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Role of HER2 in Gastric Cancers

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Gastric Cancer

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Abstract

The majority of patients with gastric cancer present with advanced disease, which is incurable. Molecularly targeted therapies, such as those targeting human epidermal growth factor receptor 2 (HER2), are anticipated to improve the current status of systemic treatment beyond conventional cytotoxic therapy. Trastuzumab in combination with chemotherapy in patients is the first molecular agent in metastatic HER2-positive gastric and gastroesophageal to result in improvements in response rates, time to progression and survival. Trastuzumab is now being investigated in the neoadjuvant and adjuvant setting. Unfortunately, as with breast cancer, many esophagogastric patients will develop resistance to trastuzumab. Several promising therapeutic agents are currently under investigation as monotherapy and in combination with chemotherapy in the first and second line setting. New avenues of research into mechanisms of resistance and technology to better diagnose and treat HER2 gastric cancer are being actively studied.

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References

  1. Ferlay J, Shin H-R, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917. doi: 10.1002/ijc.25516.

    Article  CAS  PubMed  Google Scholar 

  2. Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 1996;335:462–7.

    Article  Google Scholar 

  3. Bang YJ, Van Custem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for the treatment of HER2-positive advanced gastric or gastro-oesophageal cancer (ToGA): a phase 3, open-label, randomized controlled trial. Lancet. 2010;376:687–97.

    Article  CAS  PubMed  Google Scholar 

  4. Yarden Y. The EGFR family and its ligands in human cancer, signaling mechanisms and therapeutic opportunities. Eur J Cancer. 2001;37 (Suppl 4):S3–S8.

    Article  CAS  PubMed  Google Scholar 

  5. Bang Y, Chung H, Xu J, et al. Pathological features of advanced gastric cancer (GC): relationship to human epidermal growth factor receptor 2 (HER2) positivity in the global screening programme of the ToGA trial. J Clin Oncol. 2009;27:15 (supp; abst 4556).

    Article  Google Scholar 

  6. Tanner M, Hollmén M, Junttila TT, et al. Amplification of HER-2 in gastric carcinoma: association with topoisomerase IIα gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol. 2005;16:273–8.

    Article  CAS  PubMed  Google Scholar 

  7. Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52:797–805.

    Article  CAS  PubMed  Google Scholar 

  8. Rüschoff J, Dietel M, Baretton G, et al. HER2 diagnostics in gastric cancer—guideline validation and development of standardized immunohistochemical testing. Virchows Archiv. 2010;457:299–307.

    Article  PubMed Central  PubMed  Google Scholar 

  9. National Comprehensive Cancer Network (NCCN). Esophageal and esophagogastric junction cancers. Version 2.2013. http://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf. Accessed 11 March 2014.

  10. Ruschoff J, Hanna W, Bilous M, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol 2012:25:637–50.

    Article  PubMed  Google Scholar 

  11. Nakajim M, Sawad H, Yamada Y, et al. The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer. 1999;85:1894–902.

    Article  Google Scholar 

  12. Park DI, Yun JW, Park JH, et al. HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci. 2006;51:1371–79.

    Article  CAS  PubMed  Google Scholar 

  13. Terashima M, Ochiai A, Kitada K, et al. Impact of human epidermal growth factor (EGFR) and ERBB2 (HER2) expressions on survival in patients with stage II/III gastric cancer, enrolled in the ACTS-GC study. J Clin Oncol. 2011;29 (suppl; abstr 4013).

    Google Scholar 

  14. Yoon HH, Shi Q, Sukov WR, et al. HER2 expression/amplification: frequency, clinicopathologic features, and prognosis in 713 patients with esophageal adenocarcinoma (EAC). J Clin Oncol. 2011;29 (Suppl). (Abstr 4012).

    Google Scholar 

  15. Grabsch H, Sivakumar S, Gray S, et al. HER2 expression in gastric cancer: rare, heterogeneous and of no prognostic value—conclusions from 924 cases of two independent series. Cell Oncol. 2010;32:57–65.

