The prevalence and clinical relevance of tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ of the breast
Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct in invasive breast cancer, but their clinical role in ductal carcinoma in situ (DCIS) has not been ascertained. We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women w...
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| Veröffentlicht in: | Annals of oncology 2017-02, Vol.28 (2), p.321-328 |
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| creator | Pruneri, G. Lazzeroni, M. Bagnardi, V. Tiburzio, G.B. Rotmensz, N. DeCensi, A. Guerrieri-Gonzaga, A. Vingiani, A. Curigliano, G. Zurrida, S. Bassi, F. Salgado, R. Van den Eynden, G. Loi, S. Denkert, C. Bonanni, B. Viale, G. |
| description | Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct in invasive breast cancer, but their clinical role in ductal carcinoma in situ (DCIS) has not been ascertained.
We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women with a median follow-up of 8.2years. Detailed criteria for TILs evaluation were pre-defined involving the International Immuno-Oncology Biomarker Working Group. TILs percentage was considered both as a continuous and categorical variable. Levels of TILs were examined for their associations with ipsilateral breast event (IBE), whether in situ or invasive.
Of the 1488 patients with DCIS under study, 35.1% had |
| doi_str_mv | 10.1093/annonc/mdw623 |
| format | Article |
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We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women with a median follow-up of 8.2years. Detailed criteria for TILs evaluation were pre-defined involving the International Immuno-Oncology Biomarker Working Group. TILs percentage was considered both as a continuous and categorical variable. Levels of TILs were examined for their associations with ipsilateral breast event (IBE), whether in situ or invasive.
Of the 1488 patients with DCIS under study, 35.1% had <1%, 58.3% 1–49% and 6.5% ≥50% peri-ductal stromal lymphocytes. The interobserver agreement in TILs evaluation, measured by the intraclass correlation coefficient (ICC) was 0.96 (95% CI 0.95–0.97). At univariable analysis, clinical factors significantly associated with TILs (P ≤0.001) were intrinsic subtype, grade, necrosis, type of surgery. Her-2 positive DCIS were more frequently associated with TILs (24% of patients with TILs ≥50%), followed by the triple negative (11%), Luminal B/Her-2 positive (9%) and Luminal A/B subtypes (1%) (P < 0.0001). We did not find any association between TILs as a continuous variable and the risk of IBEs. Likewise, when patients were stratified by TILs percentage (<1%, between 1% and 49.9%, and ≥50%), no statistically significant association was observed (10-year cumulative incidence of IBEs: 19%, 17.3%, and 18.7% respectively, P = 0.767).
TILs occur more frequently in the Her-2 positive DCIS. Although we did not find a significant association between TILs and the 10-year risk of IBE, our data suggest that immunotherapies might be considered in subsets of DCIS patients.</description><identifier>ISSN: 0923-7534</identifier><identifier>EISSN: 1569-8041</identifier><identifier>DOI: 10.1093/annonc/mdw623</identifier><identifier>PMID: 28426105</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Aged ; Breast Neoplasms - epidemiology ; Breast Neoplasms - immunology ; Breast Neoplasms - pathology ; Breast Neoplasms - therapy ; Carcinoma, Intraductal, Noninfiltrating - epidemiology ; Carcinoma, Intraductal, Noninfiltrating - immunology ; Carcinoma, Intraductal, Noninfiltrating - pathology ; Carcinoma, Intraductal, Noninfiltrating - therapy ; ductal carcinoma in situ ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating - pathology ; Middle Aged ; Neoplasm Recurrence, Local - epidemiology ; Neoplasm Recurrence, Local - immunology ; Neoplasm Recurrence, Local - prevention & control ; Prevalence ; Prognosis ; Proportional Hazards Models ; tumor infiltrating lymphocytes</subject><ispartof>Annals of oncology, 2017-02, Vol.28 (2), p.321-328</ispartof><rights>2016 European Society for Medical Oncology</rights><rights>The Author 2016. 