erbb 2 genes


Summary: The erbB-2 gene is a proto-oncogene that codes for the erbB-2 receptor (RECEPTOR, ERBB-2), a protein with structural features similar to the epidermal growth factor receptor. Its name originates from the viral oncogene homolog (v-erbB) which is a truncated form of the chicken erbB gene found in the avian erythroblastosis virus. Overexpression and amplification of the gene is associated with a significant number of adenocarcinomas. The human c-erbB-2 gene is located at 17q21.2.

Top Publications

  1. Gullo G, Bettio D, Torri V, Masci G, Salvini P, Santoro A. Level of HER2/neu gene amplification as a predictive factor of response to trastuzumab-based therapy in patients with HER2-positive metastatic breast cancer. Invest New Drugs. 2009;27:179-83 pubmed publisher
    ..If confirmed in larger cohorts of patients, HER2/CEP17 ratio could represent a reliable and economical predictor of response to trastuzumab-based therapy in MBC. ..
  2. Dietel M, Ellis I, Hofler H, Kreipe H, Moch H, Dankof A, et al. Comparison of automated silver enhanced in situ hybridisation (SISH) and fluorescence ISH (FISH) for the validation of HER2 gene status in breast carcinoma according to the guidelines of the American Society of Clinical Oncology and the College of Am. Virchows Arch. 2007;451:19-25 pubmed
    ..Because SISH combines bright field microscopy with molecular analysis and full automation, it appears to be particularly suited for routine application in surgical pathology. ..
  3. Bartlett J, Campbell F, Mallon E. Determination of HER2 amplification by in situ hybridization: when should chromosome 17 also be determined?. Am J Clin Pathol. 2008;130:920-6 pubmed publisher
    ..We recommend that all breast cancer cases with a HER2 copy number of 2 to 7 determined by single-color in situ hybridization should also be analyzed for chromosome 17 to obtain a more accurate diagnosis of HER2 amplification. ..
  4. Zaczek A, Wełnicka Jaśkiewicz M, Bielawski K, Jaskiewicz J, Badzio A, Olszewski W, et al. Gene copy numbers of HER family in breast cancer. J Cancer Res Clin Oncol. 2008;134:271-9 pubmed
    ..The aim of the study was to analyze the occurrence of abnormal gene copy numbers of all HER oncogenes and to correlate these alterations to other clinicopathological variables in a consecutive series of 225 breast cancer patients...
  5. Hyun C, Lee H, Kim K, Kim S, Kim J, Choe G, et al. The effect of chromosome 17 polysomy on HER-2/neu status in breast cancer. J Clin Pathol. 2008;61:317-21 pubmed
    ..However, cases in which CISH indicates the presence of borderline copy numbers or low levels of amplification may need FISH to rule out polysomy 17 and to determine HER-2 gene amplification status accurately. ..
  6. Cao Y, Luo J, Karin M. IkappaB kinase alpha kinase activity is required for self-renewal of ErbB2/Her2-transformed mammary tumor-initiating cells. Proc Natl Acad Sci U S A. 2007;104:15852-7 pubmed
    ..IKKalpha may represent a novel and specific target for treatment of ErbB2-positive breast cancer. ..
  7. Chivukula M, Bhargava R, Brufsky A, Surti U, Dabbs D. Clinical importance of HER2 immunohistologic heterogeneous expression in core-needle biopsies vs resection specimens for equivocal (immunohistochemical score 2+) cases. Mod Pathol. 2008;21:363-8 pubmed publisher
    ..However, performing fluorescence in situ hybridization on core-needle biopsies almost completely resolves the issue of heterogeneous expression of HER2. ..
