Association between HER2 heterogeneity and clinical outcomes of HER2-positive gastric cancer patients treated with trastuzumab
Background The GASTHER1 study showed that re-evaluation of HER2 status rescued 8% of HER2-positive gastric cancer (GC) patients with initially HER2-negative GC. Since rescued HER2 positivity represents HER2 heterogeneity, we aimed to investigate this in a larger cohort with longer follow-up duration...
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| Veröffentlicht in: | Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2022-07, Vol.25 (4), p.794-803 |
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| container_title | Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association |
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| creator | Bang, Kyunghye Cheon, Jaekyung Park, Young Soo Kim, Hyung-Don Ryu, Min-Hee Park, Yangsoon Moon, Meesun Lee, Hyungeun Kang, Yoon-Koo |
| description | Background
The GASTHER1 study showed that re-evaluation of HER2 status rescued 8% of HER2-positive gastric cancer (GC) patients with initially HER2-negative GC. Since rescued HER2 positivity represents HER2 heterogeneity, we aimed to investigate this in a larger cohort with longer follow-up duration.
Methods
Data of 153 HER2-positive advanced GC patients who received first-line trastuzumab-based chemotherapy were analyzed. Repeat endoscopic biopsy was performed in patients with initially HER2-negative GC. Survival outcomes were analyzed according to the immunohistochemistry (IHC) score (IHC 2+ /in situ hybridization [ISH] + vs IHC 3+), HER2 status (initially vs rescued HER2 positive), and H-score.
Results
IHC 2+ /ISH + patients showed worse progression-free survival (PFS) and overall survival (OS) than those with IHC 3+ (
p
|
| doi_str_mv | 10.1007/s10120-022-01298-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2661083440</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2680276740</sourcerecordid><originalsourceid>FETCH-LOGICAL-c443t-cdfcfde48fd3a501ea537f5f45513cff367bdcb346205042fd23bbf26f6885a73</originalsourceid><addsrcrecordid>eNp9kctLHTEUh0NR6qP9B7ooATfdTM175i5FfBSEgug6ZDIn18hMcptkKrrwb2-8jxa6cJUTznd-58CH0BdKvlNC2tNMCWWkIYw1tVh0jfqADqngquGcyL1dzRb0AB3l_EgIlQuqPqIDLiUTXccP0etZztF6U3wMuIfyBBDw9cUtww9QIMUlBPDlGZswYDv64K0ZcZyLjRNkHN2abVYx--J_A16aXJK32JpgIeFVzYVQMi4JTIEBP_nyUD-Vml_myfSf0L4zY4bP2_cY3V9e3J1fNzc_r36cn900VgheGjs46wYQnRu4kYSCkbx10gkpKbfOcdX2g-25UIxIIpgbGO97x5RTXSdNy4_Rt03uKsVfM-SiJ58tjKMJEOesmVKUdFwIUtGT_9DHOKdQr6tUR1ir2jXFNpRNMecETq-Sn0x61pToNzt6Y0dXO3ptR6s69HUbPfcTDH9HdjoqwDdArq2whPRv9zuxfwBMxpw4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2680276740</pqid></control><display><type>article</type><title>Association between HER2 heterogeneity and clinical outcomes of HER2-positive gastric cancer patients treated with trastuzumab</title><source>SpringerLink Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Bang, Kyunghye ; Cheon, Jaekyung ; Park, Young Soo ; Kim, Hyung-Don ; Ryu, Min-Hee ; Park, Yangsoon ; Moon, Meesun ; Lee, Hyungeun ; Kang, Yoon-Koo</creator><creatorcontrib>Bang, Kyunghye ; Cheon, Jaekyung ; Park, Young Soo ; Kim, Hyung-Don ; Ryu, Min-Hee ; Park, Yangsoon ; Moon, Meesun ; Lee, Hyungeun ; Kang, Yoon-Koo</creatorcontrib><description>Background
The GASTHER1 study showed that re-evaluation of HER2 status rescued 8% of HER2-positive gastric cancer (GC) patients with initially HER2-negative GC. Since rescued HER2 positivity represents HER2 heterogeneity, we aimed to investigate this in a larger cohort with longer follow-up duration.
