Evaluation of the Predictive Role of Tumor Immune Infiltrate in Patients with HER2-Positive Breast Cancer Treated with Neoadjuvant Anti-HER2 Therapy without Chemotherapy
Tumor-infiltrating lymphocytes (TIL) are associated with benefit to trastuzumab and chemotherapy in patients with early-stage HER2 breast cancer. The predictive value of TILs, TIL subsets, and other immune cells in patients receiving chemotherapy-sparing lapatinib plus trastuzumab treatment is uncle...
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| Veröffentlicht in: | Clinical cancer research 2020-02, Vol.26 (3), p.738-745 |
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| creator | De Angelis, Carmine Nagi, Chandandeep Hoyt, Cliff C Liu, Linying Roman, Kristin Wang, Chichung Zheng, Yi Veeraraghavan, Jamunarani Sethunath, Vidyalakshmi Nuciforo, Paolo Wang, Tao Tsimelzon, Anna Mao, Sufeng Hilsenbeck, Susan G Trivedi, Meghana V Cataldo, Maria Letizia Pavlick, Anne Wolff, Antonio C Weigelt, Britta Reis-Filho, Jorge S Prat, Aleix Gutierrez, Carolina Osborne, Charles Kent Rimawi, Mothaffar F Schiff, Rachel |
| description | Tumor-infiltrating lymphocytes (TIL) are associated with benefit to trastuzumab and chemotherapy in patients with early-stage HER2
breast cancer. The predictive value of TILs, TIL subsets, and other immune cells in patients receiving chemotherapy-sparing lapatinib plus trastuzumab treatment is unclear.
Hematoxylin and eosin-stained slides (
= 59) were used to score stromal (s-)TILs from pretreatment biopsies of patients enrolled in the neoadjuvant TBCRC006 trial of 12-week lapatinib plus trastuzumab therapy (plus endocrine therapy for ER
tumors). A 60% threshold was used to define lymphocyte-predominant breast cancer (LPBC). Multiplexed immunofluorescence (m-IF) staining (CD4, CD8, CD20, CD68, and FoxP3) and multispectral imaging were performed to characterize immune infiltrates in single formalin-fixed paraffin-embedded slides (
= 33).
The pathologic complete response (pCR) rate was numerically higher in patients with LPBC compared with patients with non-LPBC (50% vs. 19%,
= 0.057). Unsupervised hierarchical clustering of the five immune markers identified two patient clusters with different responses to lapatinib plus trastuzumab treatment (pCR = 7% vs. 50%, for cluster 1 vs. 2 respectively;
= 0.01). In multivariable analysis, cluster 2, characterized by high CD4
, CD8
, CD20
s-TILs, and high CD20
intratumoral TILs, was independently associated with a higher pCR rate (
= 0.03). Analysis of single immune subpopulations revealed a significant association of pCR with higher baseline infiltration by s-CD4, intratumoral (i-) CD4, and i-CD20
TILs.
LPBC was marginally associated with higher pCR rate than non-LPBC in patients with lapatinib plus trastuzumab treated HER2
breast cancer. Quantitative assessment of the immune infiltrate by m-IF is feasible and may help correlate individual immune cell subpopulations and immune cell profiles with treatment response. |
| doi_str_mv | 10.1158/1078-0432.CCR-19-1402 |
| format | Article |
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breast cancer. The predictive value of TILs, TIL subsets, and other immune cells in patients receiving chemotherapy-sparing lapatinib plus trastuzumab treatment is unclear.
Hematoxylin and eosin-stained slides (
= 59) were used to score stromal (s-)TILs from pretreatment biopsies of patients enrolled in the neoadjuvant TBCRC006 trial of 12-week lapatinib plus trastuzumab therapy (plus endocrine therapy for ER
tumors). A 60% threshold was used to define lymphocyte-predominant breast cancer (LPBC). Multiplexed immunofluorescence (m-IF) staining (CD4, CD8, CD20, CD68, and FoxP3) and multispectral imaging were performed to characterize immune infiltrates in single formalin-fixed paraffin-embedded slides (
= 33).
