Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer
Introduction: Anti-HER2 antibody-drug conjugates (ADCs) have shown important efficacy in HER2-low metastatic breast cancer (mBC). Criteria for receiving ADCs are based on a single assay on the primary tumour or a small metastatic biopsy. We assessed the intra-patient inter-metastasis heterogeneity o...
Ausführliche Beschreibung
Autor*in: |
Geukens, Tatjana [verfasserIn] De Schepper, Maxim [verfasserIn] Richard, François [verfasserIn] Maetens, Marion [verfasserIn] Van Baelen, Karen [verfasserIn] Mahdami, Amena [verfasserIn] Nguyen, Ha-Linh [verfasserIn] Isnaldi, Edoardo [verfasserIn] Leduc, Sophia [verfasserIn] Pabba, Anirudh [verfasserIn] Zels, Gitte [verfasserIn] Mertens, Freya [verfasserIn] Vander Borght, Sara [verfasserIn] Smeets, Ann [verfasserIn] Nevelsteen, Ines [verfasserIn] Punie, Kevin [verfasserIn] Neven, Patrick [verfasserIn] Wildiers, Hans [verfasserIn] Van Den Bogaert, Wouter [verfasserIn] Floris, Giuseppe [verfasserIn] Desmedt, Christine [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2023 |
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Schlagwörter: |
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Übergeordnetes Werk: |
Enthalten in: European journal of cancer - Amsterdam [u.a.] : Elsevier, 1965, 188, Seite 152-160 |
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Übergeordnetes Werk: |
volume:188 ; pages:152-160 |
DOI / URN: |
10.1016/j.ejca.2023.04.026 |
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Katalog-ID: |
ELV010434054 |
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100 | 1 | |a Geukens, Tatjana |e verfasserin |0 (orcid)0000-0001-8828-8739 |4 aut | |
245 | 1 | 0 | |a Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer |
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520 | |a Introduction: Anti-HER2 antibody-drug conjugates (ADCs) have shown important efficacy in HER2-low metastatic breast cancer (mBC). Criteria for receiving ADCs are based on a single assay on the primary tumour or a small metastatic biopsy. We assessed the intra-patient inter-metastasis heterogeneity of HER2-low status in HER2-negative mBC.Patients and Methods: We included samples of 10 patients (7 ER-positive and 3 ER-negative) donated in the context of our post-mortem tissue donation program UPTIDER. Excisional post-mortem biopsies of 257 metastases and 8 breast tumours underwent central HER2 immunohistochemistry (IHC), alongside 41 pre-mortem primary or metastatic samples. They were classified as HER2-zero, HER2-low (HER2-1+ or HER2-2+, in situ hybridisation [ISH] negative) or HER2-positive (HER2-3+ or HER2-2+, ISH-positive) following ASCO/CAP guidelines 2018. HER2-zero was further subdivided into HER2-undetected (no staining) and HER2-ultralow (faint staining in ≤10% of tumour cells).Results: Median post-mortem interval was 2.5 h. In 8/10 patients, HER2-low and HER2-zero metastases co-existed, with the proportion of HER2-low lesions ranging from 5% to 89%. A total of 32% of metastases currently classified as HER2-zero were HER2-ultralow. Intra-organ inter-metastasis heterogeneity of HER2-scores was observed in the liver in 3/6 patients. Patients with primary ER-positive disease had a higher proportion of HER2-low metastases as compared to ER-negative disease (46% versus 8%, respectively). At the metastasis level, higher percentages of ER-expressing cells were observed in HER2-low or -ultralow as compared to HER2-undetected metastases.Conclusions: Important intra-patient inter-metastasis heterogeneity of HER2-low status exists. This questions the validity of HER2-low in its current form as a theranostic marker. | ||
650 | 4 | |a Breast cancer | |
650 | 4 | |a HER2-low | |
650 | 4 | |a Antibody-drug conjugate | |
650 | 4 | |a Metastasis | |
650 | 4 | |a Heterogeneity | |
700 | 1 | |a De Schepper, Maxim |e verfasserin |0 (orcid)0000-0001-9829-8535 |4 aut | |
700 | 1 | |a Richard, François |e verfasserin |0 (orcid)0000-0003-4353-3619 |4 aut | |
700 | 1 | |a Maetens, Marion |e verfasserin |4 aut | |
700 | 1 | |a Van Baelen, Karen |e verfasserin |0 (orcid)0000-0002-5700-3574 |4 aut | |
700 | 1 | |a Mahdami, Amena |e verfasserin |0 (orcid)0000-0002-3226-6933 |4 aut | |
700 | 1 | |a Nguyen, Ha-Linh |e verfasserin |0 (orcid)0000-0002-2538-7657 |4 aut | |
