A Comprehensive Review on the Role of Human Epidermal Growth Factor Receptor 2 (HER2) as a Biomarker in Extra-Mammary and Extra-Gastric Cancers
Abstract
:Simple Summary
Abstract
1. Introduction
1.1. Nomenclature, Structure and Function
1.2. Testing for HER2 Neu
2. Strategies for Review
3. Results
3.1. Ovarian Cancer
3.2. Endometrial Cancer
3.3. Lung Cancer
3.4. Colorectal Cancer (CRC)
3.5. Salivary Gland Cancer
3.6. Pancreatic Cancer
3.7. Bladder Cancer
3.8. Prostate Cancer
3.9. Biliary Tract Cancer (BTC)
3.10. Other Malignancies
3.10.1. Osteosarcoma (OS)
3.10.2. Thyroid Cancer
3.10.3. Glioblastoma Multiforme (GBM)
3.10.4. Acute Lymphoblastic Leukemia (ALL)
3.10.5. Soft Tissue Sarcoma
3.10.6. Wilms Tumor
3.10.7. Melanoma
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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IHC Score | Result | Staining Pattern | Percentage Of Stained Cells |
---|---|---|---|
0 | Negative | Absent staining | 0 |
1+ | Negative | Faint or weak incomplete staining | <10% |
2+ | Equivocal | Thin circumferential membrane staining or heterogeneity in staining distribution | >10% but < 30% |
3+ | Positive | Diffuse intense circumferential membrane “chicken-wire” | >30% |
Name of the Study | Number of Patients | Protein Overexpression (%) | Amplification (%) |
---|---|---|---|
Rubin SC et al., 1994 [19] | 40 | 20 | - |
Seki A et al., 2000 [20] | 48 | - | 25 |
Gao D et al., 2002 [21] | 54 | 25.9 | - |
Hogdall et al., 2003 [22] | 181 | 13.3 | - |
Bookman MA et al., 2003 [23] | 837 | 11.4 | - |
Camilleri-Broet et al., 2004 [24] | 95 | 15.8 | - |
Mano MS et al., 2004 [25] | 64 | - | 12.5 |
Lee CH et al., 2005 [26] | 102 | 4.9 | 2 |
Tuefferd M et al., 2007 [27] | 320 | 12.8 | 6.6 |
Sasaki N et al., 2007 [28] | 141 | 12.8 | - |
Sueblinvong et al., 2007 [29] | 74 | 10.2 | - |
Stefensen KD et al., 2008 [30] | 99 | 14.1 | - |
Vermeij et al., 2008 [31] | 52 | 35 | 10 |
Farley J et al., 2009 [32] | 133 | - | 6.8 |
Chekerov R et al., 2009 [33] | 50 | 52 | - |
Slyvia MT et al., 2012 [34] | 60 | 21 | - |
Jafri A et al., 2017 [35] | 56 | 37.5 | - |
Pankaj S et al., 2019 [36] | 98 | 22.45 | - |
Clinical Trial | Study Description | Indication | PEP and Treatment Arms | Outcomes |
---|---|---|---|---|
1. Bookman MA et al., 2003 [23] | Single arm, Phase II, N = 95 | HER2 2+ or 3+ overexpressing refractory epithelial ovarian or primary peritoneal cancer | ORR and Trastuzumab |
|
2. Makhija S et al., 2010 [37] | Phase II, Randomized, N = 130 | Advanced, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received a maximum of one prior treatment for recurrent cancer | Safety/PFS and Pertuzumab + Gemcitabine vs. Gemcitabine |
|
Name of the Study | Number of Patients | Protein Overexpression (%) | Amplification (%) |
---|---|---|---|
Santin AD et al., 2002 [44] | 10 | 80 | - |
Solomovitz BM et al., 2004 [45] | 68 | 18 | 2.9 |
Santin AD et al., 2005 [46] | 30 | - | 47 |
Santin AS et al., 2005 [43] | 26 | 62 | 42 |
Diaz-Montes TP et al., 2006 [47] | 25 | 48 | - |
Villella JA et al., 2006 [48] | 19 | 26 | - |
Odicino FE et al., 2008 [49] | 12 | 16.6 | 16.6 |
Ren Y et al., 2011 [50] | 36 | 36.1 | 11.1 |
Togami S et al., 2012 [51] | 71 | 14 | - |
Banet et al., 2021 [52] | 68 | 9 | - |
