, Volume 12, Issue 7, pp 416–421

Détermination de HER2 dans les adénocarcinomes pour établir le pronostic et prédire la réponse aux traitements

  • P. Maroun
  • J. Gligorov
  • J. Ohnona
  • C. Murariu
  • Y. Belkacémi
Synthèse / Review Article


Les avancées enregistrées depuis la caractérisation des cibles jusqu’à l’utilisation des thérapies ciblées sont un modèle de développement de l’innovation en cancérologie. La surexpression de HER2 est considérée de façon très hétérogène selon le type de cancer au plan du pronostic et pour prédire la réponse à une thérapie ciblée. Dans le cancer du sein, la surexpression de HER2 a d’abord été considérée comme un facteur pronostique avant de révolutionner la stratégie thérapeutique de 20 % des patients. Dans les autres localisations, de nombreuses publications rapportent un intérêt pronostique de HER2, avec cependant un impact moindre en termes de prédiction de réponse au trastuzumab que dans le cancer du sein.

Mots clés

HER2 Cancer Pronostic Prédiction de réponse Trastuzumab 

Impact of HER2 status to define prognosis and to predict treatment efficacy in adenocarcinomas


The significant advances registered from targets definition to the use of targeted therapies are a model of innovative development in Oncology. HER2 overexpression has first been reported as prognostic factor before its consideration as a main parameter to predict treatment efficacy. In breast cancer HER2 determination is considered as a revolution for therapeutic strategy of about 15 to 20% of the patients. On the other hand, while HER2 is considered as a prognostic factor for many other cancers, its ability to predict efficacy of trastuzumab is much lower than in breast cancer.