700 | 1 | |a Isnaldi, Edoardo |e verfasserin |4 aut | |
700 | 1 | |a Leduc, Sophia |e verfasserin |4 aut | |
700 | 1 | |a Pabba, Anirudh |e verfasserin |0 (orcid)0000-0003-2002-6956 |4 aut | |
700 | 1 | |a Zels, Gitte |e verfasserin |4 aut | |
700 | 1 | |a Mertens, Freya |e verfasserin |0 (orcid)0000-0003-2580-0496 |4 aut | |
700 | 1 | |a Vander Borght, Sara |e verfasserin |4 aut | |
700 | 1 | |a Smeets, Ann |e verfasserin |0 (orcid)0000-0002-5091-6602 |4 aut | |
700 | 1 | |a Nevelsteen, Ines |e verfasserin |4 aut | |
700 | 1 | |a Punie, Kevin |e verfasserin |0 (orcid)0000-0002-1162-7963 |4 aut | |
700 | 1 | |a Neven, Patrick |e verfasserin |4 aut | |
700 | 1 | |a Wildiers, Hans |e verfasserin |0 (orcid)0000-0001-8990-7837 |4 aut | |
700 | 1 | |a Van Den Bogaert, Wouter |e verfasserin |4 aut | |
700 | 1 | |a Floris, Giuseppe |e verfasserin |4 aut | |
700 | 1 | |a Desmedt, Christine |e verfasserin |0 (orcid)0000-0002-5223-5579 |4 aut | |
773 | 0 | 8 | |i Enthalten in |t European journal of cancer |d Amsterdam [u.a.] : Elsevier, 1965 |g 188, Seite 152-160 |w (DE-627)266883400 |w (DE-600)1468190-0 |w (DE-576)090954173 |x 1879-2995 |7 nnns |
773 | 1 | 8 | |g volume:188 |g pages:152-160 |
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10.1016/j.ejca.2023.04.026 doi (DE-627)ELV010434054 (ELSEVIER)S0959-8049(23)00227-7 DE-627 ger DE-627 rda eng 610 VZ 44.81 bkl Geukens, Tatjana verfasserin (orcid)0000-0001-8828-8739 aut Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction: Anti-HER2 antibody-drug conjugates (ADCs) have shown important efficacy in HER2-low metastatic breast cancer (mBC). Criteria for receiving ADCs are based on a single assay on the primary tumour or a small metastatic biopsy. We assessed the intra-patient inter-metastasis heterogeneity of HER2-low status in HER2-negative mBC.Patients and Methods: We included samples of 10 patients (7 ER-positive and 3 ER-negative) donated in the context of our post-mortem tissue donation program UPTIDER. Excisional post-mortem biopsies of 257 metastases and 8 breast tumours underwent central HER2 immunohistochemistry (IHC), alongside 41 pre-mortem primary or metastatic samples. They were classified as HER2-zero, HER2-low (HER2-1+ or HER2-2+, in situ hybridisation [ISH] negative) or HER2-positive (HER2-3+ or HER2-2+, ISH-positive) following ASCO/CAP guidelines 2018. HER2-zero was further subdivided into HER2-undetected (no staining) and HER2-ultralow (faint staining in ≤10% of tumour cells).Results: Median post-mortem interval was 2.5 h. In 8/10 patients, HER2-low and HER2-zero metastases co-existed, with the proportion of HER2-low lesions ranging from 5% to 89%. A total of 32% of metastases currently classified as HER2-zero were HER2-ultralow. Intra-organ inter-metastasis heterogeneity of HER2-scores was observed in the liver in 3/6 patients. Patients with primary ER-positive disease had a higher proportion of HER2-low metastases as compared to ER-negative disease (46% versus 8%, respectively). At the metastasis level, higher percentages of ER-expressing cells were observed in HER2-low or -ultralow as compared to HER2-undetected metastases.Conclusions: Important intra-patient inter-metastasis heterogeneity of HER2-low status exists. This questions the validity of HER2-low in its current form as a theranostic marker. Breast cancer HER2-low Antibody-drug conjugate Metastasis Heterogeneity De Schepper, Maxim verfasserin (orcid)0000-0001-9829-8535 aut Richard, François verfasserin (orcid)0000-0003-4353-3619 aut Maetens, Marion verfasserin aut Van Baelen, Karen verfasserin (orcid)0000-0002-5700-3574 aut Mahdami, Amena verfasserin (orcid)0000-0002-3226-6933 aut Nguyen, Ha-Linh verfasserin (orcid)0000-0002-2538-7657 aut Isnaldi, Edoardo verfasserin aut Leduc, Sophia verfasserin aut Pabba, Anirudh verfasserin (orcid)0000-0003-2002-6956 aut Zels, Gitte verfasserin aut Mertens, Freya verfasserin (orcid)0000-0003-2580-0496 aut Vander Borght, Sara verfasserin aut Smeets, Ann verfasserin (orcid)0000-0002-5091-6602 aut Nevelsteen, Ines verfasserin aut Punie, Kevin verfasserin (orcid)0000-0002-1162-7963 aut Neven, Patrick verfasserin aut Wildiers, Hans verfasserin (orcid)0000-0001-8990-7837 aut Van Den Bogaert, Wouter verfasserin aut Floris, Giuseppe verfasserin aut Desmedt, Christine verfasserin (orcid)0000-0002-5223-5579 aut Enthalten in European journal of cancer Amsterdam [u.a.] : Elsevier, 1965 188, Seite 152-160 (DE-627)266883400 (DE-600)1468190-0 (DE-576)090954173 1879-2995 nnns volume:188 pages:152-160 GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 Onkologie VZ AR 188 152-160 |
