HER2 and gastric cancer: A novel therapeutic target for trastuzumab;HER2 et cancer de l'estomac: Une nouvelle cible thérapeutique pour le trastuzumab

Bulletin du Cancer

Volumn 97, Issue 12, 2010, Pages 1429-1440

  Bouche O ^a   Penault Llorca, F ^b  

^a SERVICE DE DERMATOLOGIE   (France)

^b CENTRE JEAN PERRIN   (France)

Author keywords

erbB 2; FISH (fluorescent in situ hybridization); Gastric cancer; Gastroesophageal adenocarcinoma; HER2; Immunohistochemistry; Targeted therapy; Trastuzumab; Treatment

Indexed keywords

CAPECITABINE; CISPLATIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; FLUOROURACIL; TRASTUZUMAB; ANTINEOPLASTIC AGENT; DEOXYCYTIDINE; DRUG DERIVATIVE; HER2 PROTEIN, HUMAN; MONOCLONAL ANTIBODY; PARAFFIN;

CANCER COMBINATION CHEMOTHERAPY; DRUG EFFICACY; DRUG TARGETING; ESOPHAGUS CANCER; GASTROESOPHAGEAL JUNCTION CANCER; GENE OVEREXPRESSION; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; METASTASIS; MONOTHERAPY; OVERALL SURVIVAL; RANDOMIZED CONTROLLED TRIAL; REVIEW; STOMACH ADENOCARCINOMA; STOMACH BIOPSY; STOMACH CANCER; CHEMISTRY; DRUG ANTAGONISM; DRUG CONTRAINDICATION; IN SITU HYBRIDIZATION; LOWER ESOPHAGUS SPHINCTER; METHODOLOGY; RANDOMIZED CONTROLLED TRIAL (TOPIC); STOMACH TUMOR;

ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CISPLATIN; DEOXYCYTIDINE; ESOPHAGOGASTRIC JUNCTION; FLUOROURACIL; HUMANS; IMMUNOHISTOCHEMISTRY; IN SITU HYBRIDIZATION; PARAFFIN EMBEDDING; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RECEPTOR, ERBB-2; STOMACH NEOPLASMS;

EID: 79251518952     PISSN: 00074551     EISSN: 17696917     Source Type: Journal    
DOI: 10.1684/bdc.2010.1224     Document Type: Review

References (97)

