Tumour-infiltrating lymphocytes (TILs) and BRCA-like status in stage III breast cancer patients randomised to adjuvant intensified platinum-based chemotherapy versus conventional chemotherapy
The prognostic value of tumour-infiltrating lymphocytes (TILs) differs by breast cancer (BC) subtype. The aim of this study was to evaluate TILs in stage III BC in the context of BRCA1/2-like phenotypes and association with outcome and benefit of intensified platinum-based chemotherapy. Patients par...
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| Veröffentlicht in: | European journal of cancer (1990) 2020-03, Vol.127, p.240-250 |
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| creator | de Boo, Leonora Cimino-Mathews, Ashley Lubeck, Yoni Daletzakis, Antonios Opdam, Mark Sanders, Joyce Hooijberg, Erik van Rossum, Annelot Loncova, Zuzana Rieder, Dietmar Trajanoski, Zlatko Vollebergh, Marieke Sobral-Leite, Marcelo van de Vijver, Koen Broeks, Annegien van der Wiel, Rianne van Tinteren, Harm Linn, Sabine Horlings, Hugo Mark Kok, Marleen |
| description | The prognostic value of tumour-infiltrating lymphocytes (TILs) differs by breast cancer (BC) subtype. The aim of this study was to evaluate TILs in stage III BC in the context of BRCA1/2-like phenotypes and association with outcome and benefit of intensified platinum-based chemotherapy.
Patients participated in a randomised controlled trial of adjuvant intensified platinum-based chemotherapy versus conventional anthracycline-based chemotherapy carried out between 1993 and 1999 in stage III BC. Stromal TILs were scored according to International guidelines in these human epidermal growth factor receptor 2 (HER2)-negative tumours. BRCA-profiles were determined using Comparative Genomic Hybridization.
TIL levels were evaluated in 248 BCs. High TILs were associated with Triple Negative BC (TNBC). BRCA-like tumours harboured higher TILs compared to non-BRCA-like tumours (median TILs of 20% versus 10%, p |
| doi_str_mv | 10.1016/j.ejca.2019.12.003 |
| format | Article |
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Patients participated in a randomised controlled trial of adjuvant intensified platinum-based chemotherapy versus conventional anthracycline-based chemotherapy carried out between 1993 and 1999 in stage III BC. Stromal TILs were scored according to International guidelines in these human epidermal growth factor receptor 2 (HER2)-negative tumours. BRCA-profiles were determined using Comparative Genomic Hybridization.
TIL levels were evaluated in 248 BCs. High TILs were associated with Triple Negative BC (TNBC). BRCA-like tumours harboured higher TILs compared to non-BRCA-like tumours (median TILs of 20% versus 10%, p < 0.01). TIL levels in BRCA1-like tumours were higher compared to BRCA2-like tumours (median TILs of 20% versus 10%, p < 0.001). These correlations remained significant within the oestrogen (ER)-positive subgroup, however not within the TNBC subgroup. In this stage III BC cohort, high TIL level was associated with favourable outcome (TILs per 10% increment, recurrence-free survival (RFS): multivariate hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.71–0.94, p = 0.01; overall survival (OS): multivariate HR 0.80, 95% CI 0.68–0.94, p = 0.01). There was no significant interaction between TILs and benefit of intensified platinum-based chemotherapy.
In this high-risk breast cancer cohort, high TILs were associated with TNBC and BRCA1-like status. Within the ER-positive subgroup, TIL levels were higher in BRCA1-like compared to BRCA2-like tumours. When adjusted for clinical characteristics, TILs were significantly associated with a more favourable outcome in stage III BC patients.