Clinical Trial | Study Description | Indication | PEP and Treatment Arms | Outcomes |
---|---|---|---|---|
1. Fleming GF et al., 2009, [53] | Single arm, Phase II, N = 34 | Stage III, IV or recurrent endometrial carcinoma with either 2+/3+ HER2 overexpression or gene amplification | ORR and Trastuzumab |
|
2.Tymon-Rosario J et al., 2021 [54] | Multi-center, Phase II, N = 60 | Recurrent/Advanced (Stage III–IV) HER2/neu overexpressing uterine serous carcinoma | PFS and Carboplatin/Paclitaxel +Trastuzumab vs. Carboplatin/Paclitaxel alone |
|
Name of the Study | Number of Patients | Mutations (%) |
---|---|---|
Shingematsu, H.I. et al., 2005 [59] | 671 | 2.6 |
Buttitta, F.L. et al., 2006 [70] | 403 | 2.2 |
Sasaki, Y. et al., 2006 [71] | 122 | 0.8 |
Sun, Y. et al., 2010 [72] | 52 | 3.8 |
Tomizawa, K. et al., 2011 [73] | 504 | 2.6 |
Li, C. et al., 2012 [74] | 224 | 3.6 |
Arcila, M. et al., 2012 [75] | 1478 | 1.7 |
Mazieres, J.I. et al., 2013 [76] | 3800 | 1.7 |
Clinical Trial, Study Description | Study Description | Indication | PEP and Treatment Arms | Outcomes |
---|---|---|---|---|
1. Cappuzzo, F. et al., 2003 [77] | Phase II, N = 63 | Advanced NSCLC | TP and Gefitinib |
|
2. Langer, C.J. et al., 2004 [78] | Phase II, N = 56 | HER2 overexpressing advanced NSCLC | OS and Trastuzumab + Paclitaxel + Carboplatin |
|
3. Gatzemeier, U. et al., 2004 [61] | Phase II Randomized, N= 103 | Untreated stage IIIB/IV HER2-positive NSCLC | ORR and Trastuzumab + Cisplatin + gemcitabine vs. Cisplatin + gemcitabine alone |
|
4. Zinner, R.G. et al., 2004 [62] | Phase II, N = 21 | HER2-overexpressing (IHC >1+ or HER2 neu antigen in serum) stages IIIB or IV NSCLC | ORR and Trastuzumab + cisplatin +Gemcitabine | 8 (38%) patients had a partial response
|
5. Lara, P.N., Jr. et al., 2004 [63] | Phase II, N = 13 | Advanced NSCLC in which primary platinum-based therapy had failed | Screening for HER2, ORR and Single agent Trastuzumab or docetaxel followed by combination Trastuzumab + Docetaxel |
|
6. Clamon, G. et al., 2005 [79] | Phase II, N = 29 | Stage IIIB or Stage IV NSCLC with 2+/3+ HER2 expression with at least 1 prior chemotherapy regimen. | Screening for HER2, ORR Single agent Trastuzumab |
|
7. Krug, L.M. et al., 2005 [80] | Phase II, Randomized, N = 169 | Previously untreated advanced NSCLC | ORR and Trastuzumab + Docetaxel or Trastuzumab + Paclitaxel |
|
8. Kris, M.G. et al., 2015 [67] | Phase II, N = 30 | Stage IIIB/IV lung cancers with HER2 mutations in exon 20 or amplification. | PRS, OS, toxicity and Dacomitinib |
|
9. Li, B.T. et al., 2018 [64] | Phase II, N = 18 | HER2 mutant lung adenocarcinomas | ORR and Ado-Trastuzumab emastine |
|
10. De Langen, A.J. et al., 2018 [81] | Phase II, N = 24 | NSCLC with a sensitizing EGFR mutation who show HER2 expression after progression on EGFR TKI treatment | ORR and Trastuzumab + Paclitaxel |
|
11. Peters, S. et al., 2019 [65] | Phase II, N = 49 | HER2-overexpressing advanced NSCLC who have received previous platinum-based chemotherapy and targeted therapy in the case of EGFR mutation or ALK gene rearrangement | ORR and Ado-Trastuzumab emastine |
|
12. ETOP TRIAL, Dziadziuszko et al., 2019 [68] | Phase II, N = 13 | Pretreated advanced NSCLC harboring HER2 exon 20 mutations | ORR and Afatinib |