1. Fuchs CS, Mayer RJ. Gastric carcinoma. New Engl J Med 1995;333:32-41.
2. Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol 2006;12:354-62.
3. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006;24:2137-50.
4. Guérin S, Hill C. L'épidémiologie des cancers en France en 2010: comparaison avec les États-Unis. Bull Cancer 2010;97:47-63.
5. El-Serag HB, Mason AC, Petersen N, Key CR. Epidemiological differences between adenocarcinoma of the oesophagus and adenocarcinoma of the gastric cardia in the USA. Gut 2002;50:368-72.
6. Blot WJ, Devesa SS, Kneller RW, Fraumeni Jr JF. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 1991;265:1287-9.
7. Bouvier AM, Esteve J, Mitry E, Clinard F, Bonithon-Kopp C, Faivre J. Trends in gastric cancer incidence in a well-defined French population by time period and birth cohort. Eur J Cancer Prev 2002;11:221-7.
8. Fayçal J, Bessaguet C, Nousbaum JB, Cauvin JM, Cholet F, Bideau K, et al. Epidemiology and long term survival of gastric carcinoma in the French area of Finistere between 1984 and 1995. Gastroenterol Clin Biol 2005;29:23-32.
9. Henson DE, Dittus C, Younes M, Nguyen H, Albores-Saavedra J. Differential trends in the intestinal and diffuse types of gastric carcinoma in the United States, 1973-2000: increase in the signet ring cell type. Arch Pathol Lab Med 2004;128:765-70.
10. Lauren T. The two histologic main type of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 1965;64:31-49.
11. e vol. Lyon: IARC scientific publications, 1994.
12. Courillon-Mallet A. Helicobacter pylori and gastric cancer: eradication to prevent cancer? Gastroenterol Clin Biol 2009;33:301-5.
13. Correa P, Houghton J. Carcinogenesis of Helicobacter pylori. Gastroenterology 2007;133:659-72.
14. Msika S, Benhamiche AM, Jouve JL, Rat P, Faivre J. Prognostic factors after curative resection for gastric cancer. A populationbased study. Eur J Cancer 2000;36:390-6.
15. Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev 2010: CD004064.
16. Thésaurus national de cancérologie digestive [en ligne]: http://www.snfge.asso.fr/01-Bibliotheque/0G-Thesaurus-cancerologie/publication5/ sommaire-thesaurus.asp (consulté le 20 octobre 2010).
17. Schechter AL, Stern DF, Vaidyanathan L, Decker SJ, Drebin JA, Greene MI, et al. The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature 1984;312:513-6.
18. Schechter AL, Hung MC, Vaidyanathan L, Weinberg RA, Yang-Feng TL, Francke U, et al. The neu gene:an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science 1985;229:976-8.
19. Das M, Miyakawa T, Fox CF, Pruss RM, Aharonov A, Herschman HR, et al. Specific radiolabeling of a cell surface receptor for epidermal growth factor. Proc Natl Acad Sci USA 1977;74:2790-4.
20. Akiyama T, Sudo C, Ogawara H, Toyoshima K, Yamamoto T. The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine-kinase activity. Science 1986;232:1644-6.
21. Baeckstrom D, Alford D, Taylor-Papadimitriou J. Morphogenetic and proliferative responses to heregulin of mammary epithelial cells in vitro are dependent on HER2 and HER3 and differ from the responses to HER2 homodimerisation or hepatocyte growth factor. Int J Oncol 2000;16:1081-90.
22. King CR, Kraus MH, Aaronson SA. Amplification of a novel verbB-related gene in a human mammary carcinoma. Science 1985;229:974-6.
23. Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, et al. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature 1986;319:230-4. (Pubitemid 16128786)
24. Yokota J, Yamamoto T, Toyoshima K, Terada M, Sugimura T, Battifora H, et al. Amplification of cerbB-2 oncogene in human adenocarcinomas in vivo. Lancet 1986;1:765-7.
25. Yonemura Y, Ninomiya I, Yamaguchi A, Fushida S, Kimura H, Ohoyama S, et al. Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. Cancer Res 1991;51:1034-8.
26. Mizutani T, Onda M, Tokunaga A, Yamanaka N, Sugisaki Y. Relationship of C-erbB-2 protein expression and gene amplification to invasion and metastasis in human gastric cancer. Cancer 1993;72:2083-8.
27. Uchino S, Tsuda H, Maruyama K, Kinoshita T, Sasako M, Saito T, et al. Overexpression of c-erbB-2 protein in gastric cancer. Cancer 1993;2:3179-84.
28. Motojima K, Furui J, Kohara N, Izawa K, Kanematsu T, Shiku H. ErbB-2 expression in well-differentiated adenocarcinoma of the stomach predicts shorter survival after curative resection. Surgery 1994;115:349-54.