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.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c380t-d176d6d24b90a877e1c12ebe156f48742d90033f4f541da3b9620daf0805b4de3</citedby><cites>FETCH-LOGICAL-c380t-d176d6d24b90a877e1c12ebe156f48742d90033f4f541da3b9620daf0805b4de3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28426105$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pruneri, G.</creatorcontrib><creatorcontrib>Lazzeroni, M.</creatorcontrib><creatorcontrib>Bagnardi, V.</creatorcontrib><creatorcontrib>Tiburzio, G.B.</creatorcontrib><creatorcontrib>Rotmensz, N.</creatorcontrib><creatorcontrib>DeCensi, A.</creatorcontrib><creatorcontrib>Guerrieri-Gonzaga, A.</creatorcontrib><creatorcontrib>Vingiani, A.</creatorcontrib><creatorcontrib>Curigliano, G.</creatorcontrib><creatorcontrib>Zurrida, S.</creatorcontrib><creatorcontrib>Bassi, F.</creatorcontrib><creatorcontrib>Salgado, R.</creatorcontrib><creatorcontrib>Van den Eynden, G.</creatorcontrib><creatorcontrib>Loi, S.</creatorcontrib><creatorcontrib>Denkert, C.</creatorcontrib><creatorcontrib>Bonanni, B.</creatorcontrib><creatorcontrib>Viale, G.</creatorcontrib><title>The prevalence and clinical relevance of tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ of the breast</title><title>Annals of oncology</title><addtitle>Ann Oncol</addtitle><description>Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct in invasive breast cancer, but their clinical role in ductal carcinoma in situ (DCIS) has not been ascertained.
We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women with a median follow-up of 8.2years. Detailed criteria for TILs evaluation were pre-defined involving the International Immuno-Oncology Biomarker Working Group. TILs percentage was considered both as a continuous and categorical variable. Levels of TILs were examined for their associations with ipsilateral breast event (IBE), whether in situ or invasive.
Of the 1488 patients with DCIS under study, 35.1% had <1%, 58.3% 1–49% and 6.5% ≥50% peri-ductal stromal lymphocytes. The interobserver agreement in TILs evaluation, measured by the intraclass correlation coefficient (ICC) was 0.96 (95% CI 0.95–0.97). At univariable analysis, clinical factors significantly associated with TILs (P ≤0.001) were intrinsic subtype, grade, necrosis, type of surgery. Her-2 positive DCIS were more frequently associated with TILs (24% of patients with TILs ≥50%), followed by the triple negative (11%), Luminal B/Her-2 positive (9%) and Luminal A/B subtypes (1%) (P < 0.0001). We did not find any association between TILs as a continuous variable and the risk of IBEs. Likewise, when patients were stratified by TILs percentage (<1%, between 1% and 49.9%, and ≥50%), no statistically significant association was observed (10-year cumulative incidence of IBEs: 19%, 17.3%, and 18.7% respectively, P = 0.767).
TILs occur more frequently in the Her-2 positive DCIS. Although we did not find a significant association between TILs and the 10-year risk of IBE, our data suggest that immunotherapies might be considered in subsets of DCIS patients.