Methods
Data of 153 HER2-positive advanced GC patients who received first-line trastuzumab-based chemotherapy were analyzed. Repeat endoscopic biopsy was performed in patients with initially HER2-negative GC. Survival outcomes were analyzed according to the immunohistochemistry (IHC) score (IHC 2+ /in situ hybridization [ISH] + vs IHC 3+), HER2 status (initially vs rescued HER2 positive), and H-score.
Results
IHC 2+ /ISH + patients showed worse progression-free survival (PFS) and overall survival (OS) than those with IHC 3+ (
p
< 0.05). Rescued HER2-positive patients showed worse PFS and OS than initially HER2-positive patients (
p
< 0.05). Although survival outcomes were comparable according to HER2 status in IHC 2+ /ISH + patients, initially HER2-positive patients showed more favorable PFS and OS than rescued HER2-positive patients (
p
< 0.05) among those with IHC 3+ . Among the subgroups determined by HER2 status and IHC score, the initially IHC 3+ subgroup had the highest H-score. The low H-score group (H-score ≤ 210) had significantly worse survival outcomes than the high H-score group (H-score > 210) (
p
< 0.05). An H-score of ≤ 210 was independently associated with shorter OS (HR = 1.54, 95% CI 1.02–2.31,
p
= 0.04).
Conclusions
Rescued HER2-positive patients showed worse clinical outcomes than initially HER2-positive patients, especially those with IHC 3+ . This finding highlights the impact of HER2 heterogeneity, which can be quantified indirectly as an H-score.</description><identifier>ISSN: 1436-3291</identifier><identifier>EISSN: 1436-3305</identifier><identifier>DOI: 10.1007/s10120-022-01298-6</identifier><identifier>PMID: 35524883</identifier><language>eng</language><publisher>Singapore: Springer Nature Singapore</publisher><subject>Abdominal Surgery ; Biopsy ; Cancer Research ; Chemotherapy ; Clinical outcomes ; ErbB-2 protein ; Gastric cancer ; Gastroenterology ; Hybridization ; Immunohistochemistry ; Medicine ; Medicine & Public Health ; Monoclonal antibodies ; Oncology ; Original Article ; Patients ; Surgical Oncology ; Survival ; Targeted cancer therapy ; Trastuzumab</subject><ispartof>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2022-07, Vol.25 (4), p.794-803</ispartof><rights>The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2022</rights><rights>2022. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.</rights><rights>The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2022.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-cdfcfde48fd3a501ea537f5f45513cff367bdcb346205042fd23bbf26f6885a73</citedby><cites>FETCH-LOGICAL-c443t-cdfcfde48fd3a501ea537f5f45513cff367bdcb346205042fd23bbf26f6885a73</cites><orcidid>0000-0003-0783-6583</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10120-022-01298-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10120-022-01298-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35524883$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bang, Kyunghye</creatorcontrib><creatorcontrib>Cheon, Jaekyung</creatorcontrib><creatorcontrib>Park, Young Soo</creatorcontrib><creatorcontrib>Kim, Hyung-Don</creatorcontrib><creatorcontrib>Ryu, Min-Hee</creatorcontrib><creatorcontrib>Park, Yangsoon</creatorcontrib><creatorcontrib>Moon, Meesun</creatorcontrib><creatorcontrib>Lee, Hyungeun</creatorcontrib><creatorcontrib>Kang, Yoon-Koo</creatorcontrib><title>Association between HER2 heterogeneity and clinical outcomes of HER2-positive gastric cancer patients treated with trastuzumab</title><title>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association</title><addtitle>Gastric Cancer</addtitle><addtitle>Gastric Cancer</addtitle><description>Background
The GASTHER1 study showed that re-evaluation of HER2 status rescued 8% of HER2-positive gastric cancer (GC) patients with initially HER2-negative GC. Since rescued HER2 positivity represents HER2 heterogeneity, we aimed to investigate this in a larger cohort with longer follow-up duration.
Methods
Data of 153 HER2-positive advanced GC patients who received first-line trastuzumab-based chemotherapy were analyzed. Repeat endoscopic biopsy was performed in patients with initially HER2-negative GC. Survival outcomes were analyzed according to the immunohistochemistry (IHC) score (IHC 2+ /in situ hybridization [ISH] + vs IHC 3+), HER2 status (initially vs rescued HER2 positive), and H-score.