|
13. Fan, Y. et al., 2020 [69] | Phase II, N = 18 | HER2 mutation positive Stage IIIB/IV non-small cell lung cancer had failed one or two prior lines of chemotherapy and were EGFR/HER2-inhibitor naïve. | ORR and Afatinib followed by Afatinib + Paclitaxel |
|
14. DESTINYLUNG01 TRIAL (NCT03505710) 2022 [66] | Phase II, N = 91 | HER2 mutant metastatic NSCLC refractory to standard treatment | ORR and Trastuzumab Deruxtecan |
|
Name of the Study | Number of Patients | Protein Overexpression (%) | Amplification (%) |
---|---|---|---|
Rossi, H. et al., 2002 [91] | 156 | 24 | - |
Knosel, T. et al., 2002 [92] | 74 | 51 | - |
Nathanson, D.R. et al., 2003 [93] | 139–169 | 3.6 (5/139) | 2.4 (4/169) |
Park, D.I. et al., 2004 [56] | 88 | 12.5 | - |
Schuell, B. et al., 2006 [94] | 77 | 3.8 | - |
Kountourakis, P. et al., 2006 [95] | 106 | 5.6 | - |
Park, D.I. et al., 2007 [96] | 137 | 47.4 | 1.4 |
Ismail, H.M. et al., 2007 [97] | 104 | 9.6 | - |
Kavanagh, D.O., 2009 [98] | 132 | 11 | 3 |
Marx, A.H. et al., 2010 [99] | 1439 | 2.5 | 2.7 |
Li, Q. et al., 2011 [100] | 317 | 15.5 | - |
Herreros Villanaueva, M. et al., 2011 [101] | 186 | - | 26.3 |
Pappas, A. et al., 2013 [102] | 51 | 3.9 | - |
Shabbir, A. et al., 2016 [83] | 95 | 78.9 | - |
Kwak, Y. et al., 2017 [103] | 334 | - | 6 |
Ross, J.S. et al., 2018 [104] | 8887 | - | 58.5 |
Hasan, R. et al., 2018 [105] | 83 | 40.96 | - |
Richman et al., 2019 [106] | 3256 | 1.6 | 1.4 |
Clinical Trial | Study Description | Indication | PEP and Treatment Arms | Outcomes |
---|---|---|---|---|
1. Ramanathan, R.K. et al., 2014 [107] | Phase II, N = 9 | HER2 overexpressing advanced CRC | HER2 expression rate, MTD and Trastuzumab + Irinotecan |
|
2. Rubinson, D.A. et al., 2014 [86] | Open label, Multi-center Phase I/II, N = 13 | Metastatic colorectal cancer with cetuximab resistance | Dose-limiting toxicity and Pertuzumab + cetuximab |
|
3. HERCALESA TRIAL, 2016 [87] | Multi-center, Open label, Phase II, N = 27 | KRAS exon 2 (codons 12 and 13) wild-type and HER2-positive metastatic colorectal cancer refractory to standard of care (including cetuximab or panitumumab) | ORR and Trastuzumab + lapatinib |
|
4. MY PATHWAY TRIAL (NCT02091141) 2019 [88] | Phase IIA, Multiple Basket, N = 57 | Refractory, histologically confirmed HER2-amplified metastatic colorectal cancer | ORR and Trastuzumab +Pertuzumab |
|
5. HERACLESB TRIAL (NCT03225937) 2020 [89] | Single arm, Phase II, N = 31 | Histologically confirmed RAS/BRAF wild-type and HER2+ metastatic CRC refractory to standard treatments | ORR and Trastuzumab emtansine +Pertuzumab |
|
6. DESTINYCRC01 TRIAL (NCT03384940) 2021 [90] | Open label, Multi-center, Phase II, N = 78 | HER-positive metastatic colorectal cancer that had progressed on two or more previous regimens (HER2-targeted therapies other than trastuzumab deruxtecan permitted) | ORR and Trastuzumab deruxtecan vs. standard treatment |
|
Name of the Study | Histology | Number of Patients | Protein Overexpression (%) | Amplification (%) |
---|---|---|---|---|
Press, M.F. et al., 1994 [114] | Mucoepidermoid carcinoma | 58 | 38 | 21 |
Skalova et al., 2001 [115] | SDC | 15 | 93.3 | - |
Skalova, A. et al., 2003 [116] | SDC | 11 | 100 | 36.4 |
