Tumor-associated antigens and biomarkers in cancer and immune therapy

International Reviews of Immunology

Volumn 26, Issue 3-4, 2007, Pages 223-247

  Malyankar, Uriel M ^a  

^a MannKind Corporation   (United States)

Author keywords

Biomarker; Genomics; Immune therapy; Proteomics; Tumor associated antigen

Indexed keywords

ALEMTUZUMAB; BEVACIZUMAB; BIOLOGICAL MARKER; CETUXIMAB; DOCETAXEL; FLUOROURACIL; IBRITUMOMAB TIUXETAN; NAKED DNA; PANITUMUMAB; PEPTIDE; PROTEIN; RECOMBINANT PROTEIN; RITUXIMAB; TOPOTECAN; TOSITUMOMAB; TRASTUZUMAB; TUMOR ANTIGEN; VACCINE;

ACTIVE IMMUNIZATION; BREAST CANCER; CANCER; CANCER IMMUNOTHERAPY; CELL THERAPY; CHRONIC LYMPHATIC LEUKEMIA; COLORECTAL CANCER; DIAGNOSIS; DISEASE MARKER; ESOPHAGUS CANCER; GENE EXPRESSION; GENETIC ANALYSIS; GENOMICS; HEAD AND NECK CANCER; HUMAN; HUMORAL IMMUNITY; IMMUNE SYSTEM; KIDNEY CANCER; LUNG ADENOCARCINOMA; LUNG NON SMALL CELL CANCER; MELANOMA; METABOLOMICS; NONHODGKIN LYMPHOMA; NONHUMAN; OVARY CANCER; PASSIVE IMMUNIZATION; POPULATION; PRIORITY JOURNAL; PROGNOSIS; PROSTATE TUMOR; PROTEOMICS; REVIEW; SQUAMOUS CELL CARCINOMA; THERAPY;

ANTIBODIES, MONOCLONAL; ANTIGENS, NEOPLASM; CLINICAL TRIALS; HUMANS; IMMUNOTHERAPY; IMMUNOTHERAPY, ACTIVE; NEOPLASMS; SIGNAL TRANSDUCTION; TUMOR MARKERS, BIOLOGICAL;

EID: 34250178451     PISSN: 08830185     EISSN: 15635244     Source Type: Journal    
DOI: 10.1080/08830180701402496     Document Type: Review

References (106)

