{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:18:28Z","timestamp":1790396308060,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2010,7,26]],"date-time":"2010-07-26T00:00:00Z","timestamp":1280102400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2010,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>Only a portion of breast cancer patients currently selected for trastuzumab therapy respond.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>Using a novel assay (HERmark) to quantify total human epidermal growth factor receptor 2 (HER2) expression, the authors examined outcomes in 102 trastuzumab\u2010treated metastatic breast cancer patients previously assessed as immunohistochemistry (IHC) 3+ by local but not central IHC, or fluorescence in situ hybridization (FISH) positive, and then retested by central FISH.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>Of 102 MBC patients previously scored as IHC 3+ or 2+\/FISH\u2010positive and treated with trastuzumab\u2010containing regimens, 98 had both central FISH and HER2 total expression values. Sixty\u2010six of 76 central FISH\u2010positive patients (87%) had high HER2 total expression levels (concordant positive), and 19 of 22 central FISH\u2010negative patients (86%) were HER2 total expression low (concordant negative). Fourteen percent (3 of 22) of central FISH\u2010negative patients were HER2 total expression high (discordant HER2 total expression high), and 13% (10 of 76) of central FISH\u2010positive patients were HER2 total expression low (discordant HER2 total expression low). The concordant positive group had a significantly longer time to progression (TTP, median = 11.3 months) compared with the concordant negative group (median TTP, 4.5 months; hazard ratio [HR] = 0.42, <jats:italic>P<\/jats:italic> &lt; .001), and also compared with the discordant HER2 total expression low group (median TTP, 3.7 months; HR = 0.43, <jats:italic>P<\/jats:italic> = .01). The discordant HER2 total expression low group behaved similarly compared with concordant negatives (HR = 1, <jats:italic>P<\/jats:italic> = .99). In analyses restricted to central FISH\u2010positive patients only (n = 77), Cox proportional hazards multivariate regression identified HER2 total expression as an independent predictor of TTP (HR = 0.29, <jats:italic>P<\/jats:italic> = .0015) and overall survival (HR = 0.19, <jats:italic>P<\/jats:italic> &lt; .001).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>A subset of patients with <jats:italic>HER2<\/jats:italic> gene amplification by FISH express low levels of HER2 protein and have reduced response to trastuzumab\u2010containing therapy, similar to FISH\u2010negative patients. This cohort represents a training dataset, and the observed relationships and derived cutoffs require validation in an independent cohort of trastuzumab\u2010treated metastatic breast cancer patients. Cancer 2010. \u00a9 2010 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.25430","type":"journal-article","created":{"date-parts":[[2010,7,26]],"date-time":"2010-07-26T12:13:28Z","timestamp":1280146408000},"page":"5168-5178","source":"Crossref","is-referenced-by-count":47,"title":["Quantitative HER2 protein levels predict outcome in fluorescence in situ hybridization\u2010positive patients with metastatic breast cancer treated with trastuzumab"],"prefix":"10.1002","volume":"116","author":[{"given":"Allan","family":"Lipton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang J.","family":"K\u00f6stler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Leitzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhail M.","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Sperinde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi","family":"Weidler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Paquet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Sherwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Trastuzumab Response Biomarker Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,11,3]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.9.2639"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052306"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052122"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200103153441101"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.20.3.719"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/35052073"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.3109\/07357909009017573"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3289120"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3798106"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2470152"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.11.012"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.21.3651"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.03.4744"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-0636"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.09.094"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.2775"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0801440"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djm075"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2008.02.003"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-0385-3"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji237"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/PDM.0b013e31818cbdb2"},{"key":"e_1_2_7_24_2","article-title":"Analytical validation of a highly quantitative, sensitive, accurate, and reproducible assay (HERmark\u2122) for the measurement of HER2 total protein and HER2 homodimers in FFPE breast cancer tumor specimens","author":"Larson J","journal-title":"Pathol Res Int."},{"key":"e_1_2_7_25_2","article-title":"Quantitation of p95HER2 in paraffin sections using a p95\u2010specific antibody and correlation with outcome in a cohort of trastuzumab\u2010treated breast cancer patients","author":"Sperinde J","journal-title":"Clin Cancer Res."}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.25430","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.25430","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T14:59:23Z","timestamp":1760281163000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.25430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11,3]]},"references-count":24,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2010,11,15]]}},"alternative-id":["10.1002\/cncr.25430"],"URL":"https:\/\/doi.org\/10.1002\/cncr.25430","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,11,3]]}}}