Erges, A. et al., 2003 [117] | SDC | 5 | 80 | - |
Jaehne et al., 2005 [118] | SDC | 50 | 20.6 | - |
Cornolti, G. et al., 2007 [119] | SDC | 13 | 10/13 | 8/10 |
Johnson, C.J. et al., 2008 [120] | SDC | 12 | 33.3 | 33.3 |
Santana, T. et al., 2019 [121] | SDC | 25 | 42 | |
William, M.D. et al., 2010 [122] | SDC | 66 | 10/66 | 6/10 |
Clauditz, T.S. et al., 2011 [123] | SDC | 14 | 3/14 | 3/3 |
Nardi, V. et al., 2013 [124] | SDC | 27 | - | 29.6 |
Xia, L. et al., 2017 [125] | Invasive carcinoma ex pleomorphic adenoma | 140 | 25 |
Clinical Trial | Study Description | Indication | PEP | Treatment Arms | Outcomes |
---|---|---|---|---|---|
1. Haddad, R. et al., 2003, [109] | Single arm, Phase II, N = 14 | HER2 overexpressing (2+/3+) advanced incurable salivary gland tumors | TP | Trastuzumab |
|
2. Agulnik, M. et al., 2007 [110] | Single arm, Phase II, N = 40 | Progressive, recurrent, or metastatic adenoid cystic carcinoma (ACC) immunohistochemically expressing at least 1+ EGFR and/or 2+ erbB2 | ORR | Lapatinib |
|
3. Takahashi, H. et al., 2019 [113] | Single center, Single arm, Open label, Phase II, N = 57 | Locally advanced and/or recurrent or metastatic HER-positive SDC | ORR | Trastuzumab + Docetaxel |
|
Name of the Study | Number of Patients | Protein Overexpression (%) | Amplification (%) |
---|---|---|---|
Lei, S. et al., 1995 [130] | 27 | 44.4 | - |
Day, J.D. et al., 1996 [131] | 19 | 69 | - |
Dugan, M.C. et al., 1997 [132] | 79 | 58 | - |
Safran, H. et al., 2001 [133] | 154 | 21 | 7.1 |
Novotny, J. et al., 2001 [134] | 57 | 19.2 | - |
Potti et al., 2003 [135] | 39 | None | - |
Hermanova, M. et al., 2004 [136] | 49 | 18.75 | 4 |
Tamiolakis, D. et al., 2004 [137] | 100 | 21 | - |
Sroecklein, N.H. et al., 2004 [138] | 50 | 10 | 24 |
Tsiambas E et al., 2006 [126] | 50 | 59, 22, 12, 8 (0, 1+, 2+ and 3+ expression) | 16 |
Sharif, S. et al., 2008 [139] | 63 | - | 25 |
Komoro, M. et al., 2009 [140] | 129 | 61.2 | - |
Harder, J. et al., 2012 [141] | 207 | 26 | 3.9 |
Chou, A. et al., 2013 [127] | 469 | 7.2 | 2.1 |
Clinical Trial | Study Description | Indication | PEP and Treatment Arms | Outcomes |
---|---|---|---|---|
1. Safran, H. et al., 2004 [128] | Phase II, N = 34 | HER2 overexpressing metastatic pancreatic cancer | OS and Trastuzumab + Gemcitabine vs. Gemcitabine alone |
|
2.Harder, J. et al., 2012 [141] | Multi-center, Phase II, N = 17 | HER2 overexpressing metastatic Pancreatic adenocarcinoma | PFS and Trastuzumab + capecitabine |
|
3. THERAPY TRIAL (NCT00923299) 2015 [129] | Multi-center, Phase I/II, Single arm, Non-randomized | Advanced pancreatic cancer patients after first-line gemcitabine-based chemotherapy failure | ORR, OS, PFS and Trastuzumab + Cetuximab |
|
4. GATE I TRIAL (NCT01204372) 2021 [142] | Multi-center, Phase II, N = 63 | Metastatic pancreatic adenocarcinoma | DCR and Gemcitabine, Trastuzumab, Erlotinib vs. standard therapy |
|
Clinical Trial | Study Description | Indication | PEP | Treatment Arms | Outcomes |
---|---|---|---|---|---|
1. Hussain, M.H.A. et al., 2007 [144] | Multi-center, Phase II, Non-randomized prospective trial, N = 57 | HER2 overexpressing advanced urothelial carcinoma with no prior chemotherapy for metastasis | Cardiac toxicity | Trastuzumab+ Paclitaxel +Carboplatin +Gemcitabine (TPCG) |
