Gene expression profiles of inflammatory breast cancer: correlation with response to neoadjuvant chemotherapy and metastasis-free survival
Inflammatory breast cancer (IBC) is an aggressive disease. To date, no molecular feature reliably predicts either the response to chemotherapy (CT) or the survival. Using DNA microarrays, we searched for multigene predictors. The World IBC Consortium generated whole-genome expression profiles of 137...
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| Veröffentlicht in: | Annals of oncology 2014-02, Vol.25 (2), p.358-365 |
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| creator | Bertucci, F. Ueno, N.T. Finetti, P. Vermeulen, P. Lucci, A. Robertson, F.M. Marsan, M. Iwamoto, T. Krishnamurthy, S. Masuda, H. Van Dam, P. Woodward, W.A. Cristofanilli, M. Reuben, J.M. Dirix, L. Viens, P. Symmans, W.F. Birnbaum, D. Van Laere, S.J. |
| description | Inflammatory breast cancer (IBC) is an aggressive disease. To date, no molecular feature reliably predicts either the response to chemotherapy (CT) or the survival. Using DNA microarrays, we searched for multigene predictors.
The World IBC Consortium generated whole-genome expression profiles of 137 IBC and 252 non-IBC (nIBC) samples. We searched for transcriptional profiles associated with pathological complete response (pCR) to neoadjuvant anthracycline-based CT and distant metastasis-free survival (DMFS) in respective subsets of 87 and 106 informative IBC samples. Correlations were investigated with predictive and prognostic gene expression signatures published in nIBC (nIBC-GES). Supervised analyses tested genes and activation signatures of 19 biological pathways and 234 transcription factors.
Three of five tested prognostic nIBC-GES and the two tested predictive nIBC-GES discriminated between IBC with and without pCR, as well as two interferon activation signatures. We identified a 107-gene signature enriched for immunity-related genes that distinguished between responders and nonresponders in IBC. Its robustness was demonstrated by external validation in three independent sets including two IBC sets and one nIBC set, with independent significant predictive value in IBC and nIBC validation sets in multivariate analysis. We found no robust signature associated with DMFS in patients with IBC, and neither of the tested prognostic GES, nor the molecular subtypes were informative, whereas they were in our nIBC series (220 stage I–III informative samples).
Despite the relatively small sample size, we show that response to neoadjuvant CT in IBC is, as in nIBC, associated with immunity-related processes, suggesting that similar mechanisms responsible for pCR exist. Analysis of a larger IBC series is warranted regarding the correlation of gene expression profiles and DMFS. |
| doi_str_mv | 10.1093/annonc/mdt496 |
| format | Article |
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The World IBC Consortium generated whole-genome expression profiles of 137 IBC and 252 non-IBC (nIBC) samples. We searched for transcriptional profiles associated with pathological complete response (pCR) to neoadjuvant anthracycline-based CT and distant metastasis-free survival (DMFS) in respective subsets of 87 and 106 informative IBC samples. Correlations were investigated with predictive and prognostic gene expression signatures published in nIBC (nIBC-GES). Supervised analyses tested genes and activation signatures of 19 biological pathways and 234 transcription factors.
Three of five tested prognostic nIBC-GES and the two tested predictive nIBC-GES discriminated between IBC with and without pCR, as well as two interferon activation signatures. We identified a 107-gene signature enriched for immunity-related genes that distinguished between responders and nonresponders in IBC. Its robustness was demonstrated by external validation in three independent sets including two IBC sets and one nIBC set, with independent significant predictive value in IBC and nIBC validation sets in multivariate analysis. We found no robust signature associated with DMFS in patients with IBC, and neither of the tested prognostic GES, nor the molecular subtypes were informative, whereas they were in our nIBC series (220 stage I–III informative samples).