Results
IHC 2+ /ISH + patients showed worse progression-free survival (PFS) and overall survival (OS) than those with IHC 3+ (
p
< 0.05). Rescued HER2-positive patients showed worse PFS and OS than initially HER2-positive patients (
p
< 0.05). Although survival outcomes were comparable according to HER2 status in IHC 2+ /ISH + patients, initially HER2-positive patients showed more favorable PFS and OS than rescued HER2-positive patients (
p
< 0.05) among those with IHC 3+ . Among the subgroups determined by HER2 status and IHC score, the initially IHC 3+ subgroup had the highest H-score. The low H-score group (H-score ≤ 210) had significantly worse survival outcomes than the high H-score group (H-score > 210) (
p
< 0.05). An H-score of ≤ 210 was independently associated with shorter OS (HR = 1.54, 95% CI 1.02–2.31,
p
= 0.04).
Conclusions
Rescued HER2-positive patients showed worse clinical outcomes than initially HER2-positive patients, especially those with IHC 3+ . This finding highlights the impact of HER2 heterogeneity, which can be quantified indirectly as an H-score.</description><subject>Abdominal Surgery</subject><subject>Biopsy</subject><subject>Cancer Research</subject><subject>Chemotherapy</subject><subject>Clinical outcomes</subject><subject>ErbB-2 protein</subject><subject>Gastric cancer</subject><subject>Gastroenterology</subject><subject>Hybridization</subject><subject>Immunohistochemistry</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Monoclonal antibodies</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Patients</subject><subject>Surgical Oncology</subject><subject>Survival</subject><subject>Targeted cancer therapy</subject><subject>Trastuzumab</subject><issn>1436-3291</issn><issn>1436-3305</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kctLHTEUh0NR6qP9B7ooATfdTM175i5FfBSEgug6ZDIn18hMcptkKrrwb2-8jxa6cJUTznd-58CH0BdKvlNC2tNMCWWkIYw1tVh0jfqADqngquGcyL1dzRb0AB3l_EgIlQuqPqIDLiUTXccP0etZztF6U3wMuIfyBBDw9cUtww9QIMUlBPDlGZswYDv64K0ZcZyLjRNkHN2abVYx--J_A16aXJK32JpgIeFVzYVQMi4JTIEBP_nyUD-Vml_myfSf0L4zY4bP2_cY3V9e3J1fNzc_r36cn900VgheGjs46wYQnRu4kYSCkbx10gkpKbfOcdX2g-25UIxIIpgbGO97x5RTXSdNy4_Rt03uKsVfM-SiJ58tjKMJEOesmVKUdFwIUtGT_9DHOKdQr6tUR1ir2jXFNpRNMecETq-Sn0x61pToNzt6Y0dXO3ptR6s69HUbPfcTDH9HdjoqwDdArq2whPRv9zuxfwBMxpw4</recordid><startdate>20220701</startdate><enddate>20220701</enddate><creator>Bang, Kyunghye</creator><creator>Cheon, Jaekyung</creator><creator>Park, Young Soo</creator><creator>Kim, Hyung-Don</creator><creator>Ryu, Min-Hee</creator><creator>Park, Yangsoon</creator><creator>Moon, Meesun</creator><creator>Lee, Hyungeun</creator><creator>Kang, Yoon-Koo</creator><general>Springer Nature Singapore</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0783-6583</orcidid></search><sort><creationdate>20220701</creationdate><title>Association between HER2 heterogeneity and clinical outcomes of HER2-positive gastric cancer patients treated with trastuzumab</title><author>Bang, Kyunghye ; Cheon, Jaekyung ; Park, Young Soo ; Kim, Hyung-Don ; Ryu, Min-Hee ; Park, Yangsoon ; Moon, Meesun ; Lee, Hyungeun ; Kang, Yoon-Koo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-cdfcfde48fd3a501ea537f5f45513cff367bdcb346205042fd23bbf26f6885a73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Abdominal Surgery</topic><topic>Biopsy</topic><topic>Cancer Research</topic><topic>Chemotherapy</topic><topic>Clinical outcomes</topic><topic>ErbB-2 protein</topic><topic>Gastric cancer</topic><topic>Gastroenterology</topic><topic>Hybridization</topic><topic>Immunohistochemistry</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Monoclonal antibodies</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Patients</topic><topic>Surgical Oncology</topic><topic>Survival</topic><topic>Targeted cancer therapy</topic><topic>Trastuzumab</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bang, Kyunghye</creatorcontrib><creatorcontrib>Cheon, Jaekyung</creatorcontrib><creatorcontrib>Park, Young