    PubMed  Google Scholar 

  16. Janjigian YY, Werner D, Pauligk C, et al. Prognostic significance of human epidermal growth factor-2 (HER2) in advanced gastric cancer: a US and European international collaborative analysis. Ann Oncol. 2012;23(10):2656–62.

    Article  CAS  PubMed  Google Scholar 

  17. Ajani JA, Rodriguez W, Bodoky G, et al. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusion fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol 2010;28:1547–53.

    Article  CAS  PubMed  Google Scholar 

  18. Vanhoefer U, Rougier P, Wilke H, et al. Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol. 2000;18:2648–57.

    CAS  PubMed  Google Scholar 

  19. Lordick F, Kang YK, Chung HC, et al. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomized, open-label phase 3 trial. Lancet Oncol. 2013;14:490–9.

    Article  CAS  PubMed  Google Scholar 

  20. Hudziak RM, Lewis GD, Winget M, et al. p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor. Mol Cell Biol. 1989;9:1165–72.

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Baselga J, Tripathy D, Mendelsohn J, et al. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol. 1996;14:737–44.

    CAS  PubMed  Google Scholar 

  22. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92.

    Article  CAS  PubMed  Google Scholar 

  23. Guiu S, Gauthier M, Coudert B, et al. Pathological complete response and survival according to the level of HER-2 amplification after trastuzumab based neoadjuvant therapy for breast cancer. Br J Cancer. 2010;103:1335–42.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Gomez-Martin C, Plaza JC, Pazo-Cid R, et al. Level of HER2 gene amplification predicts response to overall survival in HER2-positive advanced gastric cancer treated with trastuzumab. J Clin Oncol. 2013;31:4445–52.

    Article  CAS  PubMed  Google Scholar 

  25. Bruno R, Washington CB, Lu JF, et al. Population pharmacokinetics of trastuzumab in patients with HER2 + metastatic breast cancer. Cancer Chemother Pharmacol. 2005;56:361–9.

    Article  CAS  PubMed  Google Scholar 

  26. Roche, Inc. Herceptin package insert. http://www.medsafe.govt.nz/profs/datasheet/h/Herceptininf.pdf. Accessed 3 April 2014.

  27. Hoffmann-La Roche. HELOISE study: a study of Herceptin (trastuzumab) in combination with chemotherapy in patients with HER2-positive metastatic gastric or gastro-esophageal cancer. In: ClinicalTrials.gov. Bethesda, MD: National Library of Medicine (US). http://clinicaltrials.gov/show/NCT01450696. NLM Identifier: NCT01450696. Accessed 3 April 2014.

  28. Hoffmann-La Roche. A study of capecitabine (Xeloda) in combination with trastuzumab (Herceptin) and oxaliplatin in patients with resectable gastric cancer. In: ClinicalTrials.gov. Bethesda, MD: National Library of Medicine (US). http://clinicaltrials.gov/show/NCT01130337. NLM Identifier: NCT01130337. Accessed 18 March 2014.

  29. National Cancer Institute (NCI.) Radiation therapy, paclitaxel, and carboplatin with or without trastuzumab in treating patients with esophageal cancer (RTOG 1010 Trial) In: ClinicalTrials.gov. Bethesda, MD: National Library of Medicine (US). http://clinicaltrials.gov/show/NCT01196390. NLM Identifier: NCT01196390. Accessed 18 March 2014.

  30. Hoffmann-La Roche. A study of the combination of oxaliplatin, capecitabine and Herceptin (trastuzumab) and chemoradiotherapy in the adjuvant setting in operated patients with HER2 + gastric or gastroesophageal junction cancer (TOXAG Study). In: ClinicalTrials.gov. Bethesda, MD: National Library of Medicine (US). Available from: http://clinicaltrials.gov/show/NCT01748773. NLM Identifier: NCT01748773. Accessed 18 March 2014.

  31. Gajria D, Chandarlapaty S. Her2-amplified breast cancer: mechanisms of resistance and novel targeted therapies. Expert Rev Anticancer Ther. 2011;11:263–75.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Berns K, Horlings HM, Hennessy BT, et al. A functional genetic approach identifies the P13K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell. 2007;12:395–402.