Despite the relatively small sample size, we show that response to neoadjuvant CT in IBC is, as in nIBC, associated with immunity-related processes, suggesting that similar mechanisms responsible for pCR exist. Analysis of a larger IBC series is warranted regarding the correlation of gene expression profiles and DMFS.</description><identifier>ISSN: 0923-7534</identifier><identifier>EISSN: 1569-8041</identifier><identifier>DOI: 10.1093/annonc/mdt496</identifier><identifier>PMID: 24299959</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic agents ; Biological and medical sciences ; Carcinoma, Ductal, Breast - drug therapy ; Carcinoma, Ductal, Breast - metabolism ; Carcinoma, Ductal, Breast - mortality ; Carcinoma, Ductal, Breast - secondary ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Estrogen Receptor alpha - genetics ; Estrogen Receptor alpha - metabolism ; Female ; gene expression ; Gene Expression Profiling ; Gynecology. Andrology. Obstetrics ; Humans ; inflammatory breast cancer ; Inflammatory Breast Neoplasms - drug therapy ; Inflammatory Breast Neoplasms - metabolism ; Inflammatory Breast Neoplasms - mortality ; Inflammatory Breast Neoplasms - pathology ; Kaplan-Meier Estimate ; Mammary gland diseases ; Medical sciences ; Middle Aged ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Neoadjuvant Therapy ; Original ; Pharmacology. Drug treatments ; profiling ; prognosis ; Receptor, ErbB-2 - genetics ; Receptor, ErbB-2 - metabolism ; response to chemotherapy ; Transcriptome ; Tumors</subject><ispartof>Annals of oncology, 2014-02, Vol.25 (2), p.358-365</ispartof><rights>2014 European Society for Medical Oncology</rights><rights>2015 INIST-CNRS</rights><rights>The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c498t-ff7b4f89959a064c95aa19032399ce0268a9d2f2004e37276c6d1c37222776cc3</citedby><cites>FETCH-LOGICAL-c498t-ff7b4f89959a064c95aa19032399ce0268a9d2f2004e37276c6d1c37222776cc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28168497$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24299959$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bertucci, F.</creatorcontrib><creatorcontrib>Ueno, N.T.</creatorcontrib><creatorcontrib>Finetti, P.</creatorcontrib><creatorcontrib>Vermeulen, P.</creatorcontrib><creatorcontrib>Lucci, A.</creatorcontrib><creatorcontrib>Robertson, F.M.</creatorcontrib><creatorcontrib>Marsan, M.</creatorcontrib><creatorcontrib>Iwamoto, T.</creatorcontrib><creatorcontrib>Krishnamurthy, S.</creatorcontrib><creatorcontrib>Masuda, H.</creatorcontrib><creatorcontrib>Van Dam, P.</creatorcontrib><creatorcontrib>Woodward, W.A.</creatorcontrib><creatorcontrib>Cristofanilli, M.</creatorcontrib><creatorcontrib>Reuben, J.M.</creatorcontrib><creatorcontrib>Dirix, L.</creatorcontrib><creatorcontrib>Viens, P.</creatorcontrib><creatorcontrib>Symmans, W.F.</creatorcontrib><creatorcontrib>Birnbaum, D.</creatorcontrib><creatorcontrib>Van Laere, S.J.</creatorcontrib><title>Gene expression profiles of inflammatory breast cancer: correlation with response to neoadjuvant chemotherapy and metastasis-free survival</title><title>Annals of oncology</title><addtitle>Ann Oncol</addtitle><description>Inflammatory breast cancer (IBC) is an aggressive disease. To date, no molecular feature reliably predicts either the response to chemotherapy (CT) or the survival. Using DNA microarrays, we searched for multigene predictors.
The World IBC Consortium generated whole-genome expression profiles of 137 IBC and 252 non-IBC (nIBC) samples. We searched for transcriptional profiles associated with pathological complete response (pCR) to neoadjuvant anthracycline-based CT and distant metastasis-free survival (DMFS) in respective subsets of 87 and 106 informative IBC samples. Correlations were investigated with predictive and prognostic gene expression signatures published in nIBC (nIBC-GES). Supervised analyses tested genes and activation signatures of 19 biological pathways and 234 transcription factors.