HER2 Cancer Prognostic Prediction of response Trastuzumab 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Aigner A, Hsieh SS, Malerczyk C, Czubayko F (2000) Reversal of HER2 over-expression renders human ovarian cancer cells highly resistant to taxol. Toxicology 144: 221–228CrossRefPubMedGoogle Scholar
  2. 2.
    Bianco R, Shin I, Ritter CA, et al. (2003) Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine-kinase inhibitors. Oncogene 22: 2812–2822CrossRefPubMedGoogle Scholar
  3. 3.
    Bookman MA, Darcy KM, Clarke-Pearson D, et al. (2003) Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the Gynecologic Oncology Group. J Clin Oncol 21: 283–290CrossRefPubMedGoogle Scholar
  4. 4.
    Bunn PA Jr, Helfrich B, Soriano AF, et al. (2001) Expression of HER2/neu in human lung cancer cell lines by immunohistochemistry and fluorescence in situ hybridization and its relationship to in vitro cytotoxicity by trastuzumab and chemotherapeutic agents. Clin Cancer Res 7: 3239–3250PubMedGoogle Scholar
  5. 5.
    Carter P, Presta L, Gorman CM, et al. (1992) Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci U S A 89: 4285–4289CrossRefPubMedGoogle Scholar
  6. 6.
    Dahabreh IJ, Linardou H, Siannis F, et al. (2008) Trastuzumab in the adjuvant treatment of early-stage breast cancer: a systematic review and meta-analysis of randomized controlled trials. Oncologist 13: 620–630CrossRefPubMedGoogle Scholar
  7. 7.
    Dimova I, Zaharieva B, Raitcheva S, et al. (2006) Tissue microarray analysis of EGFR and erbB2 copy number changes in ovarian tumors. Int J Gynecol Cancer 16: 145–151CrossRefPubMedGoogle Scholar
  8. 8.
    Downward J, Yarden Y, Mayes E, et al. (1984) Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 307: 521–527CrossRefPubMedGoogle Scholar
  9. 9.
    El-Sahwi K, Bellone S, Cocco E, et al. (2010) In vitro activity of pertuzumab in combination with trastuzumab in uterine serous papillary adenocarcinoma. Br J Cancer 102: 134–143CrossRefPubMedGoogle Scholar
  10. 10.
    Fisher BJ, Perera FE, Cooke AL, et al. (1998) Long-term follow-up of axillary node-positive breast cancer patients receiving adjuvant tamoxifen alone: patterns of recurrence. Int J Radiat Oncol Biol Phys 42: 117–123PubMedGoogle Scholar
  11. 11.
    Fleming GF, Sill MW, Darcy KM, et al. (2010) Phase II trial of trastuzumab in women with advanced or recurrent, HER2-positive endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 116: 15–20CrossRefPubMedGoogle Scholar
  12. 12.
    Gatzemeier U, Groth G, Butts C, et al. (2004) Randomized phase II trial of gemcitabine/cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer. Ann Oncol 15: 3–4CrossRefGoogle Scholar
  13. 13.
    Gieseg MA, de Bock C, Ferguson LR et al. (2001) Evidence for epidermal growth factor receptor-enhanced chemosensitivity in combinations of cisplatin and the new irreversible tyrosine-kinase inhibitor CI-1033. Anticancer Drugs 12: 683–690CrossRefPubMedGoogle Scholar
  14. 14.
    Goldhirsch A, Wood WC, Gelber RD, et al. (2007) Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer. Ann Oncol 18: 1133–1144CrossRefPubMedGoogle Scholar
  15. 15.
    Grabsch H, Sivakumar S, Gray S, et al. (2010) HER2 expression in gastric cancer: rare, heterogeneous and of no prognostic value — conclusions from 924 cases of two independent series. Cell Oncol 32: 57–65PubMedGoogle Scholar
  16. 16.
    Gravalos C, Jimeno A (2008) HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol 19: 1523–1529CrossRefPubMedGoogle Scholar
  17. 17.
    Gusterson BA, Gelber RD, Goldhirsch A, et al. (1992) Prognostic importance of c-erbB-2 expression in breast cancer. International (Ludwig) Breast Cancer Study Group. J Clin Oncol 10: 1049–1056PubMedGoogle Scholar
  18. 18.
    Han H, Landreneau RJ, Santucci TS, et al. (2002) Prognostic value of immunohistochemical expressions of p53, HER2/neu, and bcl-2 in stage I non-small-cell lung cancer. Hum Pathol 33: 105–110CrossRefPubMedGoogle Scholar
  19. 19.
    Hansel DE, Ashfaq R, Rahman A, et al. (2005) A subset of pancreatic adenocarcinomas demonstrates coamplification of topoisomerase II alpha and HER2/neu: use of immunolabeling and multicolor FISH for potential patient screening and treatment. Am J Clin Pathol 123: 28–35CrossRefPubMedGoogle Scholar
