{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:07:23Z","timestamp":1784646443916,"version":"3.55.0"},"reference-count":37,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n \n ERBB2<\/jats:italic>\n (formerly termed\n HER2<\/jats:italic>\n )-low gastric cancer (GC) has recently gained attention with the development of novel\n ERBB2<\/jats:italic>\n -targeted therapies; however, its clinicopathologic features and prognostic significance compared with\n ERBB2<\/jats:italic>\n -null disease remain unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To compare clinicopathologic characteristics of\n ERBB2<\/jats:italic>\n -low and\n ERBB2<\/jats:italic>\n -null advanced GC and assess whether\n ERBB2<\/jats:italic>\n status is independently associated with survival outcomes.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This international, multicenter retrospective cohort study included patients aged 18 years or older diagnosed with advanced metastatic GC between January 2018 and June 2025 at 6 oncology centers across Turkey and Spain. Eligible patients were those with\n ERBB2<\/jats:italic>\n -negative disease (\n ERBB2<\/jats:italic>\n -low [immunohistochemistry (IHC) score of 1+ or IHC score of 2+ with negative in situ hybridization] or\n ERBB2<\/jats:italic>\n -null [IHC score of 0]), consecutively identified from institutional databases. All eligible patients during the study period were included.\n <\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n \n ERBB2<\/jats:italic>\n expression status, categorized as\n ERBB2<\/jats:italic>\n -low or\n ERBB2<\/jats:italic>\n -null.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcomes were progression-free survival (PFS) and overall survival (OS). Factors associated with PFS or OS were evaluated using univariate and multivariable Cox proportional hazards regression models.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 522 patients with GC (median [IQR] age, 60 [51-69] years; 345 [66.1%] male), 222 (42.5%) had\n ERBB2<\/jats:italic>\n -low tumors and 300 (57.5%) had\n ERBB2<\/jats:italic>\n -null tumors. Patients with\n ERBB2<\/jats:italic>\n -low GC were older (median [IQR], 62 [53-70] years vs 59 [50-67] years;\n P<\/jats:italic>\n \u2009=\u2009.03) and more often male (159 [71.6%] vs 186 [62.0%];\n P<\/jats:italic>\n \u2009=\u2009.03) and had worse Eastern Cooperative Oncology Group (ECOG) performance status (39 [17.6%] vs 33 [11.0%] had ECOG score \u22652;\n P<\/jats:italic>\n \u2009=\u2009.04). Liver metastases were more common in the\n ERBB2<\/jats:italic>\n -low group (107 patients [48.2%] vs 98 [32.7%];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), as were elevated carcinoembryonic antigen levels (104 of 189 patients [55.0%] vs 89 of 234 [38.0%];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). Among patients receiving first-line therapy (488 [93.5%]), median PFS was shorter in the\n ERBB2<\/jats:italic>\n -low than in the\n ERBB2<\/jats:italic>\n -null group (7.2 months [95% CI, 6.2-8.3 months] vs 8.7 months [95% CI, 7.9-9.6 months]; HR, 1.36 [95% CI, 1.11-1.66];\n P<\/jats:italic>\n \u2009=\u2009.003), as was median OS (15.8 months [95% CI, 14.1-17.5 months] vs 23.1 months [95% CI, 19.4-26.8 months]; HR, 1.34 [95% CI, 1.09-1.64];\n P<\/jats:italic>\n \u2009=\u2009.006). However,\n ERBB2<\/jats:italic>\n status was not an independent factor associated with survival (PFS: HR, 1.16 [95% CI, 0.93-1.46];\n P<\/jats:italic>\n \u2009=\u2009.20; OS: HR, 1.13 [95% CI, 0.89-1.44];\n P<\/jats:italic>\n \u2009=\u2009.31).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n In this cohort study of patients with advanced GC,\n ERBB2<\/jats:italic>\n -low compared with\n ERBB2<\/jats:italic>\n -null tumors were associated with inferior survival; however,\n ERBB2<\/jats:italic>\n status was not an independent factor associated with survival, indicating that survival differences may have been largely attributable to unfavorable baseline clinical characteristics rather than\n ERBB2<\/jats:italic>\n expression itself. These findings suggest that\n ERBB2<\/jats:italic>\n -low status alone may be insufficient for prognostic stratification.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.24180","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:00:26Z","timestamp":1784646026000},"page":"e2624180","source":"Crossref","is-referenced-by-count":0,"title":["Survival Outcomes in\n ERBB2-<\/i>\n Low vs\n ERBB2-<\/i>\n Null Advanced Gastric Cancer"],"prefix":"10.1001","volume":"9","author":[{"given":"Beliz Bahar","family":"Karao\u011flan","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Ankara University Faculty of Medicine, Ankara, Turkey"},{"name":"Ankara University Cancer Research Institute, Ankara, Turkey"},{"name":"Eskisehir City Hospital, Eskisehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Ter\u00e1n","sequence":"additional","affiliation":[{"name":"Gastrointestinal Cancer Unit, Vall d\u2019Hebron Institute of Oncology (VHIO), Vall d\u2019Hebron University Hospital, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pau","family":"Mascar\u00f3 Baselga","sequence":"additional","affiliation":[{"name":"Gastrointestinal Cancer Unit, Vall d\u2019Hebron Institute of Oncology (VHIO), Vall d\u2019Hebron University Hospital, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Zuchiatti","sequence":"additional","affiliation":[{"name":"Pathology Department, Vall d\u2019Hebron University Hospital, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirmehdi","family":"Mehdiyev","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ankara Bilkent City Hospital, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seher","family":"Kaya","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ankara Etlik City Hospital, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cevat \u0130lteri\u015f","family":"K\u0131k\u0131l\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ko\u00e7 University Faculty of Medicine, \u0130stanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmut","family":"Kara","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Van Y\u00fcz\u00fcnc\u00fc Y\u0131l University, Van, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahriye Tu\u011fba","family":"K\u00f6\u015f","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ankara Bilkent City Hospital, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u0131l\u015fa M\u0131zrak","family":"Kaya","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ankara Etlik City Hospital, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Sel\u00e7ukbiricik","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ko\u00e7 University Faculty of Medicine, \u0130stanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muslih","family":"\u00dcr\u00fcn","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Van Y\u00fcz\u00fcnc\u00fc Y\u0131l University, Van, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u0131nar Kubilay","family":"Tolunay","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ankara University Faculty of Medicine, Ankara, Turkey"},{"name":"Ankara University Cancer Research Institute, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"issue":"3","key":"zoi260682r1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"issue":"10","key":"zoi260682r2","doi-asserted-by":"publisher","first-page":"2656","DOI":"10.1093\/annonc\/mds104","article-title":"Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis.","volume":"23","author":"Janjigian","year":"2012","journal-title":"Ann Oncol"},{"key":"zoi260682r3","doi-asserted-by":"crossref","DOI":"10.1093\/annonc\/mdy269.101","article-title":"103P-prevalence of CLDN18.2, HER2 and PD-L1 in gastric cancer samples","volume":"29","author":"Moran","year":"2018","journal-title":". 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