The pathologic complete response (pCR) rate was numerically higher in patients with LPBC compared with patients with non-LPBC (50% vs. 19%,
= 0.057). Unsupervised hierarchical clustering of the five immune markers identified two patient clusters with different responses to lapatinib plus trastuzumab treatment (pCR = 7% vs. 50%, for cluster 1 vs. 2 respectively;
= 0.01). In multivariable analysis, cluster 2, characterized by high CD4
, CD8
, CD20
s-TILs, and high CD20
intratumoral TILs, was independently associated with a higher pCR rate (
= 0.03). Analysis of single immune subpopulations revealed a significant association of pCR with higher baseline infiltration by s-CD4, intratumoral (i-) CD4, and i-CD20
TILs.
LPBC was marginally associated with higher pCR rate than non-LPBC in patients with lapatinib plus trastuzumab treated HER2
breast cancer. Quantitative assessment of the immune infiltrate by m-IF is feasible and may help correlate individual immune cell subpopulations and immune cell profiles with treatment response.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-19-1402</identifier><identifier>PMID: 31653641</identifier><language>eng</language><publisher>United States</publisher><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Breast Neoplasms - drug therapy ; Breast Neoplasms - immunology ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Female ; Follow-Up Studies ; Humans ; Lapatinib - administration & dosage ; Lymphocytes - drug effects ; Lymphocytes - immunology ; Lymphocytes, Tumor-Infiltrating - drug effects ; Lymphocytes, Tumor-Infiltrating - immunology ; Middle Aged ; Neoadjuvant Therapy - methods ; Prognosis ; Receptor, ErbB-2 - immunology ; Receptor, ErbB-2 - metabolism ; Trastuzumab - administration & dosage</subject><ispartof>Clinical cancer research, 2020-02, Vol.26 (3), p.738-745</ispartof><rights>2019 American Association for Cancer Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-d77464b2bd395d39f814392901b872369d324bd1a1015144a152f8b9fd94bdcb3</citedby><cites>FETCH-LOGICAL-c408t-d77464b2bd395d39f814392901b872369d324bd1a1015144a152f8b9fd94bdcb3</cites><orcidid>0000-0002-7962-673X ; 0000-0003-1957-7160 ; 0000-0003-1696-5213 ; 0000-0003-1380-0990 ; 0000-0003-3734-1063 ; 0000-0002-0585-5580</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3343,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31653641$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>De Angelis, Carmine</creatorcontrib><creatorcontrib>Nagi, Chandandeep</creatorcontrib><creatorcontrib>Hoyt, Cliff C</creatorcontrib><creatorcontrib>Liu, Linying</creatorcontrib><creatorcontrib>Roman, Kristin</creatorcontrib><creatorcontrib>Wang, Chichung</creatorcontrib><creatorcontrib>Zheng, Yi</creatorcontrib><creatorcontrib>Veeraraghavan, Jamunarani</creatorcontrib><creatorcontrib>Sethunath, Vidyalakshmi</creatorcontrib><creatorcontrib>Nuciforo, Paolo</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Tsimelzon, Anna</creatorcontrib><creatorcontrib>Mao, Sufeng</creatorcontrib><creatorcontrib>Hilsenbeck, Susan G</creatorcontrib><creatorcontrib>Trivedi, Meghana V</creatorcontrib><creatorcontrib>Cataldo, Maria Letizia</creatorcontrib><creatorcontrib>Pavlick, Anne</creatorcontrib><creatorcontrib>Wolff, Antonio C</creatorcontrib><creatorcontrib>Weigelt, Britta</creatorcontrib><creatorcontrib>Reis-Filho, Jorge S</creatorcontrib><creatorcontrib>Prat, Aleix</creatorcontrib><creatorcontrib>Gutierrez, Carolina</creatorcontrib><creatorcontrib>Osborne, Charles Kent</creatorcontrib><creatorcontrib>Rimawi, Mothaffar F</creatorcontrib><creatorcontrib>Schiff, Rachel</creatorcontrib><title>Evaluation of the Predictive Role of Tumor Immune Infiltrate in Patients with HER2-Positive Breast Cancer Treated with Neoadjuvant Anti-HER2 Therapy without Chemotherapy</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Tumor-infiltrating lymphocytes (TIL) are associated with benefit to trastuzumab and chemotherapy in patients with early-stage HER2
breast cancer. The predictive value of TILs, TIL subsets, and other immune cells in patients receiving chemotherapy-sparing lapatinib plus trastuzumab treatment is unclear.