1. D. Thomson, The carcinoembryonic antigen (CEA) radioimmunoassay. Proc. R. Soc. Med., 65: 635-636, 1972.
2. W.S. Dalton and S.H. Friend, Cancer biomarkers-an invitation to the table. Science, 312(5777): 1165-1168, 2006.
3. C.F. Basil, Y. Zhao, K. Zavaglia, et al., Common cancer biomarkers, Cancer Res., 66: 2953-2961, 2006.
4. P.S. Nelson, Identifying immunotherapeutic targets for prostate carcinoma through the analysis of gene expression profiles, Ann. N. Y. Acad. Sci., 975: 232-246, 2002.
5. A.M. Glas, A. Floore, L.J. Delahaye, et al., Converting a breast cancer microarray signature into a high-throughput diagnostic test, BMC Genomics, 7: 278, 2006.
6. T. Olafsen, V.E. Kenanova, G. Sundaresan, et al., Optimizing radiolabeled engineered anti-p185HER2 antibody fragments for in vivo imaging, Cancer Res., 65(13): 5907-5916, 2005.
7. L.K. Mattison, J. Fourie, Y. Hirao, et al., The uracil breath test in the assessment of dihydropyrimidine dehydrogenase activity: Pharmacokinetic relationship between expired 13CO2 and plasma [2-13C]Dihydrouracil, Clin. Cancer Res., 12(2): 549-555, 2006.
8. P. Duramad, C.W. McMahon, A. Hubbard, et al., Flow cytometric detection of intracellular Th1/Th2 cytokines using whole blood: Validation of immunologic biomarker for use in epidemiologic studies, Cancer Epidemiol Biomarkers Prev., 13(9): 1452-1458, 2004.
9. C.B. Ambrosone, Sample collection, processing, and storage for large-scale studies: Biorepositories to support cancer research, Cancer Epidemiol Biomarkers Prev., 15: 1574, 2006.
10. D.F. Ransohoff, Bias as a threat to the validity of cancer molecular-marker research, Nat. Rev. Cancer, 5(2): 142-149, 2005.
11. M.J. Fackler, M. McVeigh, J. Mehrotra, et al., Quantitative multiplex methylation-specific PCR assay for the detection of promoter hypermethylation in multiple genes in breast cancer, Cancer Res., 64(13): 4442-4452, 2004.
12. D.E. Bassett, M.B. Eisen, and M.S. Boguski, Gene expression informatics [mdash]it's all in your mine, Nature Genetics, 21(1): 51-55, 1999.
13. A. Schumacher, P. Kapranov, Z. Kaminsky, et al., Microarray-based DNA methylation profiling: Technology and applications, Nucleic Acids Res., 34: 528-542, 2006.
14. A. Butte, The use and analysis of microarray data, Nat. Rev. Drug Discov., 1: 951-960, 2002.
15. A. Brazma, P. Hingamp, J. Quackenbush, et al., Minimum information about a microarray experiment (MIAME)[-]toward standards for microarray data, Nature Genetics, 29(4): 365-371, 2001.
16. T. Sjoblom, S. Jones, L.D. Wood, et al., The consensus coding sequences of human breast and colorectal cancers, Science, 314(5797): 268-274, 2006.
17. F. Campagne and L. Skrabanek, Mining expressed sequence tags identifies cancer markers of clinical interest, BMC Bioinformatics, 7: 481, 2006.
18. C.H. Chung, P.S. Bernard, and C.M. Perou, Molecular portraits and the family tree of cancer, Nature Genetics, 32: 533-540.
19. E. Segal, N. Friedman, D. Koller, and A. Regev, A module map showing conditional activity of expression modules in cancer, Nature Genetics, 36(10): 1090-1098, 2004.
20. J.B. Welsh, L.M. Sapinoso, S.G. Kern, et al., Large-scale delineation of secreted protein biomarkers overexpressed in cancer tissue and serum, PNAS, 100(6): 3410-3415, 2003.
21. J.E. Staunton, D.K. Slonim, H.A. Coller, et al., Chemosensitivity prediction by transcriptional profiling, PNAS, 98(19): 10787-10792, 2001.
22. S. Dan, T. Tsunoda, O. Kitahara, et al., An integrated database of chemosensitivity to 55 anticancer drugs and gene expression profiles of 39 human cancer cell lines, Cancer Res., 62(4), 1139-1147, 2002.
23. E.C. Gunther, D.J. Stone, R.W. Gerwien, et al., Prediction of clinical drug efficacy by classification of drug-induced genomic expression profiles in vitro, PNAS, 100(16): 9608-9613, 2003.