    Article  CAS  PubMed  Google Scholar 

  33. Nahta R, Yuan LXH, Zhang B, et al. Insulin-like growth factor-1 receptor/human epidermal growth factor receptor2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res. 2005;65:11118–28.

    Article  CAS  PubMed  Google Scholar 

  34. Ritter CA, Perez-Torres M, Rinehart C, et al. Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network. Clin Cancer Res. 2007;13:4909–19.

    Article  CAS  PubMed  Google Scholar 

  35. Muller WJ, Arteaga CL, Muthuswamy SK, et al. Synergistic interaction of the Neu proto-oncogene product and transforming growth factor alpha in the mammary epithelium of transgenic mice. Mol Cell Biol. 1996;16:5726–36.

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Lenferink AE, Simpson JF, Shawver LK, et al. Blockade of the epidermal growth factor receptor tyrosine kinase suppresses tumorigenesis in MMTV/Neu + MMTV/TGF-alpha bigenic mice. Proc Natl Acad Sci U S A. 2000;97:9609–14.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. DiGiovanna MP, Stern DF, Edgerton SM, et al. Relationship of epidermal growth factor receptor expression to ErbB-2 signaling activity and prognosis in breast cancer patients. J Clin Oncol. 2005;23:1152–60.

    Article  CAS  PubMed  Google Scholar 

  38. Kim YJ, Kim MA, Im SA, et al. Metastasis-associated protein S100A4 and p53 predict relapse in curatively resected stage III and IV (M0) gastric cancer. Cancer Invest. 2008;26:152–8.

    Article  CAS  PubMed  Google Scholar 

  39. Galizia G, Lieto E, Orditura M, et al. Prognostic biomarkers and targeted therapy in gastric cancer: reply. World J Surg. 2008;32:1227–9.

    Article  Google Scholar 

  40. Baselga J, Cortes J, Kim S-B, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. New Engl J Med. 2012;366:109–19.

    Article  CAS  PubMed  Google Scholar 

  41. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory early HER2-positive breast cancer (NeoSphere): a randomized multicentre, open-label, phase 2 trial.

    Google Scholar 

  42. Yamashita-Kashima Y, Iijima S, Yoruzu K, et al. Pertuzumab in combination with trastuzumab shows significantly enhanced antitumor activity in HER2-positive human gastric cancer xenograft models. Clin Cancer Res. 2011;15:5060–70.

    Article  Google Scholar 

  43. Tabernero J, Marcelo Hoff P, Shen L, et al. Pertuzumab (P) with trastuzumab (T) and chemotherapy (CTX) in HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer: an international phase III study (JACOB). J Clin Oncol. 2013; (suppl TPS4150).

    Google Scholar 

  44. Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Eng J Med. 2012;367:1783–91.

    Article  CAS  Google Scholar 

  45. Barok M, Tanner M, Koninki K, et al. Trastuzumab-DM1 is highly effective in preclinical models of HER2-positive gastric cancer. Cancer Lett. 2011;306:171–9.

    Article  CAS  PubMed  Google Scholar 

  46. Yamashita-Kashima Y, Shu S, Harada N, et al. Potentiation of trastuzumab emtansine (T-DM1)-driven antitumor activity by pertuzumab in a HER2-positive gastric cancer model. J Clin Oncol. 2012; (suppl; abstr e13502).

    Google Scholar 

  47. Hoffmann-La Roche. A study of trastuzumab emtansine versus taxane in patients with advanced gastric cancer. In: ClinicalTrials.gov. Bethesda, MD: National Library of Medicine (US). Available from: http://clinicaltrials.gov/show/NCT01641939. NLM Identifier: NCT01641939. Accessed 18 March 2014.

  48. Gomez HL, Doval DC, Chavez MA, et al. Efficacy and safety of lapatinib as first-line therapy for ErbB2-amplified locally advanced or metastatic breast cancer. J Clin Oncol. 2008;26:2999–3005.