Hematoxylin and eosin-stained slides (
= 59) were used to score stromal (s-)TILs from pretreatment biopsies of patients enrolled in the neoadjuvant TBCRC006 trial of 12-week lapatinib plus trastuzumab therapy (plus endocrine therapy for ER
tumors). A 60% threshold was used to define lymphocyte-predominant breast cancer (LPBC). Multiplexed immunofluorescence (m-IF) staining (CD4, CD8, CD20, CD68, and FoxP3) and multispectral imaging were performed to characterize immune infiltrates in single formalin-fixed paraffin-embedded slides (
= 33).
The pathologic complete response (pCR) rate was numerically higher in patients with LPBC compared with patients with non-LPBC (50% vs. 19%,
= 0.057). Unsupervised hierarchical clustering of the five immune markers identified two patient clusters with different responses to lapatinib plus trastuzumab treatment (pCR = 7% vs. 50%, for cluster 1 vs. 2 respectively;
= 0.01). In multivariable analysis, cluster 2, characterized by high CD4
, CD8
, CD20
s-TILs, and high CD20
intratumoral TILs, was independently associated with a higher pCR rate (
= 0.03). Analysis of single immune subpopulations revealed a significant association of pCR with higher baseline infiltration by s-CD4, intratumoral (i-) CD4, and i-CD20
TILs.
LPBC was marginally associated with higher pCR rate than non-LPBC in patients with lapatinib plus trastuzumab treated HER2
breast cancer. Quantitative assessment of the immune infiltrate by m-IF is feasible and may help correlate individual immune cell subpopulations and immune cell profiles with treatment response.</description><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - immunology</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Lapatinib - administration & dosage</subject><subject>Lymphocytes - drug effects</subject><subject>Lymphocytes - immunology</subject><subject>Lymphocytes, Tumor-Infiltrating - drug effects</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Middle Aged</subject><subject>Neoadjuvant Therapy - methods</subject><subject>Prognosis</subject><subject>Receptor, ErbB-2 - immunology</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Trastuzumab - administration & dosage</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kctu2zAQRYWiQfNoP6EFl90o5fAhictUcBIDQWsYzpqgpBHMQBJdknKRT-pfhoqTLojhXNxDLk6WfQV6DSCrH0DLKqeCs-u63uagchCUfcguQMoy56yQH9P9vXOeXYbwRCkIoOJTds6hkLwQcJH9Wx3NMJto3URcT-IeycZjZ9toj0i2bsAl3s2j82Q9jvOEZD31dojeRCR2IpvE4hQD-WvjntyvtizfuGBf8Z8eTYikNlOLnuzSFrE7FX-hM93TfDRTJDdTtPlCkt0evTk8v1bcnMg9ji6ews_ZWW-GgF_e5lX2eLva1ff5w--7dX3zkLeCVjHvylIUomFNx5VMp69AcMUUhaYqGS9Ux5loOjBAQYIQBiTrq0b1nUpx2_Cr7Pvp3YN3f2YMUY82tDgMZkI3B804VZLyElSqylO19S4Ej70-eDsa_6yB6sWSXgzoxYBOljQovVhK3Le3L-ZmxO4_9a6FvwDUoI8Y</recordid><startdate>20200201</startdate><enddate>20200201</enddate><creator>De Angelis, Carmine</creator><creator>Nagi, Chandandeep</creator><creator>Hoyt, Cliff C</creator><creator>Liu, Linying</creator><creator>Roman, Kristin</creator><creator>Wang, Chichung</creator><creator>Zheng, Yi</creator><creator>Veeraraghavan, Jamunarani</creator><creator>Sethunath, Vidyalakshmi</creator><creator>Nuciforo, Paolo</creator><creator>Wang, Tao</creator><creator>Tsimelzon, Anna</creator><creator>Mao, Sufeng</creator><creator>Hilsenbeck, Susan G</creator><creator>Trivedi, Meghana V</creator><creator>Cataldo, Maria Letizia</creator><creator>Pavlick, Anne</creator><creator>Wolff, Antonio C</creator><creator>Weigelt, Britta</creator><creator>Reis-Filho, Jorge S</creator><creator>Prat, Aleix</creator><creator>Gutierrez, Carolina</creator><creator>Osborne, Charles Kent</creator><creator>Rimawi, Mothaffar F</creator><creator>Schiff, Rachel</creator><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><orcidid>https://orcid.org/0000-0002-7962-673X</orcidid><orcidid>https://orcid.org/0000-0003-1957-7160</orcidid><orcidid>https://orcid.org/0000-0003-1696-5213</orcidid><orcidid>https://orcid.org/0000-0003-1380-0990</orcidid><orcidid>https://orcid.org/0000-0003-3734-1063</orcidid><orcidid>https://orcid.org/0000-0002-0585-5580</orcidid></search><sort><creationdate>20200201</creationdate><title>Evaluation