  20. 20.
    Hayashi M, Inokuchi M, Takagi Y, et al. (2008) High expression of HER3 is associated with a decreased survival in gastric cancer. Clin Cancer Res 14: 7843–7849CrossRefPubMedGoogle Scholar
  21. 21.
    Hortobagyi G (2005) Trastuzumab in the treatment of breast cancer. N Engl J Med 353: 1734–1736CrossRefPubMedGoogle Scholar
  22. 22.
    Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. (2006) Trastuzumab in combination with docetaxel or vinorelbine as adjuvat treatment of breast cancer: the FinHer trial. N Engl J Med 354: 809–820CrossRefPubMedGoogle Scholar
  23. 23.
    Jøorgensen JT (2010) Targeted HER2 treatment in advanced gastric cancer. Oncology 78: 26–33CrossRefGoogle Scholar
  24. 24.
    Junker K, Stachetzki U, Rademacher D, et al. (2005) HER2/neu expression and amplification in non-small cell lung cancer prior to and after neoadjuvant therapy. Lung Cancer 48: 59–67CrossRefPubMedGoogle Scholar
  25. 25.
    Konecny GE, Santos L, Winterhoff B, et al. (2009) HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer. Br J Cancer 100: 89–95CrossRefPubMedGoogle Scholar
  26. 26.
    Langer CJ, Stephenson P, Thor A, et al. (2004) Trastuzumab in the treatment of advanced non-small-cell lung cancer: is there a role? Focus on Eastern Cooperative Oncology Group study 2598. J Clin Oncol 22: 1171–1173CrossRefGoogle Scholar
  27. 27.
    Larbouret C, Robert B, Teulon I, et al. (2007) Combined anti-EGFR and anti-HER2 monoclonal antibodies: preclinical efficacy in the treatment of pancreatic cancer. Med Sci (Paris) 23: 800–803Google Scholar
  28. 28.
    Marty M, Cognetti F, Maraninchi D, et al. (2005) Efficacy and safety of trastuzumab combined with docetaxel in patients with HER2-positive metastatic breast cancer given as first-line treatment: results of a randomized phase II trial (M77001). J Clin Oncol 23: 4265–4274CrossRefPubMedGoogle Scholar
  29. 29.
    Matsui Y, Inomata M, Tojigamori M, et al. (2005) Suppression of tumor growth in human gastric cancer with HER2 overexpression by an anti-HER2 antibody in a murine model. Int J Oncol 27: 681–685PubMedGoogle Scholar
  30. 30.
    Meert AP, Martin B, Paesmans M, et al. (2003) The role of HER2/neu expression on the survival of patients with lung cancer: A systematic review of the literature. Br J Cancer 89: 959–965CrossRefPubMedGoogle Scholar
  31. 31.
    Mehta K, Haffty BG (1996) Long-term outcome in patients with four or more positive lymph nodes treated with conservative surgery and radiation therapy. Int J Radiat Oncol Biol Phys 35: 679–685PubMedGoogle Scholar
  32. 32.
    Meza-Junco J, Au HJ, Sawyer MB (2009) Trastuzumab for gastric cancer. Expert Opin Biol Ther 9: 1543–1551CrossRefPubMedGoogle Scholar
  33. 33.
    Mulligan AM, Pinnaduwage D, Bull SB, et al. (2008) Prognostic effect of basal-like breast cancers is time dependent: evidence from tissue microarray studies on a lymph node-negative cohort. Clin Cancer Res 14: 4168–4174CrossRefPubMedGoogle Scholar
  34. 34.
    Namer M, Gligorov J, Luporsi E, et al. (2007) Recommandations pour la pratique clinique de Saint Paul de Vence. Oncologie 9: 593–644CrossRefGoogle Scholar
  35. 35.
    Perou CM, Sorlie T, Eisen MB, et al. (2000) Molecular portraits of human breast tumours. Nature 406: 747–752CrossRefPubMedGoogle Scholar
  36. 36.
    Piccart-Gebhart M, Procter M, Leyland-Jones B, et al. (2005) Trastuzumab after adjuvant chemotherapy for HER2-positive breast cancer. N Engl J Med 353: 1659–1672CrossRefPubMedGoogle Scholar
  37. 37.
    Pils D, Pinter A, Reibenwein J, et al. (2007) In ovarian cancer the prognostic influence of HER2/neu is not dependent on the CXCR4/SDF-1 signalling pathway. Br J Cancer 96: 485–491CrossRefPubMedGoogle Scholar
  38. 38.
    Ravdin PM, Siminoff LA, Davis GJ, et al. (2001) Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol 19: 980–991PubMedGoogle Scholar
  39. 39.
    Romond EH, Perez EA, Bryant J, et al. (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353: 1673–1684CrossRefPubMedGoogle Scholar
  40. 40.