spelling |
10.1016/j.ejca.2023.04.026 doi (DE-627)ELV010434054 (ELSEVIER)S0959-8049(23)00227-7 DE-627 ger DE-627 rda eng 610 VZ 44.81 bkl Geukens, Tatjana verfasserin (orcid)0000-0001-8828-8739 aut Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction: Anti-HER2 antibody-drug conjugates (ADCs) have shown important efficacy in HER2-low metastatic breast cancer (mBC). Criteria for receiving ADCs are based on a single assay on the primary tumour or a small metastatic biopsy. We assessed the intra-patient inter-metastasis heterogeneity of HER2-low status in HER2-negative mBC.Patients and Methods: We included samples of 10 patients (7 ER-positive and 3 ER-negative) donated in the context of our post-mortem tissue donation program UPTIDER. Excisional post-mortem biopsies of 257 metastases and 8 breast tumours underwent central HER2 immunohistochemistry (IHC), alongside 41 pre-mortem primary or metastatic samples. They were classified as HER2-zero, HER2-low (HER2-1+ or HER2-2+, in situ hybridisation [ISH] negative) or HER2-positive (HER2-3+ or HER2-2+, ISH-positive) following ASCO/CAP guidelines 2018. HER2-zero was further subdivided into HER2-undetected (no staining) and HER2-ultralow (faint staining in ≤10% of tumour cells).Results: Median post-mortem interval was 2.5 h. In 8/10 patients, HER2-low and HER2-zero metastases co-existed, with the proportion of HER2-low lesions ranging from 5% to 89%. A total of 32% of metastases currently classified as HER2-zero were HER2-ultralow. Intra-organ inter-metastasis heterogeneity of HER2-scores was observed in the liver in 3/6 patients. Patients with primary ER-positive disease had a higher proportion of HER2-low metastases as compared to ER-negative disease (46% versus 8%, respectively). At the metastasis level, higher percentages of ER-expressing cells were observed in HER2-low or -ultralow as compared to HER2-undetected metastases.Conclusions: Important intra-patient inter-metastasis heterogeneity of HER2-low status exists. This questions the validity of HER2-low in its current form as a theranostic marker. Breast cancer HER2-low Antibody-drug conjugate Metastasis Heterogeneity De Schepper, Maxim verfasserin (orcid)0000-0001-9829-8535 aut Richard, François verfasserin (orcid)0000-0003-4353-3619 aut Maetens, Marion verfasserin aut Van Baelen, Karen verfasserin (orcid)0000-0002-5700-3574 aut Mahdami, Amena verfasserin (orcid)0000-0002-3226-6933 aut Nguyen, Ha-Linh verfasserin (orcid)0000-0002-2538-7657 aut Isnaldi, Edoardo verfasserin aut Leduc, Sophia verfasserin aut Pabba, Anirudh verfasserin (orcid)0000-0003-2002-6956 aut Zels, Gitte verfasserin aut Mertens, Freya verfasserin (orcid)0000-0003-2580-0496 aut Vander Borght, Sara verfasserin aut Smeets, Ann verfasserin (orcid)0000-0002-5091-6602 aut Nevelsteen, Ines verfasserin aut Punie, Kevin verfasserin (orcid)0000-0002-1162-7963 aut Neven, Patrick verfasserin aut Wildiers, Hans verfasserin (orcid)0000-0001-8990-7837 aut Van Den Bogaert, Wouter verfasserin aut Floris, Giuseppe verfasserin aut Desmedt, Christine verfasserin (orcid)0000-0002-5223-5579 aut Enthalten in European journal of cancer Amsterdam [u.a.] : Elsevier, 1965 188, Seite 152-160 (DE-627)266883400 (DE-600)1468190-0 (DE-576)090954173 1879-2995 nnns volume:188 pages:152-160 GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 Onkologie VZ AR 188 152-160 |