|
2. Powles, T. et al., 2016 [145] | Phase III, Double blinded, Randomized, N = 232 | HER1/HER2 expressing metastatic urothelial bladder cancer after first-line chemotherapy for maintenance | PFS | Lapatinib |
|
3. Sheng, X. et al., 2021 [146] | Multi-center, Phase II, Single arm, N = 43 | HER2 expressing (2+/3+) locally advanced or metastatic urothelial carcinoma who previously failed at least one line of systemic chemotherapy. | ORR | RC48-ADC |
|
Clinical Trial | Study Description | Indication | PEP | Treatment Arms | Outcomes |
---|---|---|---|---|---|
1. Ziada, A. et al., 2004 [150] | Single arm, Phase II, N = 18 | HER2 overexpressing advanced hormone refractory prostate cancer | ORR | Trastuzumab |
|
2. Lara, P.N., Jr. et al., 2004 [151] | Open label, Phase II, N = 4 | HER2 overexpressing advanced hormone refractory prostate cancer | OS | Trastuzumab or Docetaxel alone followed by Trastuzumab + Docetaxel |
|
3. Curigliano, G. et al., 2007 [152] | Phase II, N = 23 | Hormone-refractory prostate cancer. | PSA measurement | Gefitinib + antiandrogen + Luteinizing releasing hormone analogue |
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4. De Bono, J.S. et al., 2007 [153] | Open label, Phase II, N = 23 | Castrate patient with hormone refractory prostate cancer | Prostate-specific antigen (PSA) 50% decline rate within 24 weeks | Pertuzumab at 420 mg vs. 1050 mg |
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5. Agus, D.B. et al., 2007 [154] | Phase II, N = 42 | Castration-resistant prostate cancer (CRPC) patients who had experienced progression after at least one taxane-based regimen. | Safety, ORR | Single agent Pertuzumab |
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6. Vuky, J. et al., 2009 [155] | Phase II, N = 31 | Neoadjuvant therapy in high-risk localized prostate cancer before radical prostatectomy | PCR | Gefitinib + Docetaxel |
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7. Whang, Y.E. et al., 2013 [156] | Multi-center, Phase II, Open label, N = 29 | Rising PSA levels on androgen deprivation therapy and chemotherapy naïve prostate cancer | >50% confirmed PSA decline from baseline | Lapatinib |
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Amisha, F.; Malik, P.; Saluja, P.; Gautam, N.; Patel, T.H.; Roy, A.M.; Singh, S.R.K.; Malapati, S.J. A Comprehensive Review on the Role of Human Epidermal Growth Factor Receptor 2 (HER2) as a Biomarker in Extra-Mammary and Extra-Gastric Cancers. Onco 2023, 3, 96-124. https://doi.org/10.3390/onco3020008
Amisha F, Malik P, Saluja P, Gautam N, Patel TH, Roy AM, Singh SRK, Malapati SJ. A Comprehensive Review on the Role of Human Epidermal Growth Factor Receptor 2 (HER2) as a Biomarker in Extra-Mammary and Extra-Gastric Cancers. Onco. 2023; 3(2):96-124. https://doi.org/10.3390/onco3020008
Chicago/Turabian StyleAmisha, Fnu, Paras Malik, Prachi Saluja, Nitesh Gautam, Tanvi Harishbhai Patel, Arya Mariam Roy, Sunny R. K. Singh, and Sindhu Janarthanam Malapati. 2023. "A Comprehensive Review on the Role of Human Epidermal Growth Factor Receptor 2 (HER2) as a Biomarker in Extra-Mammary and Extra-Gastric Cancers" Onco 3, no. 2: 96-124. https://doi.org/10.3390/onco3020008