•High TILs are significantly associated with TNBC and BRCA1-like breast tumours.•In TNBC, TIL levels are similar in BRCA-like versus non-BRCA-like tumours.•In ER-positive BCs, BRCA1-like tumours harbour more TILs compared to BRCA2-like tumours.•In stage III BC, high TILs are associated with a favourable outcome.•TILs are not associated with benefit of intensified platinum-based chemotherapy in this cohort.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2019.12.003</identifier><identifier>PMID: 31956037</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Anthracycline ; BRCA1 protein ; BRCA1 protein/genetics ; BRCA2 protein ; BRCA2 protein/genetics ; Breast cancer ; Carboplatin ; Chemotherapy ; Confidence intervals ; Epidermal growth factor ; ErbB-2 protein ; Estrogens ; Growth factors ; Health risks ; Homologous recombination deficiency ; Hybridization ; Lymphocytes ; Multivariate analysis ; Phenotypes ; Platinum ; Randomization ; Subgroups ; Survival ; Triple-negative breast neoplasms ; Tumors ; Tumour-infiltrating lymphocytes</subject><ispartof>European journal of cancer (1990), 2020-03, Vol.127, p.240-250</ispartof><rights>2019 Elsevier Ltd</rights><rights>Copyright © 2019 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Mar 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-7d0b5dd56c97258fcd906f07f28aec31f04288a346aee766866d49ebb8019f7e3</citedby><cites>FETCH-LOGICAL-c428t-7d0b5dd56c97258fcd906f07f28aec31f04288a346aee766866d49ebb8019f7e3</cites><orcidid>0000-0002-4626-8702</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejca.2019.12.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31956037$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Boo, Leonora</creatorcontrib><creatorcontrib>Cimino-Mathews, Ashley</creatorcontrib><creatorcontrib>Lubeck, Yoni</creatorcontrib><creatorcontrib>Daletzakis, Antonios</creatorcontrib><creatorcontrib>Opdam, Mark</creatorcontrib><creatorcontrib>Sanders, Joyce</creatorcontrib><creatorcontrib>Hooijberg, Erik</creatorcontrib><creatorcontrib>van Rossum, Annelot</creatorcontrib><creatorcontrib>Loncova, Zuzana</creatorcontrib><creatorcontrib>Rieder, Dietmar</creatorcontrib><creatorcontrib>Trajanoski, Zlatko</creatorcontrib><creatorcontrib>Vollebergh, Marieke</creatorcontrib><creatorcontrib>Sobral-Leite, Marcelo</creatorcontrib><creatorcontrib>van de Vijver, Koen</creatorcontrib><creatorcontrib>Broeks, Annegien</creatorcontrib><creatorcontrib>van der Wiel, Rianne</creatorcontrib><creatorcontrib>van Tinteren, Harm</creatorcontrib><creatorcontrib>Linn, Sabine</creatorcontrib><creatorcontrib>Horlings, Hugo Mark</creatorcontrib><creatorcontrib>Kok, Marleen</creatorcontrib><title>Tumour-infiltrating lymphocytes (TILs) and BRCA-like status in stage III breast cancer patients randomised to adjuvant intensified platinum-based chemotherapy versus conventional chemotherapy</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>The prognostic value of tumour-infiltrating lymphocytes (TILs) differs by breast cancer (BC) subtype. The aim of this study was to evaluate TILs in stage III BC in the context of BRCA1/2-like phenotypes and association with outcome and benefit of intensified platinum-based chemotherapy.
Patients participated in a randomised controlled trial of adjuvant intensified platinum-based chemotherapy versus conventional anthracycline-based chemotherapy carried out between 1993 and 1999 in stage III BC. Stromal TILs were scored according to International guidelines in these human epidermal growth factor receptor 2 (HER2)-negative tumours. BRCA-profiles were determined using Comparative Genomic Hybridization.
TIL levels were evaluated in 248 BCs. High TILs were associated with Triple Negative BC (TNBC). BRCA-like tumours harboured higher TILs compared to non-BRCA-like tumours (median TILs of 20% versus 10%, p < 0.01). TIL levels in BRCA1-like tumours were higher compared to BRCA2-like tumours (median TILs of 20% versus 10%, p < 0.001). These correlations remained significant within the oestrogen (ER)-positive subgroup, however not within the TNBC subgroup. In this stage III BC cohort, high TIL level was associated with favourable outcome (TILs per 10% increment, recurrence-free survival (RFS): multivariate hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.71–0.94, p = 0.01; overall survival (OS): multivariate HR 0.80, 95% CI 0.68–0.94, p = 0.01). There was no significant interaction between TILs and benefit of intensified platinum-based chemotherapy.