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10.1016/j.ejca.2023.04.026 doi (DE-627)ELV010434054 (ELSEVIER)S0959-8049(23)00227-7 DE-627 ger DE-627 rda eng 610 VZ 44.81 bkl Geukens, Tatjana verfasserin (orcid)0000-0001-8828-8739 aut Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction: Anti-HER2 antibody-drug conjugates (ADCs) have shown important efficacy in HER2-low metastatic breast cancer (mBC). Criteria for receiving ADCs are based on a single assay on the primary tumour or a small metastatic biopsy. We assessed the intra-patient inter-metastasis heterogeneity of HER2-low status in HER2-negative mBC.Patients and Methods: We included samples of 10 patients (7 ER-positive and 3 ER-negative) donated in the context of our post-mortem tissue donation program UPTIDER. Excisional post-mortem biopsies of 257 metastases and 8 breast tumours underwent central HER2 immunohistochemistry (IHC), alongside 41 pre-mortem primary or metastatic samples. They were classified as HER2-zero, HER2-low (HER2-1+ or HER2-2+, in situ hybridisation [ISH] negative) or HER2-positive (HER2-3+ or HER2-2+, ISH-positive) following ASCO/CAP guidelines 2018. HER2-zero was further subdivided into HER2-undetected (no staining) and HER2-ultralow (faint staining in ≤10% of tumour cells).Results: Median post-mortem interval was 2.5 h. In 8/10 patients, HER2-low and HER2-zero metastases co-existed, with the proportion of HER2-low lesions ranging from 5% to 89%. A total of 32% of metastases currently classified as HER2-zero were HER2-ultralow. Intra-organ inter-metastasis heterogeneity of HER2-scores was observed in the liver in 3/6 patients. Patients with primary ER-positive disease had a higher proportion of HER2-low metastases as compared to ER-negative disease (46% versus 8%, respectively). At the metastasis level, higher percentages of ER-expressing cells were observed in HER2-low or -ultralow as compared to HER2-undetected metastases.Conclusions: Important intra-patient inter-metastasis heterogeneity of HER2-low status exists. This questions the validity of HER2-low in its current form as a theranostic marker. Breast cancer HER2-low Antibody-drug conjugate Metastasis Heterogeneity De Schepper, Maxim verfasserin (orcid)0000-0001-9829-8535 aut Richard, François verfasserin (orcid)0000-0003-4353-3619 aut Maetens, Marion verfasserin aut Van Baelen, Karen verfasserin (orcid)0000-0002-5700-3574 aut Mahdami, Amena verfasserin (orcid)0000-0002-3226-6933 aut Nguyen, Ha-Linh verfasserin (orcid)0000-0002-2538-7657 aut Isnaldi, Edoardo verfasserin aut Leduc, Sophia verfasserin aut Pabba, Anirudh verfasserin (orcid)0000-0003-2002-6956 aut Zels, Gitte verfasserin aut Mertens, Freya verfasserin (orcid)0000-0003-2580-0496 aut Vander Borght, Sara verfasserin aut Smeets, Ann verfasserin (orcid)0000-0002-5091-6602 aut Nevelsteen, Ines verfasserin aut Punie, Kevin verfasserin (orcid)0000-0002-1162-7963 aut Neven, Patrick verfasserin aut Wildiers, Hans verfasserin (orcid)0000-0001-8990-7837 aut Van Den Bogaert, Wouter verfasserin aut Floris, Giuseppe verfasserin aut Desmedt, Christine verfasserin (orcid)0000-0002-5223-5579 aut Enthalten in European journal of cancer Amsterdam [u.a.] : Elsevier, 1965 188, Seite 152-160 (DE-627)266883400 (DE-600)1468190-0 (DE-576)090954173 1879-2995 nnns volume:188 pages:152-160 GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 Onkologie VZ AR 188 152-160 |
allfieldsGer |
10.1016/j.ejca.2023.04.026 doi (DE-627)ELV010434054 (ELSEVIER)S0959-8049(23)00227-7 DE-627 ger DE-627 rda eng 610 VZ 44.81 bkl Geukens, Tatjana verfasserin (orcid)0000-0001-8828-8739 aut Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction: Anti-HER2 antibody-drug conjugates (ADCs) have shown important efficacy in HER2-low metastatic breast cancer (mBC). Criteria for receiving ADCs are based on a single assay on the primary tumour or a small metastatic biopsy. We assessed the intra-patient inter-metastasis heterogeneity of HER2-low status in HER2-negative mBC.Patients and Methods: We included samples of 10 patients (7 ER-positive and 3 ER-negative) donated in the context of our post-mortem tissue donation program UPTIDER. Excisional post-mortem biopsies of 257 metastases and 8 breast tumours underwent central HER2 immunohistochemistry (IHC), alongside 41 pre-mortem primary or metastatic samples. They were classified as HER2-zero, HER2-low (HER2-1+ or HER2-2+, in situ hybridisation [ISH] negative) or HER2-positive (HER2-3+ or HER2-2+, ISH-positive) following ASCO/CAP guidelines 2018. HER2-zero was further subdivided into HER2-undetected (no staining) and HER2-ultralow (faint staining in ≤10% of tumour cells).Results: Median post-mortem interval was 2.5 h. In 8/10 patients, HER2-low and HER2-zero metastases co-existed, with the proportion of HER2-low lesions ranging from 5% to 89%. A total of 32% of metastases currently classified as