</description><subject>Adult</subject><subject>Aged</subject><subject>Breast Neoplasms - epidemiology</subject><subject>Breast Neoplasms - immunology</subject><subject>Breast Neoplasms - pathology</subject><subject>Breast Neoplasms - therapy</subject><subject>Carcinoma, Intraductal, Noninfiltrating - epidemiology</subject><subject>Carcinoma, Intraductal, Noninfiltrating - immunology</subject><subject>Carcinoma, Intraductal, Noninfiltrating - pathology</subject><subject>Carcinoma, Intraductal, Noninfiltrating - therapy</subject><subject>ductal carcinoma in situ</subject><subject>Female</subject><subject>Humans</subject><subject>Lymphocytes, Tumor-Infiltrating - pathology</subject><subject>Middle Aged</subject><subject>Neoplasm Recurrence, Local - epidemiology</subject><subject>Neoplasm Recurrence, Local - immunology</subject><subject>Neoplasm Recurrence, Local - prevention & control</subject><subject>Prevalence</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>tumor infiltrating lymphocytes</subject><issn>0923-7534</issn><issn>1569-8041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kD1vFDEQhq0IRI5ASYtcJsUSf-2HSxQlIdJJNEdtee3ZxMhrH7Y35P49PvZIRzXSzDPvaB6EPlHyhRLJr3UIMZjr2f7uGD9DG9p2shmIoG_QhkjGm77l4hy9z_knIaSTTL5D52wQrKOk3aCX3RPgfYJn7SEYwDpYbLwLzmiPE_g6OLbjhMsyx9S4MDlfki4uPGJ_mPdP0RwKZHy5e9jmK-wCtospddnoZFyIsz72sivL35B6bUygc_mA3k7aZ_h4qhfox93t7uZbs_1-_3DzddsYPpDSWNp3trNMjJLooe-BGspghPrmJIZeMCsJ4XwSUyuo1XyUHSNWT2Qg7Sgs8At0uebuU_y1QC5qdtmA9zpAXLKig6weCW15RZsVNSnmnGBS--RmnQ6KEnWUrVbZapVd-c-n6GWcwb7S_-xWoF8BqA8-O0gqG3fUbF0CU5SN7j_RfwDfoJHD</recordid><startdate>201702</startdate><enddate>201702</enddate><creator>Pruneri, G.</creator><creator>Lazzeroni, M.</creator><creator>Bagnardi, V.</creator><creator>Tiburzio, G.B.</creator><creator>Rotmensz, N.</creator><creator>DeCensi, A.</creator><creator>Guerrieri-Gonzaga, A.</creator><creator>Vingiani, A.</creator><creator>Curigliano, G.</creator><creator>Zurrida, S.</creator><creator>Bassi, F.</creator><creator>Salgado, R.</creator><creator>Van den Eynden, G.</creator><creator>Loi, S.</creator><creator>Denkert, C.</creator><creator>Bonanni, B.</creator><creator>Viale, G.</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</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></search><sort><creationdate>201702</creationdate><title>The prevalence and clinical relevance of tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ of the breast</title><author>Pruneri, G. ; Lazzeroni, M. ; Bagnardi, V. ; Tiburzio, G.B. ; Rotmensz, N. ; DeCensi, A. ; Guerrieri-Gonzaga, A. ; Vingiani, A. ; Curigliano, G. ; Zurrida, S. ; Bassi, F. ; Salgado, R. ; Van den Eynden, G. ; Loi, S. ; Denkert, C. ; Bonanni, B. ; Viale, G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c380t-d176d6d24b90a877e1c12ebe156f48742d90033f4f541da3b9620daf0805b4de3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Breast Neoplasms - epidemiology</topic><topic>Breast Neoplasms - immunology</topic><topic>Breast Neoplasms - pathology</topic><topic>Breast Neoplasms - therapy</topic><topic>Carcinoma, Intraductal, Noninfiltrating - epidemiology</topic><topic>Carcinoma, Intraductal, Noninfiltrating - immunology</topic><topic>Carcinoma, Intraductal, Noninfiltrating - pathology</topic><topic>Carcinoma, Intraductal, Noninfiltrating - therapy</topic><topic>ductal carcinoma in situ</topic><topic>Female</topic><topic>Humans</topic><topic>Lymphocytes, Tumor-Infiltrating - pathology</topic><topic>Middle Aged</topic><topic>Neoplasm Recurrence, Local - epidemiology</topic><topic>Neoplasm Recurrence, Local - immunology</topic><topic>Neoplasm Recurrence, Local - prevention & control</topic><topic>Prevalence</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>tumor infiltrating lymphocytes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pruneri, G.</creatorcontrib><creatorcontrib>Lazzeroni, M.</creatorcontrib><creatorcontrib>Bagnardi, V.</creatorcontrib><creatorcontrib>Tiburzio, G.B.</creatorcontrib><creatorcontrib>Rotmensz, N.</creatorcontrib><creatorcontrib>DeCensi, A.</creatorcontrib><creatorcontrib>Guerrieri-Gonzaga, A.</creatorcontrib><creatorcontrib>Vingiani, A.</creatorcontrib><creatorcontrib>Curigliano, G.</creatorcontrib><creatorcontrib>Zurrida, S.</creatorcontrib><creatorcontrib>Bassi, F.</creatorcontrib><creatorcontrib>Salgado, R.</creatorcontrib><creatorcontrib>Van den Eynden, G.