  8. Cottu P, Asselah J, Lae M, Pierga J, Dieras V, Mignot L, et al. Intratumoral heterogeneity of HER2/neu expression and its consequences for the management of advanced breast cancer. Ann Oncol. 2008;19:595-7 pubmed publisher
  9. Faratian D, Goltsov A, Lebedeva G, Sorokin A, Moodie S, Mullen P, et al. Systems biology reveals new strategies for personalizing cancer medicine and confirms the role of PTEN in resistance to trastuzumab. Cancer Res. 2009;69:6713-20 pubmed publisher

More Information


  1. Kim M, Jung E, Lee H, Lee H, Jeon Y, Yang H, et al. Evaluation of HER-2 gene status in gastric carcinoma using immunohistochemistry, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction. Hum Pathol. 2007;38:1386-93 pubmed
    ..9% specificity using FISH results as the standard. Measurements of HER-2 expression by FISH and real-time q-PCR and of HER-2 protein by IHC were found to be highly concordant at determining HER-2 status in gastric carcinoma. ..
  2. Sińczak Kuta A, Tomaszewska R, Rudnicka Sosin L, Okon K, Stachura J. Evaluation of HER2/neu gene amplification in patients with invasive breast carcinoma. Comparison of in situ hybridization methods. Pol J Pathol. 2007;58:41-50 pubmed
  3. Sassen A, Rochon J, Wild P, Hartmann A, Hofstaedter F, Schwarz S, et al. Cytogenetic analysis of HER1/EGFR, HER2, HER3 and HER4 in 278 breast cancer patients. Breast Cancer Res. 2008;10:R2 pubmed publisher
    ..However, the clinical outcome with regard to total HER receptor state remains largely unknown...
  4. Grushko T, Filiaci V, Mundt A, Ridderstråle K, Olopade O, Fleming G. An exploratory analysis of HER-2 amplification and overexpression in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2008;108:3-9 pubmed
    ..There was no clear evidence for a survival difference or a difference in benefit from the addition of paclitaxel for women with HER-2 amplified or overexpressed tumors; however, power to detect clinically meaningful differences was low. ..
  5. Piechocki M, Yoo G, Dibbley S, Lonardo F. Breast cancer expressing the activated HER2/neu is sensitive to gefitinib in vitro and in vivo and acquires resistance through a novel point mutation in the HER2/neu. Cancer Res. 2007;67:6825-43 pubmed
    ..This model will be useful in understanding the differences between intrinsic drug sensitivity and acquired resistance in the context of therapeutic strategies that target oncogene addicted diseases. ..
  6. Pritchard K, Messersmith H, Elavathil L, Trudeau M, O Malley F, Dhesy Thind B. HER-2 and topoisomerase II as predictors of response to chemotherapy. J Clin Oncol. 2008;26:736-44 pubmed publisher
    ..Additional studies will be required to clarify these relationships. ..
  7. Moasser M. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene. 2007;26:6469-87 pubmed
    ..Here I review the evidence supporting the oncogenic function of HER2, the mechanisms that are felt to mediate its oncogenic functions, and the evidence that links the experimental evidence with human cancer pathogenesis. ..
  8. Bartlett J, Campbell F, Ibrahim M, Wencyk P, Ellis I, Kay E, et al. Chromogenic in situ hybridization: a multicenter study comparing silver in situ hybridization with FISH. Am J Clin Pathol. 2009;132:514-20 pubmed publisher
    ..The Ventana INFORM HER-2 SISH assay is robust and reproducible, shows good concordance with a standard FISH assay, and complies with requirements in national guidelines for performance of diagnostic tests. ..
  9. Rauser S, Weis R, Braselmann H, Feith M, Stein H, Langer R, et al. Significance of HER2 low-level copy gain in Barrett's cancer: implications for fluorescence in situ hybridization testing in tissues. Clin Cancer Res. 2007;13:5115-23 pubmed
    ..These results should be taken into account for accurate evaluation of biomarkers by FISH and for HER2 FISH testing in tissue sections. ..
  10. Paik S, Kim C, Wolmark N. HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med. 2008;358:1409-11 pubmed publisher
  11. Sauter G, Lee J, Bartlett J, Slamon D, Press M. Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J Clin Oncol. 2009;27:1323-33 pubmed publisher
    ..Until other methods achieve similar test accuracy, reproducibility, and predictive value, we suggest FISH as the primary HER-2 testing modality for women with breast cancer who are candidates for HER-2-targeted therapies. ..