HER2-zero were HER2-ultralow. Intra-organ inter-metastasis heterogeneity of HER2-scores was observed in the liver in 3/6 patients. Patients with primary ER-positive disease had a higher proportion of HER2-low metastases as compared to ER-negative disease (46% versus 8%, respectively). At the metastasis level, higher percentages of ER-expressing cells were observed in HER2-low or -ultralow as compared to HER2-undetected metastases.Conclusions: Important intra-patient inter-metastasis heterogeneity of HER2-low status exists. This questions the validity of HER2-low in its current form as a theranostic marker. Breast cancer HER2-low Antibody-drug conjugate Metastasis Heterogeneity De Schepper, Maxim verfasserin (orcid)0000-0001-9829-8535 aut Richard, François verfasserin (orcid)0000-0003-4353-3619 aut Maetens, Marion verfasserin aut Van Baelen, Karen verfasserin (orcid)0000-0002-5700-3574 aut Mahdami, Amena verfasserin (orcid)0000-0002-3226-6933 aut Nguyen, Ha-Linh verfasserin (orcid)0000-0002-2538-7657 aut Isnaldi, Edoardo verfasserin aut Leduc, Sophia verfasserin aut Pabba, Anirudh verfasserin (orcid)0000-0003-2002-6956 aut Zels, Gitte verfasserin aut Mertens, Freya verfasserin (orcid)0000-0003-2580-0496 aut Vander Borght, Sara verfasserin aut Smeets, Ann verfasserin (orcid)0000-0002-5091-6602 aut Nevelsteen, Ines verfasserin aut Punie, Kevin verfasserin (orcid)0000-0002-1162-7963 aut Neven, Patrick verfasserin aut Wildiers, Hans verfasserin (orcid)0000-0001-8990-7837 aut Van Den Bogaert, Wouter verfasserin aut Floris, Giuseppe verfasserin aut Desmedt, Christine verfasserin (orcid)0000-0002-5223-5579 aut Enthalten in European journal of cancer Amsterdam [u.a.] : Elsevier, 1965 188, Seite 152-160 (DE-627)266883400 (DE-600)1468190-0 (DE-576)090954173 1879-2995 nnns volume:188 pages:152-160 GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 Onkologie VZ AR 188 152-160 |
allfieldsSound |
10.1016/j.ejca.2023.04.026 doi (DE-627)ELV010434054 (ELSEVIER)S0959-8049(23)00227-7 DE-627 ger DE-627 rda eng 610 VZ 44.81 bkl Geukens, Tatjana verfasserin (orcid)0000-0001-8828-8739 aut Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction: Anti-HER2 antibody-drug conjugates (ADCs) have shown important efficacy in HER2-low metastatic breast cancer (mBC). Criteria for receiving ADCs are based on a single assay on the primary tumour or a small metastatic biopsy. We assessed the intra-patient inter-metastasis heterogeneity of HER2-low status in HER2-negative mBC.Patients and Methods: We included samples of 10 patients (7 ER-positive and 3 ER-negative) donated in the context of our post-mortem tissue donation program UPTIDER. Excisional post-mortem biopsies of 257 metastases and 8 breast tumours underwent central HER2 immunohistochemistry (IHC), alongside 41 pre-mortem primary or metastatic samples. They were classified as HER2-zero, HER2-low (HER2-1+ or HER2-2+, in situ hybridisation [ISH] negative) or HER2-positive (HER2-3+ or HER2-2+, ISH-positive) following ASCO/CAP guidelines 2018. HER2-zero was further subdivided into HER2-undetected (no staining) and HER2-ultralow (faint staining in ≤10% of tumour cells).Results: Median post-mortem interval was 2.5 h. In 8/10 patients, HER2-low and HER2-zero metastases co-existed, with the proportion of HER2-low lesions ranging from 5% to 89%. A total of 32% of metastases currently classified as HER2-zero were HER2-ultralow. Intra-organ inter-metastasis heterogeneity of HER2-scores was observed in the liver in 3/6 patients. Patients with primary ER-positive disease had a higher proportion of HER2-low metastases as compared to ER-negative disease (46% versus 8%, respectively). At the metastasis level, higher percentages of ER-expressing cells were observed in HER2-low or -ultralow as compared to HER2-undetected metastases.Conclusions: Important intra-patient inter-metastasis heterogeneity of HER2-low status exists. This questions the validity of HER2-low in its current form as a theranostic marker. Breast cancer HER2-low Antibody-drug conjugate Metastasis Heterogeneity De Schepper, Maxim verfasserin (orcid)0000-0001-9829-8535 aut Richard, François verfasserin (orcid)0000-0003-4353-3619 aut Maetens, Marion verfasserin aut Van Baelen, Karen verfasserin (orcid)0000-0002-5700-3574 aut Mahdami, Amena