    Article  CAS  PubMed  Google Scholar 

  49. Blackwell KL, Burstein HJ, Storniolo AM, et al. Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010;28:1124–30.

    Article  CAS  PubMed  Google Scholar 

  50. Iqbal S, Goldman B, Fenoglio-Preiser CM, et al. Southwest oncology group study S0413: a phase II trial of lapatinib (GW572016) as first-line therapy in patients with advanced or metastatic gastric cancer. Ann Oncol. 2011;22:2610–15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Hecht JR, Bang Y-J, Qin S, et al. Lapatinib in combination with capecitabine plus oxaliplatin (CapeOx) in HER2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma (AC): the TRIO-013/LOGiC Trial. J Clin Oncol. 2013;31 (suppl; abstr LBA4001). Presented June 3, 2013 at 2013 ASCO Annual Meeting, Chicago, IL.

    Google Scholar 

  52. Bang YJ. A randomized, open-label, phase III study of lapatinib in combination with paclitaxel versus weekly paclitaxel alone in the second-line treatment of HER2 amplified advanced gastric cancer (AGC) in Asian population: Tytan study. J Clin Oncol. 2012;30 (suppl 34; abstr 11).

    Google Scholar 

  53. Burstein HJ, Sun Y, Dirix LY, et al. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer. J Clin Oncol. 2010;28:1301–7.

    Article  CAS  PubMed  Google Scholar 

  54. Park JW, Liu MC, Yee D, et al. Neratinib plus standard neoadjuvant therapy for high-risk breast cancer: efficacy results from the I-SPY 2 TRIAL. American Association for Cancer Research (AACR) Annual Meeting, San Diego, presented April 7, 2014, Abstract CT 227.

    Google Scholar 

  55. Puma Biotechnology Inc. A study of neratinib plus capecitabine versus lapatinib plus capecitabine in patients with HER2 + Metastatic Breast Cancer Who Have Received Two or More Prior HER2 Directed Regimens in the Metastatic Setting (NALA). In: ClinicalTrials.gov. Bethesda, MD: National Library of Medicine (US). http://clinicaltrials.gov/show/NCT01808573. NLM Identifier: NCT01808573. Accessed 18 May 2014.

  56. Puma Biotechnology Inc. An open-label, phase 2 study of neratinib in patients with solid tumors with somatic human epidermal growth factor receptor (EGFR, HER2, HER3) mutations or EGFR gene amplification. In: ClinicalTrials.gov. Bethesda, MD: National Library of Medicine (US). http://clinicaltrials.gov/show/NCT 01953926. NLM Identifier: NCT 01953926. Accessed 18 May 2014.

  57. Janjigian YY, Viola-Villega N, Holland JP, et al. Monitoring afatinib treatment in HER2-positive gastric cancer with 18F-FDG and 89 Zr-Trastuzumab PET. J Nucl Med. 2013;54:936–43.

    Article  CAS  PubMed  Google Scholar 

  58. Memorial Sloan Kettering Cancer Center. Afatinib (BIBW2992) in patients with advanced HER2-positive trastuzumab-refractory advanced esophagogastric cancer. In: ClinicalTrials.gov. Bethesda, MD: National Library of Medicine (US). http://clinicaltrials.gov/show/NCT 01522768. NLM Identifier: NCT 01522768. Accessed 18 May 2014.

  59. Janjigian YY, Capanu M, Imtiaz T, et al. A phase II study of afatinib in patients (pts) with metastatic human epidermal growth factor receptor (HER2)-positive trastuzumab-refractory esophagogastric (EG) cancer. J Clin Oncol. 2014; (supp l3; abstr 52).

    Google Scholar 

  60. Guarneri V, Giovannelli S, Ficarra G, et al. Comparison of HER-2 and hormone receptor expression in primary breast cancers and asynchronous paired metastases: impact on patient management. Oncologist. 2008;13:838–44.

    Article  CAS  PubMed  Google Scholar 

  61. Solomayer EF, Becker S, Pergola-Becker G, et al. Comparison of HER2 status between primary tumor and disseminated tumor cells in primary breast cancer patients. Breast Cancer Res. Treat. 2006;98:179–84.