29. Nakajima M, Sawada H, Yamada Y, Watanabe A, Tatsumi M, Yamashita J, et al. The prognostic significance of amplification and overexpression of c-met and c-erbB-2 in human gastric carcinomas. Cancer 1999;85:1894-902.
30. Allgayer H, Babic R, Gruetzner KU, Tarabichi A, Schildberg FW, Heiss MM. C-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumorassociated protease systems. J Clin Oncol 2000;18:2201-9.
31. Pinto-de-Sousa J, David L, Almeida R, Leitão D, Preto JR, Seixas M, et al. C-erbB-2 expression is associated with tumor location and venous invasion and influences survival of patients with gastric carcinoma. Int J Surg Pathol 2002;10:247-56.
32. García I, Vizoso F, Martín A, Sanz L, Abdel-Lah O, Raigoso P, et al. Clinical significance of the epidermal growth factor receptor and HER2 receptor in resectable gastric cancer. Ann Surg Oncol 2003;10:234-41. (Pubitemid 40486955)
33. Tanner M, Hollmén M, Junttila TT, Kapanen AI, Tommola S, Soini Y, et al. Amplification of HER2 in gastric carcinoma: association with topoisomerase II alpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol 2005;16:273-8.
34. Park DI, Yun JW, Park JH, Oh SJ, Kim HJ, Cho YK, et al. HER2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci 2006;51:1371-9.
35. Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol 2008;19:1523-9.
36. Zhang XL, Yang YS, Xu DP, Qu JH, Guo MZ, Gong Y, et al. Comparative study on overexpression of HER2/neu and HER3 in gastric cancer. World J Surg 2009;33:2112-8.
37. Yan B, Yau EX, Bte Omar SS, Ong CW, Pang B, Yeoh KG, et al. A study of HER2 gene amplification and protein expression in gastric cancer. J Clin Pathol 2010;63:839-42.
38. Tateishi M, Toda T, Minamisono Y, Nagasaki S. Clinicopathological significance of c-erbB-2 protein expression in human gastric carcinoma. J Surg Oncol 1992;49:209-12.
39. Ohguri T, Sato Y, Koizumi W, Saigenji K, Kameya T. An immunohistochemical study of c-erbB-2 protein in gastric carcinomas and lymph-node metastases: is the c-erbB-2 protein really a prognostic indicator? Int J Cancer 1993;53:75-9.
40. Lee HR, Kim JH, Uhm HD, Ahn JB, Rha SY, Cho JY, et al. Overexpression of c-ErbB-2 protein in gastric cancer by immunohistochemical stain. Oncology 1996;53:192-7.
41. Grabsch H, Sivakumar S, Gray S, Gabbert HE, Muller W. 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.
42. Marx AH, Tharun L, Muth J, Dancau AM, Simon R, Yekebas E, et al. HER2 amplification is highly homogenous in gastric cancer. Hum Pathol 2009;40:769-77.
43. Risio M, De Rosa G, Sarotto I, Casorzo L, Capussotti L, Torchio B, et al. HER2 testing in gastric cancer: molecular morphology and storage time-related changes in archival samples. Int J Oncol 2003;23:1381-7.
44. Kasprzyk PG, Song SU, Di Fiore PP, King CR. Therapy of an animal model of human gastric cancer using a combination of anti-erbB-2 monoclonal antibodies. Cancer Res 1992;52:2771-6.
45. Carter P, Presta L, Gorman CM, Ridgway JB, Henner D, Wong WL, et al. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci USA 1992;89:4285-9.
46. Hudis CA. Trastuzumab-mechanism of action and use in clinical practice. N Engl J Med 2007;357:39-51.
47. Matsui Y, Inomata M, Tojigamori M, Sonoda K, Shiraishi N, Kitano S, et al. Suppression of tumor growth in human gastric cancer with HER2 overexpression by an anti-HER2 antibody in a murine model. Int J Oncol 2005;27:681-5.
48. Fujimoto-Ouchi K, Sekiguchi F, Yasuno H, Moriya Y, Mori K, Tanaka Y, et al. Antitumor activity of trastuzumab in combination with chemotherapy in human gastric cancer xenograft models. Cancer Chemother Pharmacol 2007;59:795-805.
49. Nicholas G, Cripps C, Au H-J, Jonker D, Salim M, Bjarnason G, et al. Early results of a trial of trastuzumab, cisplatin, and docetaxel (TCD) for the treatment of metastatic gastric cancer overexpressing HER2 (abstract). Ann Oncol 2006;17(Suppl 9):1105a.
50. Rech J, Arnold D, Folprecht G, Hejna M, Hofmann M, Gramatzki M. A pilot study of trastuzumab monotherapy in patients who progressed while on chemotherapy for metastatic or locally advanced HER2+ gastric cancer (abstract). Ann Oncol 2006;17(Suppl 9):1096a.