verfasserin (orcid)0000-0002-3226-6933 aut Nguyen, Ha-Linh verfasserin (orcid)0000-0002-2538-7657 aut Isnaldi, Edoardo verfasserin aut Leduc, Sophia verfasserin aut Pabba, Anirudh verfasserin (orcid)0000-0003-2002-6956 aut Zels, Gitte verfasserin aut Mertens, Freya verfasserin (orcid)0000-0003-2580-0496 aut Vander Borght, Sara verfasserin aut Smeets, Ann verfasserin (orcid)0000-0002-5091-6602 aut Nevelsteen, Ines verfasserin aut Punie, Kevin verfasserin (orcid)0000-0002-1162-7963 aut Neven, Patrick verfasserin aut Wildiers, Hans verfasserin (orcid)0000-0001-8990-7837 aut Van Den Bogaert, Wouter verfasserin aut Floris, Giuseppe verfasserin aut Desmedt, Christine verfasserin (orcid)0000-0002-5223-5579 aut Enthalten in European journal of cancer Amsterdam [u.a.] : Elsevier, 1965 188, Seite 152-160 (DE-627)266883400 (DE-600)1468190-0 (DE-576)090954173 1879-2995 nnns volume:188 pages:152-160 GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 Onkologie VZ AR 188 152-160 |
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Enthalten in European journal of cancer 188, Seite 152-160 volume:188 pages:152-160 |
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Enthalten in European journal of cancer 188, Seite 152-160 volume:188 pages:152-160 |
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Breast cancer HER2-low Antibody-drug conjugate Metastasis Heterogeneity |
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European journal of cancer |
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Geukens, Tatjana @@aut@@ De Schepper, Maxim @@aut@@ Richard, François @@aut@@ Maetens, Marion @@aut@@ Van Baelen, Karen @@aut@@ Mahdami, Amena @@aut@@ Nguyen, Ha-Linh @@aut@@ Isnaldi, Edoardo @@aut@@ Leduc, Sophia @@aut@@ Pabba, Anirudh @@aut@@ Zels, Gitte @@aut@@ Mertens, Freya @@aut@@ Vander Borght, Sara @@aut@@ Smeets, Ann @@aut@@ Nevelsteen, Ines @@aut@@ Punie, Kevin @@aut@@ Neven, Patrick @@aut@@ Wildiers, Hans @@aut@@ Van Den Bogaert, Wouter @@aut@@ Floris, Giuseppe @@aut@@ Desmedt, Christine @@aut@@ |
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2023-01-01T00:00:00Z |
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Criteria for receiving ADCs are based on a single assay on the primary tumour or a small metastatic biopsy. We assessed the intra-patient inter-metastasis heterogeneity of HER2-low status in HER2-negative mBC.Patients and Methods: We included samples of 10 patients (7 ER-positive and 3 ER-negative) donated in the context of our post-mortem tissue donation program UPTIDER. Excisional post-mortem biopsies of 257 metastases and 8 breast tumours underwent central HER2 immunohistochemistry (IHC), alongside 41 pre-mortem primary or metastatic samples. They were classified as HER2-zero, HER2-low (HER2-1+ or HER2-2+, in situ hybridisation [ISH] negative) or HER2-positive (HER2-3+ or HER2-2+, ISH-positive) following ASCO/CAP guidelines 2018. HER2-zero was further subdivided into HER2-undetected (no staining) and HER2-ultralow (faint staining in ≤10% of tumour cells).Results: Median post-mortem interval was 2.5 h. In 8/10 patients, HER2-low and HER2-zero metastases co-existed, with the proportion of HER2-low lesions ranging from 5% to 89%. A total of 32% of metastases currently classified as HER2-zero were HER2-ultralow. Intra-organ inter-metastasis heterogeneity of HER2-scores was observed in the liver in 3/6 patients. Patients with primary ER-positive disease had a higher proportion of HER2-low metastases as compared to ER-negative disease (46% versus 8%, respectively). At the metastasis level, higher percentages of ER-expressing cells were observed in HER2-low or -ultralow as compared to HER2-undetected metastases.Conclusions: Important intra-patient inter-metastasis heterogeneity of HER2-low status exists. 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|
author |
Geukens, Tatjana |
spellingShingle |
Geukens, Tatjana ddc 610 bkl 44.81 misc Breast cancer misc HER2-low misc Antibody-drug conjugate misc Metastasis misc Heterogeneity Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer |
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610 VZ 44.81 bkl Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer Breast cancer HER2-low Antibody-drug conjugate Metastasis Heterogeneity |