In this high-risk breast cancer cohort, high TILs were associated with TNBC and BRCA1-like status. Within the ER-positive subgroup, TIL levels were higher in BRCA1-like compared to BRCA2-like tumours. When adjusted for clinical characteristics, TILs were significantly associated with a more favourable outcome in stage III BC patients.
•High TILs are significantly associated with TNBC and BRCA1-like breast tumours.•In TNBC, TIL levels are similar in BRCA-like versus non-BRCA-like tumours.•In ER-positive BCs, BRCA1-like tumours harbour more TILs compared to BRCA2-like tumours.•In stage III BC, high TILs are associated with a favourable outcome.•TILs are not associated with benefit of intensified platinum-based chemotherapy in this cohort.</description><subject>Anthracycline</subject><subject>BRCA1 protein</subject><subject>BRCA1 protein/genetics</subject><subject>BRCA2 protein</subject><subject>BRCA2 protein/genetics</subject><subject>Breast cancer</subject><subject>Carboplatin</subject><subject>Chemotherapy</subject><subject>Confidence intervals</subject><subject>Epidermal growth factor</subject><subject>ErbB-2 protein</subject><subject>Estrogens</subject><subject>Growth factors</subject><subject>Health risks</subject><subject>Homologous recombination deficiency</subject><subject>Hybridization</subject><subject>Lymphocytes</subject><subject>Multivariate analysis</subject><subject>Phenotypes</subject><subject>Platinum</subject><subject>Randomization</subject><subject>Subgroups</subject><subject>Survival</subject><subject>Triple-negative breast neoplasms</subject><subject>Tumors</subject><subject>Tumour-infiltrating lymphocytes</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kVGL1DAUhYso7uzqH_BBAr6sD61J2qYp-LIOrg4MCDI-hzS53Ultk5qkA_Pr_GumzCrog08J4Tvn3pyTZa8ILggm7N1QwKBkQTFpC0ILjMsn2Ybwps0xr-nTbIPbus05rtqr7DqEAWPc8Ao_z65K0tYMl80m-3lYJrf43NjejNHLaOwDGs_TfHTqHCGg28NuH94iaTX68HV7l4_mO6AQZVwCMna9PQDa7Xao8yBDREpaBR7NyQlsDMgnpZtMAI2iQ1IPy0namKQRbDC9Se_zuI5dpryTK6aOMLl4BC_nMzqBD2mScvaU7IyzcvwLeJE96-UY4OXjeZN9u_942H7O918-7bZ3-1xVlMe80birta6Zahta817pFrMeNz3lElRJepwwLsuKSYCGMc6YrlroOp7C7Rsob7Lbi-_s3Y8FQhTpTwrGUVpwSxC0rGjJaFU3CX3zDzqkhNPiiapKQuuyZXWi6IVS3oXgoRezN5P0Z0GwWOsVg1jrFWu9glCR6k2i14_WSzeB_iP53WcC3l8ASFmcDHgRVOpBgTYeVBTamf_5_wK6Rrqj</recordid><startdate>202003</startdate><enddate>202003</enddate><creator>de Boo, Leonora</creator><creator>Cimino-Mathews, Ashley</creator><creator>Lubeck, Yoni</creator><creator>Daletzakis, Antonios</creator><creator>Opdam, Mark</creator><creator>Sanders, Joyce</creator><creator>Hooijberg, Erik</creator><creator>van Rossum, Annelot</creator><creator>Loncova, Zuzana</creator><creator>Rieder, Dietmar</creator><creator>Trajanoski, Zlatko</creator><creator>Vollebergh, Marieke</creator><creator>Sobral-Leite, Marcelo</creator><creator>van de Vijver, Koen</creator><creator>Broeks, Annegien</creator><creator>van der Wiel, Rianne</creator><creator>van Tinteren, Harm</creator><creator>Linn, Sabine</creator><creator>Horlings, Hugo Mark</creator><creator>Kok, Marleen</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4626-8702</orcidid></search><sort><creationdate>202003</creationdate><title>Tumour-infiltrating lymphocytes (TILs) and BRCA-like status in stage III breast cancer patients randomised to adjuvant intensified platinum-based chemotherapy versus conventional chemotherapy</title><author>de Boo, Leonora ; Cimino-Mathews, Ashley ; Lubeck, Yoni ; Daletzakis, Antonios ; Opdam, Mark ; Sanders, Joyce ; Hooijberg, Erik ; van Rossum, Annelot ; Loncova, Zuzana ; Rieder, Dietmar ; Trajanoski, Zlatko ; Vollebergh, Marieke ; Sobral-Leite, Marcelo ; van de Vijver, Koen ; Broeks, Annegien ; van der Wiel, Rianne ; van Tinteren, Harm ; Linn, Sabine ; Horlings, Hugo Mark ; Kok, Marleen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-7d0b5dd56c97258fcd906f07f28aec31f04288a346aee766866d49ebb8019f7e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Anthracycline</topic><topic>BRCA1 protein</topic><topic>BRCA1 protein/genetics</topic><topic>BRCA2 protein</topic><topic>BRCA2 protein/genetics</topic><topic>Breast cancer</topic><topic>Carboplatin</topic><topic>Chemotherapy</topic><topic>Confidence intervals</topic><topic>Epidermal growth factor</topic><topic>ErbB-2 protein</topic><topic>Estrogens</topic><topic>Growth factors</topic><topic>Health risks</topic><topic>Homologous recombination deficiency</topic><topic>Hybridization</topic><topic>Lymphocytes</topic><topic>Multivariate analysis</topic><topic>Phenotypes</topic><topic>Platinum</topic><topic>Randomization</topic><topic>Subgroups</topic><topic>Survival</topic><topic>Triple-negative breast neoplasms</topic><topic>Tumors</topic><topic>Tumour-infiltrating lymphocytes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Boo, Leonora</creatorcontrib><creatorcontrib>Cimino-Mathews, Ashley</creatorcontrib><creatorcontrib>Lubeck, Yoni</creatorcontrib><creatorcontrib>Daletzakis, Antonios</creatorcontrib><creatorcontrib>Opdam, Mark</creatorcontrib><creatorcontrib>Sanders, Joyce</creatorcontrib><creatorcontrib>Hooijberg, Erik</creatorcontrib><creatorcontrib>van Rossum, Annelot</creatorcontrib><creatorcontrib>Loncova, Zuzana</creatorcontrib><creatorcontrib>Rieder, Dietmar</creatorcontrib><creatorcontrib>Trajanoski, Zlatko</creatorcontrib><creatorcontrib>Vollebergh, Marieke</creatorcontrib><creatorcontrib>Sobral-Leite, Marcelo</creatorcontrib><creatorcontrib>van de Vijver, Koen</creatorcontrib><creatorcontrib>Broeks, Annegien</creatorcontrib><creatorcontrib>van der Wiel, Rianne</creatorcontrib><creatorcontrib>van Tinteren, Harm</creatorcontrib><creatorcontrib>Linn, Sabine</creatorcontrib><creatorcontrib>Horlings, Hugo Mark</creatorcontrib><creatorcontrib>Kok, Marleen</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology 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><jtitle>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Boo, Leonora</au><au>Cimino-Mathews, Ashley</au><au>Lubeck, Yoni</au><au>Daletzakis, Antonios</au><au>Opdam, Mark</au><au>Sanders, Joyce</au><au>Hooijberg, Erik</au><au>van Rossum, Annelot</au><au>Loncova, Zuzana</au><au>Rieder, Dietmar</au><au>Trajanoski, Zlatko</au><au>Vollebergh, Marieke</au><au>Sobral-Leite, Marcelo</au><au>van de Vijver, Koen</au><au>Broeks, Annegien</au><au>van der Wiel, Rianne</au><au>van Tinteren, Harm</au><au>Linn, Sabine</au><au>Horlings, Hugo Mark</au><au>Kok, Marleen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumour-infiltrating lymphocytes (TILs) and BRCA-like status in stage III breast cancer patients randomised to adjuvant intensified platinum-based chemotherapy versus conventional chemotherapy</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>2020-03</date><risdate>2020</risdate><volume>127</volume><spage>240</spage><epage>250</epage><pages>240-250</pages><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>The prognostic value of tumour-infiltrating lymphocytes (TILs) differs by breast cancer (BC) subtype. The aim of this study was to evaluate TILs in stage III BC in the context of BRCA1/2-like phenotypes and association with outcome and benefit of intensified platinum-based chemotherapy.