24. A. Potti, H.K. Dressman, A. Bild, et al., Genomic signatures to guide the use of chemotherapeutics, Nature Medicine, 12(11): 1294-1300, 2006.
25. A. Esquela-Kerscher and F.J. Slack, Oncomirs [-] microRNAs with a role in cancer, Nature Reviews Cancer, 6(4): 259-269, 2006.
26. J.P. Lambert, M. Ethier, J.C. Smith, and D. Figeys, Proteomics: from gel based to gel free, Anal. Chem., 77: 3771-3787, 2005.
27. K.S. Anderson and J. LaBaer, The sentinel within: Exploiting the immune system for cancer biomarkers. J. Proteome. Res., 4: 1123-1133, 2005.
28. E.F. Petricoin, A.M. Ardekani, B.A. Hitt, et al., Use of proteomic patterns in serum to identify ovarian cancer, Lancet, 359: 572-577, 2002.
29. E.P. Diamandis, Serum proteomic profiling by matrix-assisted laser desorptionionization time-of-flight mass spectrometry for cancer diagnosis: Next steps, Cancer Res., 66(11): 5540-5541, 2006.
30. T.M. Pawlik, D.H. Hawke, Y. Liu, et al., Proteomic analysis of nipple aspirate fluid from women with early-stage breast cancer using isotope-coded affinity tags and tandem mass spectrometry reveals differential expression of vitamin D binding protein, BMC Cancer, 6: 68, 2006.
31. G. Chen, T.G. Gharib, C. Huang, et al., Proteomic analysis of lung adenocarcinoma: Identification of a highly expressed set of proteins in tumors, Clin. Cancer Res., 8(7): 2298-2305, 2002.
32. A. Grolleau, J. Bowman, B. Pradet-Balade, et al., Global and specific translational control by rapamycin in T cells uncovered by microarrays and proteomics, J. Biol. Chem., 277(25): 22175-22184, 2002.
33. E.F. Petricoin, C. Belluco, R.P. Araujo, and L.A. Liotta, The blood peptidome: A higher dimension of information content for cancer biomarker discovery, Nat. Rev. Cancer, 6: 961-967, 2006.
34. E.F. Petricoin, III, V.E. Bichsel, V.S. Calvert, et al., Mapping molecular networks using proteomics: A vision for patient-tailored combination therapy, J. Clin. Oncol., 23(15): 3614-3621, 2005.
35. R.S. Tirumalai, K.C. Chan, D.A. Prieto, et al., Characterization of the low molecular weight human serum proteome, Mol. Cell. Proteomics, 2(10): 1096-1103, 2003.
36. M.S. Lowenthal, A.I. Mehta, K. Frogale, et al., Analysis of albumin-associated peptides and proteins from ovarian cancer patients, Clin. Chem., 51: 1933-1945, 2005.
37. J. Palacios, E. Honrado, A. Osorio, et al., Phenotypic characterization of BRCA1 and BRCA2 tumors based in a tissue microarray study with 37 immunohistochemical markers, Breast Cancer Res. Treat., 90(1): 5-14, 2005.
38. M. Uhlen, E. Bjorling, C. Agaton, et al., A human protein atlas for normal and cancer tissues based on antibody proteomics, Mol. Cell Proteomics, 4(12): 1920-1932, 2005.
39. J.E. Ippolito, J. Xu, S. Jain, et al., An integrated functional genomics and metabolomics approach for defining poor prognosis in human neuroendocrine cancers, PNAS, 102(28): 9901-9906, 2005.
40. B. Perroud, J. Lee, N. Valkova, et al., Pathway analysis of kidney cancer using proteomics and metabolic profiling, Mol. Cancer, 5: 64, 2006.
41. G.V. Glinsky, O. Berezovska, and A.B. Glinskii, Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer, J. Clin. Invest., 115(6): 1503-1521, 2005.
42. I.C. Gerling, S. Singh, N.I. Lenchik, et al., New data analysis and mining approaches identify unique proteome and transcriptome markers of susceptibility to autoimmune diabetes. Mol. Cell Proteomics, 5(2): 293-305, 2006.
43. A. Dalgleish and H. Pandha, Tumor antigens as surrogate markers and targets for therapy and vaccines, Adv. Cancer Res., 96: 175-190, 2007.