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ddc 610 bkl 44.81 misc Breast cancer misc HER2-low misc Antibody-drug conjugate misc Metastasis misc Heterogeneity |
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Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer |
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(DE-627)ELV010434054 (ELSEVIER)S0959-8049(23)00227-7 |
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Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer |
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Geukens, Tatjana |
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European journal of cancer |
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European journal of cancer |
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Geukens, Tatjana De Schepper, Maxim Richard, François Maetens, Marion Van Baelen, Karen Mahdami, Amena Nguyen, Ha-Linh Isnaldi, Edoardo Leduc, Sophia Pabba, Anirudh Zels, Gitte Mertens, Freya Vander Borght, Sara Smeets, Ann Nevelsteen, Ines Punie, Kevin Neven, Patrick Wildiers, Hans Van Den Bogaert, Wouter Floris, Giuseppe Desmedt, Christine |
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10.1016/j.ejca.2023.04.026 |
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(ORCID)0000-0001-8828-8739 (ORCID)0000-0001-9829-8535 (ORCID)0000-0003-4353-3619 (ORCID)0000-0002-5700-3574 (ORCID)0000-0002-3226-6933 (ORCID)0000-0002-2538-7657 (ORCID)0000-0003-2002-6956 (ORCID)0000-0003-2580-0496 (ORCID)0000-0002-5091-6602 (ORCID)0000-0002-1162-7963 (ORCID)0000-0001-8990-7837 (ORCID)0000-0002-5223-5579 |
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intra-patient and inter-metastasis heterogeneity of her2-low status in metastatic breast cancer |
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Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer |
abstract |
Introduction: Anti-HER2 antibody-drug conjugates (ADCs) have shown important efficacy in HER2-low metastatic breast cancer (mBC). Criteria for receiving ADCs are based on a single assay on the primary tumour or a small metastatic biopsy. We assessed the intra-patient inter-metastasis heterogeneity of HER2-low status in HER2-negative mBC.Patients and Methods: We included samples of 10 patients (7 ER-positive and 3 ER-negative) donated in the context of our post-mortem tissue donation program UPTIDER. Excisional post-mortem biopsies of 257 metastases and 8 breast tumours underwent central HER2 immunohistochemistry (IHC), alongside 41 pre-mortem primary or metastatic samples. They were classified as HER2-zero, HER2-low (HER2-1+ or HER2-2+, in situ hybridisation [ISH] negative) or HER2-positive (HER2-3+ or HER2-2+, ISH-positive) following ASCO/CAP guidelines 2018. HER2-zero was further subdivided into HER2-undetected (no staining) and HER2-ultralow (faint staining in ≤10% of tumour cells).Results: Median post-mortem interval was 2.5 h. In 8/10 patients, HER2-low and HER2-zero metastases co-existed, with the proportion of HER2-low lesions ranging from 5% to 89%. A total of 32% of metastases currently classified as HER2-zero were HER2-ultralow. Intra-organ inter-metastasis heterogeneity of HER2-scores was observed in the liver in 3/6 patients. Patients with primary ER-positive disease had a higher proportion of HER2-low metastases as compared to ER-negative disease (46% versus 8%, respectively). At the metastasis level, higher percentages of ER-expressing cells were observed in HER2-low or -ultralow as compared to HER2-undetected metastases.Conclusions: Important intra-patient inter-metastasis heterogeneity of HER2-low status exists. This questions the validity of HER2-low in its current form as a theranostic marker. |
abstractGer |