    Santin AD, Bellone S, Roman JJ, et al. (2008)Trastuzumab treatment in patients with advanced or recurrent endometrial carcinoma overexpressing HER2/neu. Int J Gynaecol Obstet. 102(2): 128–131 [Epub 2008 Jun 16]CrossRefPubMedGoogle Scholar
  41. 41.
    Schmoor C, Sauerbrei W, Bastert G, et al. (2001) Long-term prognosis of breast cancer patients with 10 or more positive lymph nodes treated with CMF. Eur J Cancer 37: 1123–1131CrossRefPubMedGoogle Scholar
  42. 42.
    Serrano-Olvera A, Duenas-Gonzalez A, Gallardo-Rincon D, et al. (2006) Prognostic, predictive and therapeutic implications of HER2 in invasive epithelial ovarian cancer. Cancer Treat Rev 32: 180–190CrossRefPubMedGoogle Scholar
  43. 43.
    Sharif S, Ramanathan RK, Potter D, et al. (2008) HER2 gene amplification and chromosome 17 copy number do not predict survival of patients with resected pancreatic adenocarcinoma. Dig Dis Sci 53: 3026–3032CrossRefPubMedGoogle Scholar
  44. 44.
    Slamon D (2005) Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC-T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC-TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2 positive early breast cancer patients: BCIRG 006 study. Breast Cancer Res Treat 91: 1 [abstract]CrossRefGoogle Scholar
  45. 45.
    Slamon DJ, Clark GM, Wong SG, et al. (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science 235: 177–182CrossRefPubMedGoogle Scholar
  46. 46.
    Slamon DJ, Leyland-Jones B, Shak S, et al. (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344: 783–792CrossRefPubMedGoogle Scholar
  47. 47.
    Soerjomataram I, Louwman MW, Ribot JG, et al. (2008) An overview of prognostic factors for long-term survivors of breast cancer. Breast Cancer Res Treat 107: 309–330CrossRefPubMedGoogle Scholar
  48. 48.
    Stoecklein NH, Luebke AM, Erbersdobler A, et al. (2004) Copy number of chromosome 17 but not HER2 amplification predicts clinical outcome of patients with pancreatic ductal adenocarcinoma. J Clin Oncol 22: 4737–4745CrossRefPubMedGoogle Scholar
  49. 49.
    Tsai CM, Chang KT, Perng RP, et al. (1993) Correlation of intrinsic chemoresistance of non-small-cell lung cancer cell lines with HER2/neu gene expression but not with ras gene mutations. J Natl Cancer Inst 85: 897–901CrossRefPubMedGoogle Scholar
  50. 50.
    Tuefferd M, Couturier J, Penault-Llorca F, et al. (2007) HER2 status in ovarian carcinomas: a multicenter GINECO study of 320 patients. PLoS One 2: e1138CrossRefPubMedGoogle Scholar
  51. 51.
    Verri E, Guglielmini P, Puntoni M, et al. (2005) HER2/neu oncoprotein overexpression in epithelial ovarian cancer: evaluation of its prevalence and prognostic significance. Clinical study. Oncology 68: 154–161Google Scholar
  52. 52.
    Wainberg ZA, Anghel A, Desai AJ, et al. (2010) Lapatinib, a dual EGFR and HER2 kinase inhibitor, selectively inhibits HER2-amplified human gastric cancer cells and is synergistic with trastuzumab in vitro and in vivo. Clin Cancer Res 16(5): 1509–1519CrossRefPubMedGoogle Scholar
  53. 53.
    Wolff AC, Hammond ME, Schwartz JN, et al. (2007) 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 25: 118–145CrossRefPubMedGoogle Scholar
  54. 54.
    Wright C, Nicholson S, Angus B, et al. (1992) Relationship between c-erbB-2 protein product expression and response to endocrine therapy in advanced breast cancer. Br J Cancer 65: 118–121PubMedGoogle Scholar
  55. 55.
    Yu GZ, Chen Y, Wang JJ (2009) Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance. J Cancer Res Clin Oncol 135: 1331–1339CrossRefPubMedGoogle Scholar
  56. 56.
    Zhang XL, Yang YS, Xu DP, et al. (2009) Comparative study on overexpression of HER2/neu and HER3 in gastric cancer. World J Surg 33: 2112–2118CrossRefPubMedGoogle Scholar

Copyright information

© Springer Verlag France 2010

Authors and Affiliations

  • P. Maroun
    • 1
    • 2
  • J. Gligorov
    • 3
  • J. Ohnona
    • 1
    • 2
  • C. Murariu
    • 1
    • 2
  • Y. Belkacémi
    • 1
    • 2
  1. 1.Service d’oncologie-radiothérapiehôpital Henri-MondorCréteilFrance
  2. 2.Faculté de médecine de Créteiluniversité de Paris-XIICréteil cedexFrance
  3. 3.Service d’oncologie médicale, hôpital Tenon, AP-HP, Cancer-Estuniversité de Paris-VIParisFrance

Personalised recommendations