</creatorcontrib><creatorcontrib>Loi, S.</creatorcontrib><creatorcontrib>Denkert, C.</creatorcontrib><creatorcontrib>Bonanni, B.</creatorcontrib><creatorcontrib>Viale, G.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect: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>MEDLINE - Academic</collection><jtitle>Annals of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pruneri, G.</au><au>Lazzeroni, M.</au><au>Bagnardi, V.</au><au>Tiburzio, G.B.</au><au>Rotmensz, N.</au><au>DeCensi, A.</au><au>Guerrieri-Gonzaga, A.</au><au>Vingiani, A.</au><au>Curigliano, G.</au><au>Zurrida, S.</au><au>Bassi, F.</au><au>Salgado, R.</au><au>Van den Eynden, G.</au><au>Loi, S.</au><au>Denkert, C.</au><au>Bonanni, B.</au><au>Viale, G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The prevalence and clinical relevance of tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ of the breast</atitle><jtitle>Annals of oncology</jtitle><addtitle>Ann Oncol</addtitle><date>2017-02</date><risdate>2017</risdate><volume>28</volume><issue>2</issue><spage>321</spage><epage>328</epage><pages>321-328</pages><issn>0923-7534</issn><eissn>1569-8041</eissn><abstract>Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct in invasive breast cancer, but their clinical role in ductal carcinoma in situ (DCIS) has not been ascertained.
We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women with a median follow-up of 8.2years. Detailed criteria for TILs evaluation were pre-defined involving the International Immuno-Oncology Biomarker Working Group. TILs percentage was considered both as a continuous and categorical variable. Levels of TILs were examined for their associations with ipsilateral breast event (IBE), whether in situ or invasive.
Of the 1488 patients with DCIS under study, 35.1% had <1%, 58.3% 1–49% and 6.5% ≥50% peri-ductal stromal lymphocytes. The interobserver agreement in TILs evaluation, measured by the intraclass correlation coefficient (ICC) was 0.96 (95% CI 0.95–0.97). At univariable analysis, clinical factors significantly associated with TILs (P ≤0.001) were intrinsic subtype, grade, necrosis, type of surgery. Her-2 positive DCIS were more frequently associated with TILs (24% of patients with TILs ≥50%), followed by the triple negative (11%), Luminal B/Her-2 positive (9%) and Luminal A/B subtypes (1%) (P < 0.0001). We did not find any association between TILs as a continuous variable and the risk of IBEs. Likewise, when patients were stratified by TILs percentage (<1%, between 1% and 49.9%, and ≥50%), no statistically significant association was observed (10-year cumulative incidence of IBEs: 19%, 17.3%, and 18.7% respectively, P = 0.767).
TILs occur more frequently in the Her-2 positive DCIS. Although we did not find a significant association between TILs and the 10-year risk of IBE, our data suggest that immunotherapies might be considered in subsets of DCIS patients.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28426105</pmid><doi>10.1093/annonc/mdw623</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Breast Neoplasms - epidemiology Breast Neoplasms - immunology Breast Neoplasms - pathology Breast Neoplasms - therapy Carcinoma, Intraductal, Noninfiltrating - epidemiology Carcinoma, Intraductal, Noninfiltrating - immunology Carcinoma, Intraductal, Noninfiltrating - pathology Carcinoma, Intraductal, Noninfiltrating - therapy ductal carcinoma in situ Female Humans Lymphocytes, Tumor-Infiltrating - pathology Middle Aged Neoplasm Recurrence, Local - epidemiology Neoplasm Recurrence, Local - immunology Neoplasm Recurrence, Local - prevention & control Prevalence Prognosis Proportional Hazards Models tumor infiltrating lymphocytes |
| title | The prevalence and clinical relevance of tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ of the breast |
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