Introduction: Anti-HER2 antibody-drug conjugates (ADCs) have shown important efficacy in HER2-low metastatic breast cancer (mBC). Criteria for receiving ADCs are based on a single assay on the primary tumour or a small metastatic biopsy. We assessed the intra-patient inter-metastasis heterogeneity of HER2-low status in HER2-negative mBC.Patients and Methods: We included samples of 10 patients (7 ER-positive and 3 ER-negative) donated in the context of our post-mortem tissue donation program UPTIDER. Excisional post-mortem biopsies of 257 metastases and 8 breast tumours underwent central HER2 immunohistochemistry (IHC), alongside 41 pre-mortem primary or metastatic samples. They were classified as HER2-zero, HER2-low (HER2-1+ or HER2-2+, in situ hybridisation [ISH] negative) or HER2-positive (HER2-3+ or HER2-2+, ISH-positive) following ASCO/CAP guidelines 2018. HER2-zero was further subdivided into HER2-undetected (no staining) and HER2-ultralow (faint staining in ≤10% of tumour cells).Results: Median post-mortem interval was 2.5 h. In 8/10 patients, HER2-low and HER2-zero metastases co-existed, with the proportion of HER2-low lesions ranging from 5% to 89%. A total of 32% of metastases currently classified as HER2-zero were HER2-ultralow. Intra-organ inter-metastasis heterogeneity of HER2-scores was observed in the liver in 3/6 patients. Patients with primary ER-positive disease had a higher proportion of HER2-low metastases as compared to ER-negative disease (46% versus 8%, respectively). At the metastasis level, higher percentages of ER-expressing cells were observed in HER2-low or -ultralow as compared to HER2-undetected metastases.Conclusions: Important intra-patient inter-metastasis heterogeneity of HER2-low status exists. This questions the validity of HER2-low in its current form as a theranostic marker. |
abstract_unstemmed |
Introduction: Anti-HER2 antibody-drug conjugates (ADCs) have shown important efficacy in HER2-low metastatic breast cancer (mBC). Criteria for receiving ADCs are based on a single assay on the primary tumour or a small metastatic biopsy. We assessed the intra-patient inter-metastasis heterogeneity of HER2-low status in HER2-negative mBC.Patients and Methods: We included samples of 10 patients (7 ER-positive and 3 ER-negative) donated in the context of our post-mortem tissue donation program UPTIDER. Excisional post-mortem biopsies of 257 metastases and 8 breast tumours underwent central HER2 immunohistochemistry (IHC), alongside 41 pre-mortem primary or metastatic samples. They were classified as HER2-zero, HER2-low (HER2-1+ or HER2-2+, in situ hybridisation [ISH] negative) or HER2-positive (HER2-3+ or HER2-2+, ISH-positive) following ASCO/CAP guidelines 2018. HER2-zero was further subdivided into HER2-undetected (no staining) and HER2-ultralow (faint staining in ≤10% of tumour cells).Results: Median post-mortem interval was 2.5 h. In 8/10 patients, HER2-low and HER2-zero metastases co-existed, with the proportion of HER2-low lesions ranging from 5% to 89%. A total of 32% of metastases currently classified as HER2-zero were HER2-ultralow. Intra-organ inter-metastasis heterogeneity of HER2-scores was observed in the liver in 3/6 patients. Patients with primary ER-positive disease had a higher proportion of HER2-low metastases as compared to ER-negative disease (46% versus 8%, respectively). At the metastasis level, higher percentages of ER-expressing cells were observed in HER2-low or -ultralow as compared to HER2-undetected metastases.Conclusions: Important intra-patient inter-metastasis heterogeneity of HER2-low status exists. This questions the validity of HER2-low in its current form as a theranostic marker. |
collection_details |
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title_short |
Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer |
remote_bool |
true |
author2 |
De Schepper, Maxim Richard, François Maetens, Marion Van Baelen, Karen Mahdami, Amena Nguyen, Ha-Linh Isnaldi, Edoardo Leduc, Sophia Pabba, Anirudh Zels, Gitte Mertens, Freya Vander Borght, Sara Smeets, Ann Nevelsteen, Ines Punie, Kevin Neven, Patrick Wildiers, Hans Van Den Bogaert, Wouter Floris, Giuseppe Desmedt, Christine |
author2Str |
De Schepper, Maxim Richard, François Maetens, Marion Van Baelen, Karen Mahdami, Amena Nguyen, Ha-Linh Isnaldi, Edoardo Leduc, Sophia Pabba, Anirudh Zels, Gitte Mertens, Freya Vander Borght, Sara Smeets, Ann Nevelsteen, Ines Punie, Kevin Neven, Patrick Wildiers, Hans Van Den Bogaert, Wouter Floris, Giuseppe Desmedt, Christine |
ppnlink |
266883400 |
mediatype_str_mv |
c |
isOA_txt |
false |
hochschulschrift_bool |
false |
doi_str |
10.1016/j.ejca.2023.04.026 |
up_date |
2024-07-06T17:58:40.758Z |
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1803853465660686336 |
fullrecord_marcxml |
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|
score |
7.40158 |