Deletion of chromosome 11q predicts response to anthracycline-based chemotherapy in early breast cancer
Despite the recent consensus on the eligibility of adjuvant systemic therapy in patients with lymph node-negative breast cancer (NNBC) based on clinicopathologic criteria, specific biological markers are needed to predict sensitivity to the different available therapeutic options. We examined the fe...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2007-01, Vol.67 (2), p.818-826 |
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| creator | CLIMENT, Joan DIMITROW, Peter FNDLYAND, Jane PALACIOS, Jose SIEBERT, Reiner ALBERTSON, Donna G GRAY, Joe W PINKEL, Daniel LLUCH, Ana MARTINEZ-CLIMENT, Jose A |
| description | Despite the recent consensus on the eligibility of adjuvant systemic therapy in patients with lymph node-negative breast cancer (NNBC) based on clinicopathologic criteria, specific biological markers are needed to predict sensitivity to the different available therapeutic options. We examined the feasibility of developing a genomic predictor of chemotherapy response and recurrence risk in 185 patients with NNBC using assembled arrays containing 2,460 bacterial artificial chromosome clones for scanning the genome for DNA copy number changes. After surgery, 90 patients received anthracycline-based chemotherapy, whereas 95 did not. Tamoxifen was administered to patients with hormone receptor-positive tumors. The association of genomic and clinicopathologic data and outcome was computed using Cox proportional hazard models and multiple testing adjustment procedures. Analysis of NNBC genomes revealed a common genomic signature. Specific DNA copy number aberrations were associated with hormonal receptor status, but not with other clinicopathologic variables. In patients treated with chemotherapy, none of the genomic changes were significantly correlated with recurrence. In patients not receiving chemotherapy, deletion of eight bacterial artificial chromosome clones clustered to chromosome 11q was independently associated with relapse (disease-free survival at 10 years+/-SE, 40%+/-14% versus 86%+/-6%; P |
| doi_str_mv | 10.1158/0008-5472.can-06-3307 |
| format | Article |
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We examined the feasibility of developing a genomic predictor of chemotherapy response and recurrence risk in 185 patients with NNBC using assembled arrays containing 2,460 bacterial artificial chromosome clones for scanning the genome for DNA copy number changes. After surgery, 90 patients received anthracycline-based chemotherapy, whereas 95 did not. Tamoxifen was administered to patients with hormone receptor-positive tumors. The association of genomic and clinicopathologic data and outcome was computed using Cox proportional hazard models and multiple testing adjustment procedures. Analysis of NNBC genomes revealed a common genomic signature. Specific DNA copy number aberrations were associated with hormonal receptor status, but not with other clinicopathologic variables. In patients treated with chemotherapy, none of the genomic changes were significantly correlated with recurrence. In patients not receiving chemotherapy, deletion of eight bacterial artificial chromosome clones clustered to chromosome 11q was independently associated with relapse (disease-free survival at 10 years+/-SE, 40%+/-14% versus 86%+/-6%; P<0.0001). The 54 patients with deletion of 11q (29%) did not present more aggressive clinicopathologic features than those without 11q loss. The adverse influence of 11q deletion on clinical outcome was confirmed in an independent validation series of 88 patients with NNBC. Our data suggests that patients with NNBC with the 11q deletion might benefit from anthracycline-based chemotherapy despite other clinical, pathologic, or genetic features. However, these initial findings should be evaluated in randomized clinical trials.