44. A.M. Jubb, H.I. Hurwitz, W. Bai, et al., Impact of vascular endothelial growth factor-A expression, thrombospondin-2 expression, and microvessel density on the treatment effect of bevacizumab in metastatic colorectal cancer, J. Clin. Oncol., 24(2): 217-227, 2006.
45. A. Sandler, R. Gray, M.C. Perry, et al., Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer, N. Engl. J. Med., 355(24): 2542-2550, 2006.
46. R.L. Wahl, Tositumomab and 131I therapy in non-hodgkin's lymphoma, J. Nucl. Med., 46(1 suppl): 128S-140, 2005.
47. G.L. Plosker and D.P. Figgitt, Rituximab: A review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia, Drugs, 63: 803-843, 2003.
48. S.A. Jacobs, N. Vidnovic, J. Joyce, et al. Full-dose 90Y ibritumomab tiuxetan therapy is safe in patients with prior myeloablative chemotherapy, Clin. Cancer Res., 11(19): 7146s-7150, 2005.
49. N.E. Hynes and H.A. Lane, Erbb Receptors and Cancer: The Complexity of Targeted Inhibitors, Nat. Rev. Cancer, 5(5): 341-354, 2005.
50. D.J. Slamon, B. Leyland-Jones, S. Shak, et al., Use of chemotherapy plus a monoclonal antibody against HER2 for Metastatic breast cancer that overexpresses HER2, N. Engl. J. Med., 344(11): 783-792, 2001.
51. F.J. Esteva, C.D. Cheli, H. Fritsche, et al., Clinical utility of serum HER2/neu in monitoring and prediction of progression-free survival in metastatic breast cancer patients treated with trastuzumab-based therapies, Breast Cancer Res., 7(4): R436-443, 2005.
52. T. Okegawa, M. Kinjo, K. Nutuhara, and E. Higashihara, Pretreatment serum level of HER2/nue as a prognostic factor in metastatic prostate cancer patients about to undergo endocrine therapy, International Journal of Urology, 13(9): 1197-1201, 2006.
53. A.M. Gonzalez-Angulo, G.N. Hortobagyi, and F.J. Esteva, Adjuvant therapy with trastuzumab for HER-2/neu-positive breast cancer, Oncologist, 11(8): 857-867, 2006.
54. Y. Nagata, K.H. Lan, X. Zhou, et al., PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients, Cancer Cell, 6(2): 117-127, 2004.
55. C. Kari, T.O. Chan, M. Rocha de Quadros, and U. Rodeck, targeting the epidermal growth factor receptor in cancer: Apoptosis takes center stage, Cancer Res., 63(1): 1-5, 2003.
56. W.S. Siegel-Lakhai, J.H. Beijnen, and J.H.M. Schellens, Current knowledge and future directions of the selective epidermal growth factor receptor inhibitors erlotinib (Tarceva(R)) and gefitinib (Iressa(R)), Oncologist, 10(8): 579-589, 2005.
57. L. Toschi and F. Cappuzzo, understanding the new genetics of responsiveness to epidermal growth factor receptor tyrosine kinase inhibitors, Oncologist, 12(2): 211-220, 2007.
58. A. Hirata, F. Hosoi, M. Miyagawa, et al., HER2 overexpression increases sensitivity to gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, through inhibition of HER2/HER3 heterodimer formation in lung cancer cells, Cancer Res., 65(10): 4253-4260, 2005.
59. C.A. Casiano, M. Mediavilla-Varela, and E.M. Tan, Tumor-associated antigen arrays for the serological diagnosis of cancer, Mol. Cell. Proteomics, 5(10): 1745-1759, 2006.
60. M.J. Scanlan, S. Welt, C.M. Gordon, et al., Cancer-related serological recognition of human colon cancer: Identification of potential diagnostic and immunotherapeutic targets, Cancer Res., 62(14): 4041-4047, 2002.
61. J. Cui, W. Li, J. Wang, et al., Proteomics-based identification of human acute leukemia antigens that induce humoral immune response, Mol. Cell Proteomics, 4(11): 1718-1724, 2005.
62. L. Zhong, S.P. Coe, A.J. Stromberg, et al., Profiling tumor-associated antibodies for early detection of non-small cell lung cancer, J. Thorac. Oncol., 1: 513-519, 2006.
63. X. Wang, J. Yu, A. Sreekumar, et al., Autoantibody signatures in prostate cancer, N. Engl. J. Med., 353(12): 1224-1235, 2005.