Soo</creatorcontrib><creatorcontrib>Kim, Hyung-Don</creatorcontrib><creatorcontrib>Ryu, Min-Hee</creatorcontrib><creatorcontrib>Park, Yangsoon</creatorcontrib><creatorcontrib>Moon, Meesun</creatorcontrib><creatorcontrib>Lee, Hyungeun</creatorcontrib><creatorcontrib>Kang, Yoon-Koo</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bang, Kyunghye</au><au>Cheon, Jaekyung</au><au>Park, Young Soo</au><au>Kim, Hyung-Don</au><au>Ryu, Min-Hee</au><au>Park, Yangsoon</au><au>Moon, Meesun</au><au>Lee, Hyungeun</au><au>Kang, Yoon-Koo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association between HER2 heterogeneity and clinical outcomes of HER2-positive gastric cancer patients treated with trastuzumab</atitle><jtitle>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association</jtitle><stitle>Gastric Cancer</stitle><addtitle>Gastric Cancer</addtitle><date>2022-07-01</date><risdate>2022</risdate><volume>25</volume><issue>4</issue><spage>794</spage><epage>803</epage><pages>794-803</pages><issn>1436-3291</issn><eissn>1436-3305</eissn><abstract>Background
The GASTHER1 study showed that re-evaluation of HER2 status rescued 8% of HER2-positive gastric cancer (GC) patients with initially HER2-negative GC. Since rescued HER2 positivity represents HER2 heterogeneity, we aimed to investigate this in a larger cohort with longer follow-up duration.
Methods
Data of 153 HER2-positive advanced GC patients who received first-line trastuzumab-based chemotherapy were analyzed. Repeat endoscopic biopsy was performed in patients with initially HER2-negative GC. Survival outcomes were analyzed according to the immunohistochemistry (IHC) score (IHC 2+ /in situ hybridization [ISH] + vs IHC 3+), HER2 status (initially vs rescued HER2 positive), and H-score.
Results
IHC 2+ /ISH + patients showed worse progression-free survival (PFS) and overall survival (OS) than those with IHC 3+ (
p
< 0.05). Rescued HER2-positive patients showed worse PFS and OS than initially HER2-positive patients (
p
< 0.05). Although survival outcomes were comparable according to HER2 status in IHC 2+ /ISH + patients, initially HER2-positive patients showed more favorable PFS and OS than rescued HER2-positive patients (
p
< 0.05) among those with IHC 3+ . Among the subgroups determined by HER2 status and IHC score, the initially IHC 3+ subgroup had the highest H-score. The low H-score group (H-score ≤ 210) had significantly worse survival outcomes than the high H-score group (H-score > 210) (
p
< 0.05). An H-score of ≤ 210 was independently associated with shorter OS (HR = 1.54, 95% CI 1.02–2.31,
p
= 0.04).
Conclusions
Rescued HER2-positive patients showed worse clinical outcomes than initially HER2-positive patients, especially those with IHC 3+ . This finding highlights the impact of HER2 heterogeneity, which can be quantified indirectly as an H-score.</abstract><cop>Singapore</cop><pub>Springer Nature Singapore</pub><pmid>35524883</pmid><doi>10.1007/s10120-022-01298-6</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-0783-6583</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1436-3291 |
| ispartof | Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2022-07, Vol.25 (4), p.794-803 |
| issn | 1436-3291 1436-3305 |
| language | eng |
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| source | SpringerLink Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Abdominal Surgery Biopsy Cancer Research Chemotherapy Clinical outcomes ErbB-2 protein Gastric cancer Gastroenterology Hybridization Immunohistochemistry Medicine Medicine & Public Health Monoclonal antibodies Oncology Original Article Patients Surgical Oncology Survival Targeted cancer therapy Trastuzumab |
| title | Association between HER2 heterogeneity and clinical outcomes of HER2-positive gastric cancer patients treated with trastuzumab |
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