Patients participated in a randomised controlled trial of adjuvant intensified platinum-based chemotherapy versus conventional anthracycline-based chemotherapy carried out between 1993 and 1999 in stage III BC. Stromal TILs were scored according to International guidelines in these human epidermal growth factor receptor 2 (HER2)-negative tumours. BRCA-profiles were determined using Comparative Genomic Hybridization.
TIL levels were evaluated in 248 BCs. High TILs were associated with Triple Negative BC (TNBC). BRCA-like tumours harboured higher TILs compared to non-BRCA-like tumours (median TILs of 20% versus 10%, p < 0.01). TIL levels in BRCA1-like tumours were higher compared to BRCA2-like tumours (median TILs of 20% versus 10%, p < 0.001). These correlations remained significant within the oestrogen (ER)-positive subgroup, however not within the TNBC subgroup. In this stage III BC cohort, high TIL level was associated with favourable outcome (TILs per 10% increment, recurrence-free survival (RFS): multivariate hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.71–0.94, p = 0.01; overall survival (OS): multivariate HR 0.80, 95% CI 0.68–0.94, p = 0.01). There was no significant interaction between TILs and benefit of intensified platinum-based chemotherapy.
In this high-risk breast cancer cohort, high TILs were associated with TNBC and BRCA1-like status. Within the ER-positive subgroup, TIL levels were higher in BRCA1-like compared to BRCA2-like tumours. When adjusted for clinical characteristics, TILs were significantly associated with a more favourable outcome in stage III BC patients.
•High TILs are significantly associated with TNBC and BRCA1-like breast tumours.•In TNBC, TIL levels are similar in BRCA-like versus non-BRCA-like tumours.•In ER-positive BCs, BRCA1-like tumours harbour more TILs compared to BRCA2-like tumours.•In stage III BC, high TILs are associated with a favourable outcome.•TILs are not associated with benefit of intensified platinum-based chemotherapy in this cohort.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>31956037</pmid><doi>10.1016/j.ejca.2019.12.003</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-4626-8702</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0959-8049 |
| ispartof | European journal of cancer (1990), 2020-03, Vol.127, p.240-250 |
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| language | eng |
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| source | Elsevier ScienceDirect Journals Complete |
| subjects | Anthracycline BRCA1 protein BRCA1 protein/genetics BRCA2 protein BRCA2 protein/genetics Breast cancer Carboplatin Chemotherapy Confidence intervals Epidermal growth factor ErbB-2 protein Estrogens Growth factors Health risks Homologous recombination deficiency Hybridization Lymphocytes Multivariate analysis Phenotypes Platinum Randomization Subgroups Survival Triple-negative breast neoplasms Tumors Tumour-infiltrating lymphocytes |
| title | Tumour-infiltrating lymphocytes (TILs) and BRCA-like status in stage III breast cancer patients randomised to adjuvant intensified platinum-based chemotherapy versus conventional chemotherapy |
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