  12. Tuefferd M, Couturier J, Penault Llorca F, Vincent Salomon A, Broet P, Guastalla J, et al. HER2 status in ovarian carcinomas: a multicenter GINECO study of 320 patients. PLoS ONE. 2007;2:e1138 pubmed
    ..This raises the question of whether HER2 status and paclitaxel sensitively are linked. ..
  13. Dowsett M, Procter M, McCaskill Stevens W, de Azambuja E, Dafni U, Rueschoff J, et al. Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial. J Clin Oncol. 2009;27:2962-9 pubmed publisher
    ..There was no evidence for reduced benefit of trastuzumab in HER2 IHC2+FISH+ cases. The degree of HER2 amplification does not influence prognosis or benefit from adjuvant trastuzumab in patients treated with prior adjuvant chemotherapy. ..
  14. Gown A, Goldstein L, Barry T, Kussick S, Kandalaft P, Kim P, et al. High concordance between immunohistochemistry and fluorescence in situ hybridization testing for HER2 status in breast cancer requires a normalized IHC scoring system. Mod Pathol. 2008;21:1271-7 pubmed publisher
  15. Hansel D, Swain E, Dreicer R, Tubbs R. HER2 overexpression and amplification in urothelial carcinoma of the bladder is associated with MYC coamplification in a subset of cases. Am J Clin Pathol. 2008;130:274-81 pubmed publisher
    ..Further studies into the role of MYC coamplification in this population are needed to determine impacts on treatment with HER2-targeted therapy. ..
  16. Hicks D, Kulkarni S. HER2+ breast cancer: review of biologic relevance and optimal use of diagnostic tools. Am J Clin Pathol. 2008;129:263-73 pubmed publisher
    ..Rigorous quality control and standardization of the testing process, from the handling of tissue samples to interpretation and reporting of results, are essential for achieving accurate and reproducible assay results. ..
  17. Yuan T, Cantley L. PI3K pathway alterations in cancer: variations on a theme. Oncogene. 2008;27:5497-510 pubmed publisher
    ..In this review, we will examine the oncogenic properties of these genetic alterations to understand whether they are redundant or distinct and propose treatment strategies tailored for these genetic lesions. ..
  18. Moasser M. Targeting the function of the HER2 oncogene in human cancer therapeutics. Oncogene. 2007;26:6577-92 pubmed
    ..Here, I review the development of treatments that target HER2 in the context of the HER2 oncogene hypothesis, and where we stand with regards to the clinical translation of the HER2 oncogene hypothesis. ..
  19. Ross J. Breast cancer biomarkers and HER2 testing after 10 years of anti-HER2 therapy. Drug News Perspect. 2009;22:93-106 pubmed publisher
    ..Also of significant interest are the evolving lists of biomarkers proposed to predict resistance to the major anti-HER2 therapies, trastuzumab and lapatinib. ..
  20. Wolff A, Hammond M, Schwartz J, Hagerty K, Allred D, Cote R, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007;131:18-43 pubmed publisher
    ..The panel recommends that HER2 testing be done in a CAP-accredited laboratory or in a laboratory that meets the accreditation and proficiency testing requirements set out by this document. ..
  21. Marchio C, Natrajan R, Shiu K, Lambros M, Rodriguez Pinilla S, Tan D, et al. The genomic profile of HER2-amplified breast cancers: the influence of ER status. J Pathol. 2008;216:399-407 pubmed publisher
    ..In conclusion, although hormone receptor status does not determine the overall genetic profile of HER2-amplified breast cancers, specific genetic aberrations may be characteristic of subgroups of HER2 breast cancers. ..