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.can-06-3307</identifier><identifier>PMID: 17234794</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Anthracyclines - administration & dosage ; Antineoplastic agents ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Breast Neoplasms - drug therapy ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Chromosome Deletion ; Chromosomes, Human, Pair 11 ; Female ; Gene Dosage ; Genetic Predisposition to Disease ; Gynecology. Andrology. Obstetrics ; Humans ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Mammary gland diseases ; Medical sciences ; Middle Aged ; Neoplasm Recurrence, Local - genetics ; Nucleic Acid Hybridization ; Pharmacology. Drug treatments ; Predictive Value of Tests ; Receptors, Estrogen - biosynthesis ; Receptors, Progesterone - biosynthesis ; Tumors</subject><ispartof>Cancer research (Chicago, Ill.), 2007-01, Vol.67 (2), p.818-826</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-208ec88d1ece15420ab56b0dea8ca7e170bf071f405ce00068b639cc2c752c4c3</citedby><cites>FETCH-LOGICAL-c513t-208ec88d1ece15420ab56b0dea8ca7e170bf071f405ce00068b639cc2c752c4c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,3345,27907,27908</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18468880$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17234794$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CLIMENT, Joan</creatorcontrib><creatorcontrib>DIMITROW, Peter</creatorcontrib><creatorcontrib>FNDLYAND, Jane</creatorcontrib><creatorcontrib>PALACIOS, Jose</creatorcontrib><creatorcontrib>SIEBERT, Reiner</creatorcontrib><creatorcontrib>ALBERTSON, Donna G</creatorcontrib><creatorcontrib>GRAY, Joe W</creatorcontrib><creatorcontrib>PINKEL, Daniel</creatorcontrib><creatorcontrib>LLUCH, Ana</creatorcontrib><creatorcontrib>MARTINEZ-CLIMENT, Jose A</creatorcontrib><title>Deletion of chromosome 11q predicts response to anthracycline-based chemotherapy in early breast cancer</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>Despite the recent consensus on the eligibility of adjuvant systemic therapy in patients with lymph node-negative breast cancer (NNBC) based on clinicopathologic criteria, specific biological markers are needed to predict sensitivity to the different available therapeutic options. We examined the feasibility of developing a genomic predictor of chemotherapy response and recurrence risk in 185 patients with NNBC using assembled arrays containing 2,460 bacterial artificial chromosome clones for scanning the genome for DNA copy number changes. After surgery, 90 patients received anthracycline-based chemotherapy, whereas 95 did not. Tamoxifen was administered to patients with hormone receptor-positive tumors. The association of genomic and clinicopathologic data and outcome was computed using Cox proportional hazard models and multiple testing adjustment procedures. Analysis of NNBC genomes revealed a common genomic signature. Specific DNA copy number aberrations were associated with hormonal receptor status, but not with other clinicopathologic variables. In patients treated with chemotherapy, none of the genomic changes were significantly correlated with recurrence. In patients not receiving chemotherapy, deletion of eight bacterial artificial chromosome clones clustered to chromosome 11q was independently associated with relapse (disease-free survival at 10 years+/-SE, 40%+/-14% versus 86%+/-6%; P<0.0001). The 54 patients with deletion of 11q (29%) did not present more aggressive clinicopathologic features than those without 11q loss. The adverse influence of 11q deletion on clinical outcome was confirmed in an independent validation series of 88 patients with NNBC. Our data suggests that patients with NNBC with the 11q deletion might benefit from anthracycline-based chemotherapy despite other clinical, pathologic, or genetic features. However, these initial findings should be evaluated in randomized clinical trials.</description><subject>Adult</subject><subject>Anthracyclines - administration & dosage</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Chromosome Deletion</subject><subject>Chromosomes, Human, Pair 11</subject><subject>Female</subject><subject>Gene Dosage</subject><subject>Genetic Predisposition to Disease</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Lymphatic Metastasis</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>Nucleic Acid Hybridization</subject><subject>Pharmacology. Drug treatments</subject><subject>Predictive Value of Tests</subject><subject>Receptors, Estrogen - biosynthesis</subject><subject>Receptors, Progesterone - biosynthesis</subject><subject>Tumors</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctOwzAQRS0EgvL4BJA3sEsZO3bsLlF5Sgg2sLacyYQGJXGw00X_nlRUsGQ1GuncedzL2LmAuRDaXgOAzbQyco6-z6DI8hzMHpsJndvMKKX32eyXOWLHKX1OrRagD9mRMDJXZqFm7OOWWhqb0PNQc1zF0IUUOuJCfPEhUtXgmHikNIQ-ER8D9_24ih432DY9ZaVPVE066sK4ouiHDW96Tj62G15G8mnk03lI8ZQd1L5NdLarJ-z9_u5t-Zg9vz48LW-eM9QiHzMJltDaShCS0EqCL3VRQkXeojckDJQ1GFEr0EjTP4Uti3yBKNFoiQrzE3b1M3eI4WtNaXRdk5Da1vcU1skVdiGNFOpfUCy0ApAwgfoHxBhSilS7ITadjxsnwG2jcFub3dZmt7x5cVC4bRST7mK3YF12VP2pdt5PwOUO8Al9W8fJqCb9cVYV1lrIvwF9RZMS</recordid><startdate>20070115</startdate><enddate>20070115</enddate><creator>CLIMENT, Joan</creator><creator>DIMITROW, Peter</creator><creator>FNDLYAND, Jane</creator><creator>PALACIOS, Jose</creator><creator>SIEBERT, Reiner</creator><creator>ALBERTSON, Donna G</creator><creator>GRAY, Joe W</creator><creator>PINKEL, Daniel</creator><creator>LLUCH, Ana</creator><creator>MARTINEZ-CLIMENT, Jose A</creator><general>American Association for Cancer Research</general><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>7QL</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20070115</creationdate><title>Deletion of chromosome 11q predicts response to anthracycline-based chemotherapy in early breast cancer</title><author>CLIMENT, Joan ; DIMITROW, Peter ; FNDLYAND, Jane ; PALACIOS, Jose ; SIEBERT, Reiner ; ALBERTSON, Donna G ; GRAY, Joe W ; PINKEL, Daniel ; LLUCH, Ana ; MARTINEZ-CLIMENT, Jose A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-208ec88d1ece15420ab56b0dea8ca7e170bf071f405ce00068b639cc2c752c4c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adult</topic><topic>Anthracyclines - administration & dosage</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Chromosome Deletion</topic><topic>Chromosomes, Human, Pair 11</topic><topic>Female</topic><topic>Gene Dosage</topic><topic>Genetic Predisposition to Disease</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Lymphatic Metastasis</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasm Recurrence, Local - genetics</topic><topic>Nucleic Acid Hybridization</topic><topic>Pharmacology. 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We examined the feasibility of developing a genomic predictor of chemotherapy response and recurrence risk in 185 patients with NNBC using assembled arrays containing 2,460 bacterial artificial chromosome clones for scanning the genome for DNA copy number changes. After surgery, 90 patients received anthracycline-based chemotherapy, whereas 95 did not. Tamoxifen was administered to patients with hormone receptor-positive tumors. The association of genomic and clinicopathologic data and outcome was computed using Cox proportional hazard models and multiple testing adjustment procedures. Analysis of NNBC genomes revealed a common genomic signature. Specific DNA copy number aberrations were associated with hormonal receptor status, but not with other clinicopathologic variables. In patients treated with chemotherapy, none of the genomic changes were significantly correlated with recurrence. In patients not receiving chemotherapy, deletion of eight bacterial artificial chromosome clones clustered to chromosome 11q was independently associated with relapse (disease-free survival at 10 years+/-SE, 40%+/-14% versus 86%+/-6%; P<0.0001). The 54 patients with deletion of 11q (29%) did not present more aggressive clinicopathologic features than those without 11q loss. The adverse influence of 11q deletion on clinical outcome was confirmed in an independent validation series of 88 patients with NNBC. Our data suggests that patients with NNBC with the 11q deletion might benefit from anthracycline-based chemotherapy despite other clinical, pathologic, or genetic features. However, these initial findings should be evaluated in randomized clinical trials.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>17234794</pmid><doi>10.1158/0008-5472.can-06-3307</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Anthracyclines - administration & dosage Antineoplastic agents Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Breast Neoplasms - drug therapy Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Chromosome Deletion Chromosomes, Human, Pair 11 Female Gene Dosage Genetic Predisposition to Disease Gynecology. Andrology. Obstetrics Humans In Situ Hybridization, Fluorescence Lymphatic Metastasis Mammary gland diseases Medical sciences Middle Aged Neoplasm Recurrence, Local - genetics Nucleic Acid Hybridization Pharmacology. Drug treatments Predictive Value of Tests Receptors, Estrogen - biosynthesis Receptors, Progesterone - biosynthesis Tumors |
| title | Deletion of chromosome 11q predicts response to anthracycline-based chemotherapy in early breast cancer |
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