Three of five tested prognostic nIBC-GES and the two tested predictive nIBC-GES discriminated between IBC with and without pCR, as well as two interferon activation signatures. We identified a 107-gene signature enriched for immunity-related genes that distinguished between responders and nonresponders in IBC. Its robustness was demonstrated by external validation in three independent sets including two IBC sets and one nIBC set, with independent significant predictive value in IBC and nIBC validation sets in multivariate analysis. We found no robust signature associated with DMFS in patients with IBC, and neither of the tested prognostic GES, nor the molecular subtypes were informative, whereas they were in our nIBC series (220 stage I–III informative samples).
Despite the relatively small sample size, we show that response to neoadjuvant CT in IBC is, as in nIBC, associated with immunity-related processes, suggesting that similar mechanisms responsible for pCR exist. Analysis of a larger IBC series is warranted regarding the correlation of gene expression profiles and DMFS.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Ductal, Breast - drug therapy</subject><subject>Carcinoma, Ductal, Breast - metabolism</subject><subject>Carcinoma, Ductal, Breast - mortality</subject><subject>Carcinoma, Ductal, Breast - secondary</subject><subject>Chemotherapy, Adjuvant</subject><subject>Disease-Free Survival</subject><subject>Estrogen Receptor alpha - genetics</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Female</subject><subject>gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>inflammatory breast cancer</subject><subject>Inflammatory Breast Neoplasms - drug therapy</subject><subject>Inflammatory Breast Neoplasms - metabolism</subject><subject>Inflammatory Breast Neoplasms - mortality</subject><subject>Inflammatory Breast Neoplasms - pathology</subject><subject>Kaplan-Meier Estimate</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Neoadjuvant Therapy</subject><subject>Original</subject><subject>Pharmacology. Drug treatments</subject><subject>profiling</subject><subject>prognosis</subject><subject>Receptor, ErbB-2 - genetics</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>response to chemotherapy</subject><subject>Transcriptome</subject><subject>Tumors</subject><issn>0923-7534</issn><issn>1569-8041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAURiMEotPCki3yBolNqOP8OJcFEqpoQarEBtbWHeeacZXYwfYE5hV4ajzKUGCBWNmWjz9916conlX8VcWhvkTnvNOX05Aa6B4Um6rtoOx5Uz0sNhxEXcq2bs6K8xjvOOcdCHhcnIlGAEALm-LHDTli9H0OFKP1js3BGztSZN4w68yI04TJhwPbBsKYmEanKbxm2odAI6bjm2827VgOmL2LxJJnjjwOd_sFXX6wo8mnHQWcDwzdwCZKOQijjaUJRCzuw2IXHJ8UjwyOkZ6e1ovi8_W7T1fvy9uPNx-u3t6WuoE-lcbIbWP6Y33kXaOhRayA16IG0MRF1yMMwgjOG6qlkJ3uhkrnnRAyH3R9UbxZc-f9dqJBk0sBRzUHO2E4KI9W_X3j7E598YuqgbdSQg54eQoI_uueYlKTjZrGEfPc-6iqLlcB0eVK_0UbqCXIivOMliuqg48xkLlvVHF1VK1W1WpVnfnnf45xT_9ym4EXJwCjxtGEbM7G31xfdX0DMnNy5Sh_-mIpqKgtZcuDDaSTGrz9R4Wf51bMOw</recordid><startdate>20140201</startdate><enddate>20140201</enddate><creator>Bertucci, F.</creator><creator>Ueno, N.T.</creator><creator>Finetti, P.</creator><creator>Vermeulen, P.</creator><creator>Lucci, A.</creator><creator>Robertson, F.M.</creator><creator>Marsan, M.</creator><creator>Iwamoto, T.</creator><creator>Krishnamurthy, S.</creator><creator>Masuda, H.</creator><creator>Van Dam, P.</creator><creator>Woodward, W.A.</creator><creator>Cristofanilli, M.</creator><creator>Reuben, J.M.</creator><creator>Dirix, L.</creator><creator>Viens, P.</creator><creator>Symmans, W.F.</creator><creator>Birnbaum, D.</creator><creator>Van Laere, S.J.