  22. Dean Colomb W, Esteva F. Her2-positive breast cancer: herceptin and beyond. Eur J Cancer. 2008;44:2806-12 pubmed publisher
  23. Gong Y, Sweet W, Duh Y, Greenfield L, Fang Y, Zhao J, et al. Chromogenic in situ hybridization is a reliable method for detecting HER2 gene status in breast cancer: a multicenter study using conventional scoring criteria and the new ASCO/CAP recommendations. Am J Clin Pathol. 2009;131:490-7 pubmed publisher
    ..0% among 3 sites using the manufacturers' criteria and 100.0% between 2 sites using the ASCO/CAP criteria. Our results confirm that CISH is reliable for HER2 testing per ASCO/CAP guidelines. ..
  24. Kim S, Kim H, Kim Y, Oh D, Im S, Lee D, et al. Trastuzumab inhibits the growth of human gastric cancer cell lines with HER2 amplification synergistically with cisplatin. Int J Oncol. 2008;32:89-95 pubmed
    ..These results suggest that trastuzumab combined with chemotherapeutic agents can be active against gastric cancer with HER2 amplification. ..
  25. Jensen K, Turbin D, Leung S, Miller M, Johnson K, Norris B, et al. New cutpoints to identify increased HER2 copy number: analysis of a large, population-based cohort with long-term follow-up. Breast Cancer Res Treat. 2008;112:453-9 pubmed publisher
    ..2. These findings suggest that a new cut point to determine HER2 positivity, at a ratio of 1.5 (well below the current recommended cut point of 2.2), should be evaluated. ..
  26. Pedersen M, Rasmussen B. The correlation between dual-color chromogenic in situ hybridization and fluorescence in situ hybridization in assessing HER2 gene amplification in breast cancer. Diagn Mol Pathol. 2009;18:96-102 pubmed publisher
    ..In conclusion, it is possible by dual-color CISH method to demonstrate HER2 genes and chromosome 17 genes, in the same tissue section and reliably assess HER2 status. The CISH method is a very promising alternative to the FISH method. ..
  27. Di Palma S, Collins N, Bilous M, Sapino A, Mottolese M, Kapranos N, et al. A quality assurance exercise to evaluate the accuracy and reproducibility of chromogenic in situ hybridisation for HER2 analysis in breast cancer. J Clin Pathol. 2008;61:757-60 pubmed publisher
    ..The results show that CISH is a robust technique providing a suitable assay for the frontline testing of HER2 status in breast cancer. ..
  28. Pestrin M, Bessi S, Galardi F, Truglia M, Biggeri A, Biagioni C, et al. Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients. Breast Cancer Res Treat. 2009;118:523-30 pubmed publisher
    ..278). Our study suggests that a subset of patients with HER2-negative primary tumors develops HER2-positive CTCs during disease progression. ..
  29. Scaltriti M, Rojo F, Ocana A, Anido J, Guzman M, Cortes J, et al. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst. 2007;99:628-38 pubmed
    ..029). Breast tumors that express p95HER2 are resistant to trastuzumab and may require alternative or additional anti-HER2-targeting strategies. ..
  30. Piccart Gebhart M. Adjuvant trastuzumab therapy for HER2-overexpressing breast cancer: what we know and what we still need to learn. Eur J Cancer. 2006;42:1715-9 pubmed
  31. Barrett C, Magee H, O Toole D, Daly S, Jeffers M. Amplification of the HER2 gene in breast cancers testing 2+ weak positive by HercepTest immunohistochemistry: false-positive or false-negative immunohistochemistry?. J Clin Pathol. 2007;60:690-3 pubmed
    ..This has implications for selection of cases for FISH analysis where weak positive (2+) IHC score is used as a triage for FISH testing, and for testing strategies in referral laboratories undertaking FISH analysis. ..
  32. Shipley J. Putting the colours into chromogenic in situ hybridization (CISH). J Pathol. 2006;210:1-2 pubmed
  33. Bouchalova K, Trojanec R, Kolar Z, Cwiertka K, Cernakova I, Mihal V, et al. Analysis of ERBB2 and TOP2A gene status using fluorescence in situ hybridization versus immunohistochemistry in localized breast cancer. Neoplasma. 2006;53:393-401 pubmed
    ..However, our study points to the importance of FISH examination of TOP2A gene status in all tumors with ERBB2 amplification. ..