64. K.C. Garcia, M. Degano, L.R. Pease, et al., Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen, Science, 279(5354): 1166-1172, 98.
65. J.W. Yewdell, U. Schubert, and J.R. Bennink, At the crossroads of cell biology and immunology: DRiPs and other sources of peptide ligands for MHC class I molecules, J. Cell Sci., 114(5): 845-851, 2001.
66. T.M. Clay, A.C. Hobeika, P.J. Mosca, et al., Assays for monitoring cellular immune responses to active immunotherapy of cancer, Clin. Cancer Res., 7(5): 1127-1135, 2001.
67. V. Brusic, V.B. Bajic, and N. Petrovsky, Computational methods for prediction of T-cell epitopes-a framework for modelling, testing, and applications, Methods, 34: 436-443, 2004.
68. B. Trost, M. Bickis, and A. Kusalik, Strength in numbers: Achieving greater accuracy in MHC-I binding prediction by combining the results from multiple prediction tools, Immunome Res., 3: 5, 2007.
69. I.D. Davis, M. Jefford, P. Parente, and J. Cebon, Rational approaches to human cancer immunotherapy, J. Leukoc Biol., 73(1): 3-29, 2003.
70. S.M. Schmidt, K. Schag, M.R. Muller, et al., Survivin is a shared tumor-associated antigen expressed in a broad variety of malignancies and recognized by specific cytotoxic T cells, Blood, 102(2): 571-576, 2003.
71. Y. Oka, A. Tsuboi, T. Taguchi, et al., Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression, PNAS, 101(38): 13885-13890, 2004.
72. L. Chin, L.A. Garraway, and D.E. Fisher, Malignant melanoma: Genetics and therapeutics in the genomic era, Genes Dev., 20(16): 2149-2182, 2006.
73. B.K. Edwards, M.L. Brown, P.A. Wingo, et al., Annual report to the nation on the status of cancer, 1975-2002, featuring population-based trends in cancer treatment, J. Natl. Cancer Inst., 97(19): 1407-1427, 2005.
74. V. Winnepenninckx, V. Lazar, S. Michiels, et al., Gene expression profiling of primary cutaneous melanoma and clinical outcome, J. Natl. Cancer Inst., 98(7): 472-482, 2006.
75. M.D. Onken, L.A. Worley, J.P. Ehlers, and J.W. Harbour, Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death, Cancer Res., 64(20): 7205-7209, 2004.
76. K. Hoek, D.L. Rimm, K.R. Williams, et al., Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas, Cancer Res., 64: 5270-5282, 2004.
77. T. Talebi, and J.S. Weber, Peptide vaccine trials for melanoma: preclinical background and clinical results, Semin. Cancer Biol., 13: 431-438, 2003.
78. T. Di Pucchio, L. Pilla, I. Capone, et. al., Immunization of stage IV melanoma patients with melan-A/MART-1 and gp 100 peptides plus IFN-{alpha} results in the activation of specific CD8+ T cells and monocyte/dendritic cell precursors, Cancer Res., 66(9): 4943-4951, 2006.
79. C.P. Tarassoff, P.M. Arlen, and J.L. Gulley, Therapeutic vaccines for prostate cancer, Oncologist, 11(5): 451-462, 2006.
80. N. Meidenbauer, D.T. Harris, L.E. Spitler, and T.L. Whiteside, Generation of PSA-reactive effector cells after vaccination with a PSA-based vaccine in patients with prostate cancer, Prostate, 43: 88-100, 2000.
81. H.L. Kaufman, W. Wang, J. Manola, et al., Phase II randomized study of vaccine treatment of advanced prostate cancer (E7897): A trial of the Eastern Cooperative Oncology Group, J. Clin. Oncol., 22: 2122-2132, 2004.
82. M. Noguchi, K. Itoh, A. Yao, et al., Immunological evaluation of individualized peptide vaccination with a low dose of estramustine for HLA-A24+HRPC patients, Prostate, 63: 1-12, 2005.
83. V.J. Assikis, K.-A. Do, S. Wen, et al., Clinical and biomarker correlates of androgen-independent, locally aggressive prostate cancer with limited metastatic potential, Clin. Cancer Res., 10(20): 6770-6778, 2004.
84. P.M. Arlen, J.L. Gulley, C. Parker, et al., A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer, Clin. Cancer Res., 12(4): 1260-1269, 2006.