</creator><general>Elsevier Ltd</general><general>Oxford University Press</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</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>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20140201</creationdate><title>Gene expression profiles of inflammatory breast cancer: correlation with response to neoadjuvant chemotherapy and metastasis-free survival</title><author>Bertucci, F. ; Ueno, N.T. ; Finetti, P. ; Vermeulen, P. ; Lucci, A. ; Robertson, F.M. ; Marsan, M. ; Iwamoto, T. ; Krishnamurthy, S. ; Masuda, H. ; Van Dam, P. ; Woodward, W.A. ; Cristofanilli, M. ; Reuben, J.M. ; Dirix, L. ; Viens, P. ; Symmans, W.F. ; Birnbaum, D. ; Van Laere, S.J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c498t-ff7b4f89959a064c95aa19032399ce0268a9d2f2004e37276c6d1c37222776cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Ductal, Breast - drug therapy</topic><topic>Carcinoma, Ductal, Breast - metabolism</topic><topic>Carcinoma, Ductal, Breast - mortality</topic><topic>Carcinoma, Ductal, Breast - secondary</topic><topic>Chemotherapy, Adjuvant</topic><topic>Disease-Free Survival</topic><topic>Estrogen Receptor alpha - genetics</topic><topic>Estrogen Receptor alpha - metabolism</topic><topic>Female</topic><topic>gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>inflammatory breast cancer</topic><topic>Inflammatory Breast Neoplasms - drug therapy</topic><topic>Inflammatory Breast Neoplasms - metabolism</topic><topic>Inflammatory Breast Neoplasms - mortality</topic><topic>Inflammatory Breast Neoplasms - pathology</topic><topic>Kaplan-Meier Estimate</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Neoadjuvant Therapy</topic><topic>Original</topic><topic>Pharmacology. Drug treatments</topic><topic>profiling</topic><topic>prognosis</topic><topic>Receptor, ErbB-2 - genetics</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>response to chemotherapy</topic><topic>Transcriptome</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bertucci, F.</creatorcontrib><creatorcontrib>Ueno, N.T.</creatorcontrib><creatorcontrib>Finetti, P.</creatorcontrib><creatorcontrib>Vermeulen, P.</creatorcontrib><creatorcontrib>Lucci, A.</creatorcontrib><creatorcontrib>Robertson, F.M.</creatorcontrib><creatorcontrib>Marsan, M.</creatorcontrib><creatorcontrib>Iwamoto, T.</creatorcontrib><creatorcontrib>Krishnamurthy, S.</creatorcontrib><creatorcontrib>Masuda, H.</creatorcontrib><creatorcontrib>Van Dam, P.</creatorcontrib><creatorcontrib>Woodward, W.A.</creatorcontrib><creatorcontrib>Cristofanilli, M.</creatorcontrib><creatorcontrib>Reuben, J.M.</creatorcontrib><creatorcontrib>Dirix, L.</creatorcontrib><creatorcontrib>Viens, P.</creatorcontrib><creatorcontrib>Symmans, W.F.</creatorcontrib><creatorcontrib>Birnbaum, D.</creatorcontrib><creatorcontrib>Van Laere, S.J.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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>Annals of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bertucci, F.</au><au>Ueno, N.T.</au><au>Finetti, P.</au><au>Vermeulen, P.</au><au>Lucci, A.</au><au>Robertson, F.M.</au><au>Marsan, M.</au><au>Iwamoto, T.</au><au>Krishnamurthy, S.</au><au>Masuda, H.</au><au>Van Dam, P.</au><au>Woodward, W.A.</au><au>Cristofanilli, M.</au><au>Reuben, J.M.</au><au>Dirix, L.</au><au>Viens, P.</au><au>Symmans, W.F.</au><au>Birnbaum, D.</au><au>Van Laere, S.J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gene expression profiles of inflammatory breast cancer: correlation with response to neoadjuvant chemotherapy and metastasis-free survival</atitle><jtitle>Annals of oncology</jtitle><addtitle>Ann Oncol</addtitle><date>2014-02-01</date><risdate>2014</risdate><volume>25</volume><issue>2</issue><spage>358</spage><epage>365</epage><pages>358-365</pages><issn>0923-7534</issn><eissn>1569-8041</eissn><abstract>Inflammatory breast cancer (IBC) is an aggressive disease. To date, no molecular feature reliably predicts either the response to chemotherapy (CT) or the survival. Using DNA microarrays, we searched for multigene predictors.