  34. Di Palma S, Collins N, Faulkes C, Ping B, Ferns G, Haagsma B, et al. Chromogenic in situ hybridisation (CISH) should be an accepted method in the routine diagnostic evaluation of HER2 status in breast cancer. J Clin Pathol. 2007;60:1067-8 pubmed
  35. Steffensen K, Waldstrøm M, Jeppesen U, Jakobsen E, Brandslund I, Jakobsen A. The prognostic importance of cyclooxygenase 2 and HER2 expression in epithelial ovarian cancer. Int J Gynecol Cancer. 2007;17:798-807 pubmed
    ..Positive HER2 expression also notified a grave prognosis, but the low rate of overexpression reduces its potential clinical application. ..
  36. Laakso M, Tanner M, Isola J. Dual-colour chromogenic in situ hybridization for testing of HER-2 oncogene amplification in archival breast tumours. J Pathol. 2006;210:3-9 pubmed
    ..It is concluded that dual-colour CISH, which is a new alternative to FISH enables the assessment of copy number ratio (HER-2/17 centromere) in conjunction with proper histopathological evaluation and the ease of bright-field microscopy. ..
  37. Tapia C, Glatz K, Novotny H, Lugli A, Horcic M, Seemayer C, et al. Close association between HER-2 amplification and overexpression in human tumors of non-breast origin. Mod Pathol. 2007;20:192-8 pubmed
    ..Such tumor entities should be carefully evaluated for a possible utility of trastuzumab treatment. ..
  38. Park K, Han S, Shin E, Kim H, Kim J. EGFR gene and protein expression in breast cancers. Eur J Surg Oncol. 2007;33:956-60 pubmed
    ..EGFR protein expression was independent of EGFR gene amplification status, whereas it was intimately associated with HER2 amplification and overexpression in breast cancer. ..
  39. Perez E, Suman V, Davidson N, Martino S, Kaufman P, Lingle W, et al. HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 intergroup adjuvant trial. J Clin Oncol. 2006;24:3032-8 pubmed
    ..These findings support the importance of using high-volume, experienced laboratories for HER2 testing to improve the process of selecting patients likely to benefit from trastuzumab therapy. ..
  40. Giuliani R, Durbecq V, Di Leo A, Paesmans M, Larsimont D, Leroy J, et al. Phosphorylated HER-2 tyrosine kinase and Her-2/neu gene amplification as predictive factors of response to trastuzumab in patients with HER-2 overexpressing metastatic breast cancer (MBC). Eur J Cancer. 2007;43:725-35 pubmed
    ..p-HER-2 and the magnitude of Her-2 amplification were predictive of response to T and their role deserves to be analysed in larger and more homogenous T-treated populations such as those from large phase III trials. ..
  41. Valabrega G, Montemurro F, Aglietta M. Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Ann Oncol. 2007;18:977-84 pubmed
  42. Laudadio J, Quigley D, Tubbs R, Wolff D. HER2 testing: a review of detection methodologies and their clinical performance. Expert Rev Mol Diagn. 2007;7:53-64 pubmed
    ..Thus, to offer prognostic information and to direct appropriate treatment it is important to provide accurate laboratory assessment of the status of HER2. This article provides an overview of the methods currently used to assess HER2. ..
  43. Wolff A, Hammond M, Schwartz J, Hagerty K, Allred D, Cote R, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25:118-45 pubmed
    ..The panel recommends that HER2 testing be done in a CAP-accredited laboratory or in a laboratory that meets the accreditation and proficiency testing requirements set out by this document. ..
  44. Reichelt U, Duesedau P, Tsourlakis M, Quaas A, Link B, Schurr P, et al. Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus. Mod Pathol. 2007;20:120-9 pubmed
    ..The strong concordance of the HER-2 status in primary and metastatic cancers argues for a possible response of metastases from patients with HER-2-positive primary tumors to Herceptin. ..