    Article  CAS  PubMed  Google Scholar 

  62. Zurrida S, Montagna E, Naninato P, et al. Receptor status (ER, PgR and HER2) discordance between primary tumor and locoregional recurrence in breast cancer. Ann Oncol. 2011;22:479–80.

    Article  CAS  PubMed  Google Scholar 

  63. Sekido Y, Umemura S, Takekoshi S, et al. Heterogeneous gene alterations in primary breast cancer contribute to discordance between primary and asynchronous metastatic/recurrent sites: HER2 gene amplification and p53 mutation. Int J Oncol. 2003;22:1225–32.

    CAS  PubMed  Google Scholar 

  64. Leyland-Jones B, Colomer R, Trudeau ME, et al. Intensive loading dose of trastuzumab achieves higher-than-steady-state serum concentrations and is well tolerated. J Clin Oncol. 2010;28:960–6.

    Article  CAS  PubMed  Google Scholar 

  65. Oude Munnink TH, Dijkers EC, Netters SJ, et al. Trastuzumab pharmacokinetics influenced by extent human epidermal growth factor receptor 2-positive tumor load. J Clin Oncol. 2010;28:e355–6 (author reply).

    Article  PubMed  Google Scholar 

  66. Dijkers EC, Oude Munnink TH, KOsterink JG, et al. Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther. 2010;87:586–92.

    Article  CAS  PubMed  Google Scholar 

  67. Memorial Sloan Kettering Cancer Center. PET imaging with 89Zr-DFO-Trastuzumab in esophagogastric cancer. In: ClinicalTrials.gov. Bethesda, MD: National Library of Medicine (US). http://clinicaltrials.gov/show/NCT 02023996. NLM Identifier: NCT 02023996. Accessed 18 May 2014.

  68. Sausville EA, Burger AM. Contributions of human tumor xenografts to anticancer drug development. Cancer Res. 2006;66:3351–4 (discussion 4).

    Article  CAS  PubMed  Google Scholar 

  69. Daniel VC, Marchionni L, Hierman JS, et al. A primary xenograft model of small-cell lung cancer reveals irreversible changes in gene expression imposed by culture in vitro. Cancer Res. 2009;69:3364–73.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Siolas D, Hannon GJ. Patient derived tumor xenografts: transforming clinical samples into mouse models. Cancer Res. 2013;73:5315–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Dangles-Marie V, Pocard M, Richon S, et al. Establishment of human colon cancer cell lines from fresh tumors versus xenografts: comparison of success rate and cell line features. Cancer Res. 2007;67:398–407.

    Article  CAS  PubMed  Google Scholar 

  72. Janjigian YY, Vakiani E, Imtiaz T, et al. Patient derived xenografts (PDX) as models for the identification of predictive biomarkers in esophagogastric (EG) cancer. J Clin Oncol Proc ASCO 2014 (abstract 4059).

    Google Scholar 

  73. Dulak AM, Stojanov P, Peng S, et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet. 2013;45:478–86.

    Article  CAS  PubMed  Google Scholar 

  74. Wang K, Yuen ST, Xu J, et al. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet. 2014 May 11 [Epub ahead of print].

    Google Scholar 

  75. Kakiuchi M, Nishizawa T, Ueda H, et al. Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma. Nat Genet. 2014 May 11 [Epub ahead of print].

    Google Scholar 

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Authors and Affiliations

  1. Gastrointestinal Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Elizabeth Won MD

  2. Gastrointestinal Oncology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, 300 E66th Street, Room 1033, New York, NY, 10065, USA

    Yelena Y. Janjigian MD

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  1. Elizabeth Won MD
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Correspondence to Yelena Y. Janjigian MD .

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  1. Gastric and Mixed Tumor Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Vivian E. Strong

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Won, E., Janjigian, Y. (2015). Role of HER2 in Gastric Cancers. In: Strong, V. (eds) Gastric Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-15826-6_5

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