51. Cortes-Funes H, Rivera F, Ales I, Márquez A, Velasco A, Colomer R, et al. Phase II of trastuzumab and cisplatin in patients (pts) with advanced gastric cancer with HER2/neu overexpression/amplification (abstract). J Clin Oncol 2007;15:4613a.
52. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy vs chemotherapy alone for treatment of HER2+ advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010;376:687-97.
53. Piessen G, Messager M, Leteurtre E, Jean-Pierre T, Mariette C. Signet ring cell histology is an independent predictor of poor prognosis in gastric adenocarcinoma regardless of tumoral clinical presentation. Ann Surg 2009;250:878-87.
54. Yamashita K, Sakuramoto S, Katada N, Futawatari N, Moriya H, Hirai K, et al. Diffuse type advanced gastric cancer showing dismal prognosis is characterized by deeper invasion and emerging peritoneal cancer cell: the latest comparative study to intestinal advanced gastric cancer. Hepatogastroenterology 2009;56:276-81.
55. Zheng H, Takahashi H, Murai Y, Cui Z, Nomoto K, Miwa S, et al. Pathobiological characteristics of intestinal and diffuse-type gastric carcinoma in Japan: an immunostaining study on the tissue microarray. J Clin Pathol 2007;60:273-7.
56. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, 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.
57. DiVito KA, Charette LA, Rimm DL, Camp RL. Long term preservation of antigenicity on tissue microarrays. Lab Invest 2004;84:1071-8.
58. Atkins D, Reiffen KA, Tegtmeier CL, Winther H, Bonato MS, Störkel S. Immunohistochemical detection of EGFR in paraffinembedded tumor tissues: variation in staining intensity due to choice of fixative and storage time of tissue sections. J Histochem Cytochem 2004;52:893-901.
59. Recommandations de Bonnes Pratiques en ACP: (available from http://www.afaqap.org/ecrire/upload/201001181206340. RBPACP%20v2-2009-web.pdf.
60. Rüschoff J, Dietel M, Baretton G, Arbogast S, Walch A, Monges G, et al. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch 2010;457:299-307.
61. Park YS, Jang SJ, Park HJ, Ryu M, Ryoo B, Yook JH, et al. HER2 overexpression and gene amplification in gastric cancer (abstract). Ann Oncol 2010;21(Suppl 8):822.
62. Penault-Llorca F, Bilous M, Dowsett M, Hanna W, Osamura RY, Rüschoff J, et al. Emerging technologies for assessing HER2 amplification. Am J Clin Pathol 2009;132:539-48.
63. Papouchado BG, Myles J, Lloyd RV, Stoler M, Oliveira AM, Downs-Kelly E, et al. Silver in situ hybridization (SISH) for determination of HER2 gene status in breast carcinoma: comparison with FISH and assessment of interobserver reproducibility. Am J Surg Pathol 2010;34:767-76.
64. Powell WC, Zielinski D, Ranger-Moore J, Nagelmeier I, Stoss O, Ruschoff J, et al. Determining the HER2 status in gastric cancer: method comparison study of two patient cohorts (abstract). Presented at 2010 Gastrointestinal Cancers Symposium, January 2010, Available at http://www asco org. Accessed 25 october 2010. ASCO GI 2010:17a.
65. http://www.ema.europa.eu/docs/fr-FR/document-library/EPAR-Product- Information/human/000278/WC500074922.pdf.
66. Hofmann M, Stoss O, Shi D, Büttner R, Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 2008;52:797-805.
67. Bang Y, Chung H, Xu J, Lordick F, Sawaki A, Al-Sakaff N, et al. Pathological features of advanced gastric cancer (GC): relationship to human epidermal growth factor receptor 2 positivity in the global screening programme of the ToGA trial (abstract). J Clin Oncol 2009;27(Suppl 15 s): 4556a.
68. Yu GZ, Chen Y, Wang JJ. Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance. J Cancer Res Clin Oncol 2009;135:1331-9.
69. Negri FV, Bozzetti C, Lagrasta C, Crafa P, Nizzoli R, Leonardi F, et al. HER2 status in primary and paired distant metastatic sites of gastric carcinoma (abstract). Ann Oncol 2010;21(Suppl 8):823.
70. EMEA, European Medicines Agency (2009): opinion www.emea.europa.eu/pdfs/ human/opinion/Herceptin-82246709en.pdf.
71. http://www.cancer.gov/cancertopics/druginfo/fda-trastuzumab - Anchor-Gastric.
72. http://guidance.nice.org.uk/TA/Wave19/63.
73. Okines A, Verheij M, Allum W, Cunningham D, Cervantes A, ESMO Guidelines Working Group. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21(Suppl 5): v50-v4.
74. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 2008;358:36-46.
75. Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, et al. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol 2008;26:1435-42.
76. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, 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.
77. Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol 2005;23:4265-74.
78. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al. Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2+ breast cancer. N Engl J Med 2005;353:1659-72.
79. Mani A, Roda J, Young D, Caligiuri MA, Fleming GF, Kaufman P, et al. A phase II trial of trastuzumab in combination with low-dose interleukin-2 (IL-2) in patients (PTS) with metastatic breast cancer (MBC) who have previously failed trastuzumab. Breast Cancer Res Treat 2009;117:83-9.
80. Loesch D, Asmar L, McIntyre K, Doane L, Monticelli M, Paul D, et al. Phase II trial of gemcitabine/carboplatin (plus trastuzumab in HER2+ disease) in patients with metastatic breast cancer. Clin Breast Cancer 2008;8:178-86.
81. Kim SY, Kim HP, Kim YJ, Oh do Y, Im SA, 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
82. Yardley DA, Daniel D, Stipanov M, Drosick DR, Mainwaring M, Peyton J, et al. A phase II trial of oxaliplatin and trastuzumab in the treatment of HER2+ metastatic breast cancer. Cancer Invest 2010;28:865-71.
83. Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 2002;20:1215-21.
84. Campone M, Bourbouloux E, Fumoleau P. Cardiac dysfunction induced by trastuzumab. Bull Cancer 2004;91(Suppl 3):166-73.
85. Telli ML, Hunt SA, Carlson RW, Guardino AE. Trastuzumabrelated cardiotoxicity: Calling into question the concept of reversibility. J Clin Oncol 2007;25:3525-33.
86. Cardinale D, Colombo A, Torrisi R, Sandri MT, Civelli M, Salvatici M, et al. Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation. J Clin Oncol 2010;28:3910-6.
87. Wang J, Saukel GW, Garberoglio CA, Srikureja W, Hsueh CT. Pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen in gastric cancer: a case report. J Hematol Oncol 2010;3:31.
88. Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2+ advanced breast cancer. New Engl J Med 2006;355:2733-43.
89. Kim JW, Kim HP, Im SA, Kang S, Hur HS, Yoon YK, et al. The growth inhibitory effect of lapatinib, a dual inhibitor of EGFR and HER2 tyrosine-kinase, in gastric cancer cell lines. Cancer Lett 2008;272:296-306.
90. LaBonte MJ, Manegold PC, Wilson PM, Fazzone W, Louie SG, Lenz HJ, et al. The dual EGFR/HER2 tyrosine-kinase inhibitor lapatinib sensitizes colon and gastric cancer cells to the irinotecan active metabolite SN-38. Int J Cancer 2009;125:2957-69.
91. Wainberg ZA, Anghel A, Desai AJ, Ayala R, Luo T, Safran B, et al. 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 2010;16:1509-19.
92. Iqbal S, Goldman B, Lenz HJ, Fenoglio-Preiser CM, Blanke CD. S0413: a phase II SWOG study of GW572016 (lapatinib) as firstline therapy in patients with advanced or metastatic gastric cancer (abstract). J Clin Oncol 2007;25:4621a.
93. Hecht JR, Urba SG, Koehler M, Ellis C, Gagnon R, Kemner A, et al. Lapatinib monotherapy in recurrent upper gastrointestinal malignancy: phase II efficacy and biomarker analyses (abstract). Presented at 2008 Gastrointestinal Cancers Symposium, January 2008, Available at http://www asco org. Accessed 4november 2010. ASCO GI 2008:43a.
94. Baselga J, Gelmon KA, Verma S, Wardley A, Conte P, Miles D, et al. Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol 2010;28:1138-44.
95. Wynne C, Harvey V, Schwabe C, Waaka D, McIntyre C, Bittner B. The development of a formulation of trastuzumab for subcutaneous administration (abstract). Ann Oncol 2010;21(Suppl 8):218PD.
96. Krop IE, Beeram M, Modi S, Jones SF, Holden SN, Yu W, et al. Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2+ metastatic breast cancer. J Clin Oncol 2010;28:2698-704.
97. Perez E, Dirix L, Kocsis J, Gianni L, Lu J, Vinholes J, et al. Efficacy and safety of trastuzumab-DM1 vs trastuzumab plus docetaxel in HER2+ metastatic breast cancer patients with no prior chemotherapy for metastatic disease: preliminary results of a randomized, multicenter, open-label phase 2 study (TDM4450G) (abstract). Ann Oncol 2010;21(Suppl 8): LBA3.