  45. Menendez J, Vazquez Martin A, Ropero S, Colomer R, Lupu R. HER2 (erbB-2)-targeted effects of the omega-3 polyunsaturated fatty acid, alpha-linolenic acid (ALA; 18:3n-3), in breast cancer cells: the "fat features" of the "Mediterranean diet" as an "anti-HER2 cocktail". Clin Transl Oncol. 2006;8:812-20 pubmed
  46. Wolf Yadlin A, Kumar N, Zhang Y, Hautaniemi S, Zaman M, Kim H, et al. Effects of HER2 overexpression on cell signaling networks governing proliferation and migration. Mol Syst Biol. 2006;2:54 pubmed
    ..Combining these modeling approaches enabled association of epidermal growth factor receptor family dimerization to activation of specific phosphorylation sites, which appear to most critically regulate proliferation and/or migration. ..
  47. Kanta S, Yamane T, Dobashi Y, Mitsui F, Kono K, Ooi A. Topoisomerase IIalpha gene amplification in gastric carcinomas: correlation with the HER2 gene. An immunohistochemical, immunoblotting, and multicolor fluorescence in situ hybridization study. Hum Pathol. 2006;37:1333-43 pubmed
    ..Therefore, results of the current study will provide further insight for the clinical application of anthracycline in gastric cancers. ..
  48. Woditschka S, Haag J, Waller J, Monson D, Hitt A, Brose H, et al. Neu-induced retroviral rat mammary carcinogenesis: a novel chemoprevention model for both hormonally responsive and nonresponsive mammary carcinomas. Cancer Res. 2006;66:6884-91 pubmed
    ..The model is useful for assessing the efficacy of chemopreventive agents, specifically those compounds that target hormonally nonresponsive tumors...
  49. Al Kuraya K, Novotny H, Bavi P, Siraj A, Uddin S, Ezzat A, et al. HER2, TOP2A, CCND1, EGFR and C-MYC oncogene amplification in colorectal cancer. J Clin Pathol. 2007;60:768-72 pubmed
    ..Although no molecular differences were found between incidences of colon cancer cases in Swiss and Saudi populations, these observations emphasise the urgent need for clinical studies investigating the effect of targeted therapies. ..
  50. Fischgräbe J, Wülfing P. Targeted therapies in breast cancer: established drugs and recent developments. Curr Clin Pharmacol. 2008;3:85-98 pubmed
    ..Due to the heterogeneity of disease and varying response to conventional systemic therapies, these new perceptions may lead to substantial patient benefit and provide a promising basis for future clinical application. ..
  51. de Roos M, van der Vegt B, de Vries J, Wesseling J, de Bock G. Pathological and biological differences between screen-detected and interval ductal carcinoma in situ of the breast. Ann Surg Oncol. 2007;14:2097-104 pubmed
    ..8; 95%CI 1.6-104.0; p = .018). These findings suggest that screen-detected DCIS is biologically more aggressive than interval DCIS and should not be regarded as overdiagnosis. ..
  52. Paiva C, Drigo S, Rosa F, Moraes Neto F, Caldeira J, Soares F, et al. Absence of transforming growth factor-beta type II receptor is associated with poorer prognosis in HER2-negative breast tumours. Ann Oncol. 2010;21:734-40 pubmed publisher
    ..These data indicate that TGF-betaRII protein analysis in tumour cells could be introduced in clinical practice as additional prognostic biomarker in HER2-negative BC. ..
  53. Flores L, Kindelberger D, Ligon A, Capelletti M, Fiorentino M, Loda M, et al. Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer. Br J Cancer. 2010;102:1495-502 pubmed publisher
    ..Circulating tumour cells obtained using CPK technology demonstrate that significant discordance exists between HER2 amplification of a patient's CTCs and that of the primary and metastatic tumour. ..