The World IBC Consortium generated whole-genome expression profiles of 137 IBC and 252 non-IBC (nIBC) samples. We searched for transcriptional profiles associated with pathological complete response (pCR) to neoadjuvant anthracycline-based CT and distant metastasis-free survival (DMFS) in respective subsets of 87 and 106 informative IBC samples. Correlations were investigated with predictive and prognostic gene expression signatures published in nIBC (nIBC-GES). Supervised analyses tested genes and activation signatures of 19 biological pathways and 234 transcription factors.
Three of five tested prognostic nIBC-GES and the two tested predictive nIBC-GES discriminated between IBC with and without pCR, as well as two interferon activation signatures. We identified a 107-gene signature enriched for immunity-related genes that distinguished between responders and nonresponders in IBC. Its robustness was demonstrated by external validation in three independent sets including two IBC sets and one nIBC set, with independent significant predictive value in IBC and nIBC validation sets in multivariate analysis. We found no robust signature associated with DMFS in patients with IBC, and neither of the tested prognostic GES, nor the molecular subtypes were informative, whereas they were in our nIBC series (220 stage I–III informative samples).
Despite the relatively small sample size, we show that response to neoadjuvant CT in IBC is, as in nIBC, associated with immunity-related processes, suggesting that similar mechanisms responsible for pCR exist. Analysis of a larger IBC series is warranted regarding the correlation of gene expression profiles and DMFS.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>24299959</pmid><doi>10.1093/annonc/mdt496</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Annals of oncology, 2014-02, Vol.25 (2), p.358-365 |
| issn | 0923-7534 1569-8041 |
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| subjects | Adult Aged Aged, 80 and over Antineoplastic agents Biological and medical sciences Carcinoma, Ductal, Breast - drug therapy Carcinoma, Ductal, Breast - metabolism Carcinoma, Ductal, Breast - mortality Carcinoma, Ductal, Breast - secondary Chemotherapy, Adjuvant Disease-Free Survival Estrogen Receptor alpha - genetics Estrogen Receptor alpha - metabolism Female gene expression Gene Expression Profiling Gynecology. Andrology. Obstetrics Humans inflammatory breast cancer Inflammatory Breast Neoplasms - drug therapy Inflammatory Breast Neoplasms - metabolism Inflammatory Breast Neoplasms - mortality Inflammatory Breast Neoplasms - pathology Kaplan-Meier Estimate Mammary gland diseases Medical sciences Middle Aged Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Neoadjuvant Therapy Original Pharmacology. Drug treatments profiling prognosis Receptor, ErbB-2 - genetics Receptor, ErbB-2 - metabolism response to chemotherapy Transcriptome Tumors |
| title | Gene expression profiles of inflammatory breast cancer: correlation with response to neoadjuvant chemotherapy and metastasis-free survival |
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