of the Predictive Role of Tumor Immune Infiltrate in Patients with HER2-Positive Breast Cancer Treated with Neoadjuvant Anti-HER2 Therapy without Chemotherapy</title><author>De Angelis, Carmine ; Nagi, Chandandeep ; Hoyt, Cliff C ; Liu, Linying ; Roman, Kristin ; Wang, Chichung ; Zheng, Yi ; Veeraraghavan, Jamunarani ; Sethunath, Vidyalakshmi ; Nuciforo, Paolo ; Wang, Tao ; Tsimelzon, Anna ; Mao, Sufeng ; Hilsenbeck, Susan G ; Trivedi, Meghana V ; Cataldo, Maria Letizia ; Pavlick, Anne ; Wolff, Antonio C ; Weigelt, Britta ; Reis-Filho, Jorge S ; Prat, Aleix ; Gutierrez, Carolina ; Osborne, Charles Kent ; Rimawi, Mothaffar F ; Schiff, Rachel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-d77464b2bd395d39f814392901b872369d324bd1a1015144a152f8b9fd94bdcb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - immunology</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Lapatinib - administration & dosage</topic><topic>Lymphocytes - drug effects</topic><topic>Lymphocytes - immunology</topic><topic>Lymphocytes, Tumor-Infiltrating - drug effects</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Middle Aged</topic><topic>Neoadjuvant Therapy - methods</topic><topic>Prognosis</topic><topic>Receptor, ErbB-2 - immunology</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>Trastuzumab - administration & dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>De Angelis, Carmine</creatorcontrib><creatorcontrib>Nagi, Chandandeep</creatorcontrib><creatorcontrib>Hoyt, Cliff C</creatorcontrib><creatorcontrib>Liu, Linying</creatorcontrib><creatorcontrib>Roman, Kristin</creatorcontrib><creatorcontrib>Wang, Chichung</creatorcontrib><creatorcontrib>Zheng, Yi</creatorcontrib><creatorcontrib>Veeraraghavan, Jamunarani</creatorcontrib><creatorcontrib>Sethunath, Vidyalakshmi</creatorcontrib><creatorcontrib>Nuciforo, Paolo</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Tsimelzon, Anna</creatorcontrib><creatorcontrib>Mao, Sufeng</creatorcontrib><creatorcontrib>Hilsenbeck, Susan G</creatorcontrib><creatorcontrib>Trivedi, Meghana V</creatorcontrib><creatorcontrib>Cataldo, Maria Letizia</creatorcontrib><creatorcontrib>Pavlick, Anne</creatorcontrib><creatorcontrib>Wolff, Antonio C</creatorcontrib><creatorcontrib>Weigelt, Britta</creatorcontrib><creatorcontrib>Reis-Filho, Jorge S</creatorcontrib><creatorcontrib>Prat, Aleix</creatorcontrib><creatorcontrib>Gutierrez, Carolina</creatorcontrib><creatorcontrib>Osborne, Charles Kent</creatorcontrib><creatorcontrib>Rimawi, Mothaffar F</creatorcontrib><creatorcontrib>Schiff, Rachel</creatorcontrib><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>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>De Angelis, Carmine</au><au>Nagi, Chandandeep</au><au>Hoyt, Cliff C</au><au>Liu, Linying</au><au>Roman, Kristin</au><au>Wang, Chichung</au><au>Zheng, Yi</au><au>Veeraraghavan, Jamunarani</au><au>Sethunath, Vidyalakshmi</au><au>Nuciforo, Paolo</au><au>Wang, Tao</au><au>Tsimelzon, Anna</au><au>Mao, Sufeng</au><au>Hilsenbeck, Susan G</au><au>Trivedi, Meghana V</au><au>Cataldo, Maria Letizia</au><au>Pavlick, Anne</au><au>Wolff, Antonio C</au><au>Weigelt, Britta</au><au>Reis-Filho, Jorge S</au><au>Prat, Aleix</au><au>Gutierrez, Carolina</au><au>Osborne, Charles Kent</au><au>Rimawi, Mothaffar F</au><au>Schiff, Rachel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of the Predictive Role of Tumor Immune Infiltrate in Patients with HER2-Positive Breast Cancer Treated with Neoadjuvant Anti-HER2 Therapy without Chemotherapy</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2020-02-01</date><risdate>2020</risdate><volume>26</volume><issue>3</issue><spage>738</spage><epage>745</epage><pages>738-745</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Tumor-infiltrating lymphocytes (TIL) are associated with benefit to trastuzumab and chemotherapy in patients with early-stage HER2
breast cancer. The predictive value of TILs, TIL subsets, and other immune cells in patients receiving chemotherapy-sparing lapatinib plus trastuzumab treatment is unclear.
