><creatorcontrib>Stępniak, Piotr</creatorcontrib><creatorcontrib>Wojdan, Konrad</creatorcontrib><creatorcontrib>Sledge, George W.</creatorcontrib><creatorcontrib>Steeg, Patricia S.</creatorcontrib><creatorcontrib>Badve, Sunil</creatorcontrib><collection>Springer Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of neuro-oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Duchnowska, Renata</au><au>Jassem, Jacek</au><au>Goswami, Chirayu Pankaj</au><au>Dundar, Murat</au><au>Gökmen-Polar, Yesim</au><au>Li, Lang</au><au>Woditschka, Stephan</au><au>Biernat, Wojciech</au><au>Sosińska-Mielcarek, Katarzyna</au><au>Czartoryska-Arłukowicz, Bogumiła</au><au>Radecka, Barbara</au><au>Tomasevic, Zorica</au><au>Stępniak, Piotr</au><au>Wojdan, Konrad</au><au>Sledge, George W.</au><au>Steeg, Patricia S.</au><au>Badve, Sunil</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Predicting early brain metastases based on clinicopathological factors and gene expression analysis in advanced HER2-positive breast cancer patients</atitle><jtitle>Journal of neuro-oncology</jtitle><stitle>J Neurooncol</stitle><addtitle>J Neurooncol</addtitle><date>2015-03-01</date><risdate>2015</risdate><volume>122</volume><issue>1</issue><spage>205</spage><epage>216</epage><pages>205-216</pages><issn>0167-594X</issn><eissn>1573-7373</eissn><abstract>The overexpression or amplification of the human epidermal growth factor receptor 2 gene (
HER2
/
neu
) is associated with high risk of brain metastasis (BM). The identification of patients at highest immediate risk of BM could optimize screening and facilitate interventional trials. We performed gene expression analysis using complementary deoxyribonucleic acid-mediated annealing, selection, extension and ligation and real-time quantitative reverse transcription PCR (qRT-PCR) in primary tumor samples from two independent cohorts of advanced HER2 positive breast cancer patients. Additionally, we analyzed predictive relevance of clinicopathological factors in this series. Study group included discovery Cohort A (84 patients) and validation Cohort B (75 patients). The only independent variables associated with the development of early BM in both cohorts were the visceral location of first distant relapse [Cohort A: hazard ratio (HR) 7.4, 95 % CI 2.4–22.3;
p
< 0.001; Cohort B: HR 6.1, 95 % CI 1.5–25.6;
p
= 0.01] and the lack of trastuzumab administration in the metastatic setting (Cohort A: HR 5.0, 95 % CI 1.4–10.0;
p
= 0.009; Cohort B: HR 10.0, 95 % CI 2.0–100.0;
p
= 0.008). A profile including 13 genes was associated with early (≤36 months) symptomatic BM in the discovery cohort. This was refined by qRT-PCR to a 3-gene classifier (
RAD51
,
HDGF
,
TPR
) highly predictive of early BM (HR 5.3, 95 % CI 1.6–16.7;
p
= 0.005; multivariate analysis). However, predictive value of the classifier was not confirmed in the independent validation Cohort B. The presence of visceral metastases and the lack of trastuzumab administration in the metastatic setting apparently increase the likelihood of early BM in advanced HER2-positive breast cancer.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>25559688</pmid><doi>10.1007/s11060-014-1704-y</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-594X |
| ispartof | Journal of neuro-oncology, 2015-03, Vol.122 (1), p.205-216 |
| issn | 0167-594X 1573-7373 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4353882 |
| source | Springer Nature |
| subjects | Adult Aged Biomarkers, Tumor - genetics Brain Neoplasms - genetics Brain Neoplasms - mortality Brain Neoplasms - secondary Brain Neoplasms - therapy Breast Neoplasms - genetics Breast Neoplasms - mortality Breast Neoplasms - pathology Breast Neoplasms - therapy Carcinoma, Ductal, Breast - genetics Carcinoma, Ductal, Breast - mortality Carcinoma, Ductal, Breast - secondary Carcinoma, Ductal, Breast - therapy Carcinoma, Lobular - genetics Carcinoma, Lobular - mortality Carcinoma, Lobular - secondary Carcinoma, Lobular - therapy Clinical Study Cohort Studies Combined Modality Therapy Female Follow-Up Studies Gene Expression Profiling Humans Medicine Medicine & Public Health Middle Aged Neoplasm Grading Neoplasm Staging Neurology Oligonucleotide Array Sequence Analysis Oncology Prognosis Real-Time Polymerase Chain Reaction Receptor, ErbB-2 - genetics Receptors, Estrogen - metabolism Receptors, Progesterone - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics Survival Rate |
| title | Predicting early brain metastases based on clinicopathological factors and gene expression analysis in advanced HER2-positive breast cancer patients |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-14T23%3A21%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Predicting%20early%20brain%20metastases%20based%20on%20clinicopathological%20factors%20and%20gene%20expression%20analysis%20in%20advanced%20HER2-positive%20breast%20cancer%20patients&rft.jtitle=Journal%20of%20neuro-oncology&rft.au=Duchnowska,%20Renata&rft.date=2015-03-01&rft.volume=122&rft.issue=1&rft.spage=205&rft.epage=216&rft.pages=205-216&rft.issn=0167-594X&rft.eissn=1573-7373&rft_id=info:doi/10.1007/s11060-014-1704-y&rft_dat=%3Cproquest_pubme%3E1668250046%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c573t-839eba66751425345e476d7556aef19fd259bb64dca3e3e860eae240a78de8713%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1661544595&rft_id=info:pmid/25559688&rfr_iscdi=true |