85. A.M. Lin, R.M. Hershberg, and E.J. Small, Immunotherapy for prostate cancer using prostatic acid phosphatase loaded antigen presenting cells, Urol. Oncol., 24: 434-41, 2006.
86. N.E. Hynes and H.A. Lane, ERBB Receptors and cancer: The complexity of targeted inhibitors, Nat. Rev. Cancer, 5(5): 341-354, 2005.
87. E. Quaglino, S. Rolla, M. Iezzi, et al., Concordant morphologic and gene expression data show that a vaccine halts HER-2/neu preneoplastic lesions, J. Clin. Invest., 113(5): 709-717, 2004.
88. E.A. Mittendorf, C.E. Storrer, C.D. Shriver, et al., Investigating the combination of trastuzumab and HER2/neu peptide vaccines for the treatment of breast cancer, Ann. Surg. Oncol., 13: 1085-1098, 2006.
89. A.J. Muller and P.A. Scherle, Targeting the mechanisms of tumoral immune tolerance with small-molecule inhibitors, Nature Review Cancer, 6(8): 613-625, 2006.
90. G.Q. Phan, J.C. Yang, R.M. Sherry, et al., Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma, PNAS, 100(14): 8372-8377, 2003.
91. G.J.D. Van Mierlo, Z.F.H.M. Boonman, H.M.H. Dumortier, et al., Activation of dendritic cells that cross-present tumor-derived antigen licenses CD8+ CTL to cause tumor eradication, J. Immunol., 173(11): 6753-6759, 2004.
92. I.D. Davis, M. Jefford, P. Parente, and J. Cebon, Rational approaches to human cancer immunotherapy, J. Leukoc. Biol., 73(1): 3-29, 2003.
93. J. Copier, M. Whelan, and A. Dalgleish, Biomarkers for the development of cancer vaccines: Current status, Mol. Diagn. Ther., 10: 337-343, 2006.
94. C. Lurquin, B. Lethe, E. De Plaen, et.al., Contrasting frequencies of antitumor and anti-vaccine T cells in metastases of a melanoma patient vaccinated with a MAGE tumor antigen, J. Exp. Med., 201(2): 249-257, 2005.
95. D.H. Munn and A.L. Mellor, The tumor-draining lymph node as an immuneprivileged site, Immunol. Rev., 213: 146-158, 2006.
96. S. Gutman and L.G. Kessler, The US Food and Drug Administration perspective on cancer biomarker development, Nature Review Cancer, 6(7): 565-571, 2006.
97. L. Jeu, F.J. Piacenti, A.G. Lyakhovetskiy, and H.B.V. Fung, Clin. Ther., 25: 1321-1381, 2003.
98. R. Roskoski, Jr., Structure and regulation of Kit protein-tyrosine kinase-the stem cell factor receptor, Biochem. Biophys. Res. Commun., 338: 1307-1315, 2005.
99. L.K. Mattison, J. Fourie, Y. Hirao, et al., The uracil breath test in the assessment of dihydropyrimidine dehydrogenase activity: Pharmacokinetic relationship between expired 13CO2 and plasma [2-13C]dihydrouracil, Clin. Cancer Res., 12(2): 549-555, 2006.
100. E.B. Elkin, M.C. Weinstein, E.P. Winer, et al., HER-2 Testing and trastuzumab therapy for metastatic breast cancer: A cost-effectiveness analysis, J. Clin. Oncol., 22(5): 854-863, 2004.
101. R.D. Mass, M.F. Press, S. Anderson, et al., Evaluation of clinical outcomes according to HER2 detection by fluorescence in situ hybridization in women with metastatic breast cancer treated with trastuzumab, Clin. Breast Cancer, 6: 240-246, 2005.
102. J.G. Paez, P.A. Janne, J.C Lee, et al., EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy, Science, 304(5676): 1497-1500, 2004.
103. S. Paik, S. Shak, G. Tang, et al., A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer, N. Engl. J. Med., 351(27): 2817-2826, 2004.
104. A.M. Glas, A. Floore, L.J. Delahaye, et al., Converting a breast cancer microarray signature into a high-throughput diagnostic test, BMC Genomics, 7: 278, 2006.
105. C.L. Vogel, M.A. Cobleigh, D. Tripathy, et al., Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer, J. Clin. Oncol., 20(3): 719-726, 2002.
106. D.J. Slamon, B. Leyland-Jones, S. Shak, et al., Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2, N. Engl. J. Med., 344(11): 783-792, 2001.