Hematoxylin and eosin-stained slides (
= 59) were used to score stromal (s-)TILs from pretreatment biopsies of patients enrolled in the neoadjuvant TBCRC006 trial of 12-week lapatinib plus trastuzumab therapy (plus endocrine therapy for ER
tumors). A 60% threshold was used to define lymphocyte-predominant breast cancer (LPBC). Multiplexed immunofluorescence (m-IF) staining (CD4, CD8, CD20, CD68, and FoxP3) and multispectral imaging were performed to characterize immune infiltrates in single formalin-fixed paraffin-embedded slides (
= 33).
The pathologic complete response (pCR) rate was numerically higher in patients with LPBC compared with patients with non-LPBC (50% vs. 19%,
= 0.057). Unsupervised hierarchical clustering of the five immune markers identified two patient clusters with different responses to lapatinib plus trastuzumab treatment (pCR = 7% vs. 50%, for cluster 1 vs. 2 respectively;
= 0.01). In multivariable analysis, cluster 2, characterized by high CD4
, CD8
, CD20
s-TILs, and high CD20
intratumoral TILs, was independently associated with a higher pCR rate (
= 0.03). Analysis of single immune subpopulations revealed a significant association of pCR with higher baseline infiltration by s-CD4, intratumoral (i-) CD4, and i-CD20
TILs.
LPBC was marginally associated with higher pCR rate than non-LPBC in patients with lapatinib plus trastuzumab treated HER2
breast cancer. Quantitative assessment of the immune infiltrate by m-IF is feasible and may help correlate individual immune cell subpopulations and immune cell profiles with treatment response.</abstract><cop>United States</cop><pmid>31653641</pmid><doi>10.1158/1078-0432.CCR-19-1402</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-7962-673X</orcidid><orcidid>https://orcid.org/0000-0003-1957-7160</orcidid><orcidid>https://orcid.org/0000-0003-1696-5213</orcidid><orcidid>https://orcid.org/0000-0003-1380-0990</orcidid><orcidid>https://orcid.org/0000-0003-3734-1063</orcidid><orcidid>https://orcid.org/0000-0002-0585-5580</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 2020-02, Vol.26 (3), p.738-745 |
| issn | 1078-0432 1557-3265 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2309503719 |
| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Antineoplastic Combined Chemotherapy Protocols - therapeutic use Breast Neoplasms - drug therapy Breast Neoplasms - immunology Breast Neoplasms - metabolism Breast Neoplasms - pathology Female Follow-Up Studies Humans Lapatinib - administration & dosage Lymphocytes - drug effects Lymphocytes - immunology Lymphocytes, Tumor-Infiltrating - drug effects Lymphocytes, Tumor-Infiltrating - immunology Middle Aged Neoadjuvant Therapy - methods Prognosis Receptor, ErbB-2 - immunology Receptor, ErbB-2 - metabolism Trastuzumab - administration & dosage |
| title | Evaluation of the Predictive Role of Tumor Immune Infiltrate in Patients with HER2-Positive Breast Cancer Treated with Neoadjuvant Anti-HER2 Therapy without Chemotherapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-16T04%3A00%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Evaluation%20of%20the%20Predictive%20Role%20of%20Tumor%20Immune%20Infiltrate%20in%20Patients%20with%20HER2-Positive%20Breast%20Cancer%20Treated%20with%20Neoadjuvant%20Anti-HER2%20Therapy%20without%20Chemotherapy&rft.jtitle=Clinical%20cancer%20research&rft.au=De%20Angelis,%20Carmine&rft.date=2020-02-01&rft.volume=26&rft.issue=3&rft.spage=738&rft.epage=745&rft.pages=738-745&rft.issn=1078-0432&rft.eissn=1557-3265&rft_id=info:doi/10.1158/1078-0432.CCR-19-1402&rft_dat=%3Cproquest_cross%3E2309503719%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2309503719&rft_id=info:pmid/31653641&rfr_iscdi=true |