Seminars in Oncology
Volume 29, Issue 3 , Pages 231-245 , June 2002

c-erbB-2 in breast cancer: Development of a clinically useful marker

References 

  1. Hayes DF, Bast R, Desch CE, et al.  A tumor marker utility grading system (TMUGS): A framework to evaluate clinical utility of tumor markers. J Natl Cancer Inst. 1996;88:1456–1466
  2. Hayes DF, Trock B, Harris A. Assessing the clinical impact of prognostic factors: When is “statistically significant” clinically useful?. Breast Cancer Res Treat. 1998;52:305–319
  3. Hayes DF. Do we need prognostic factors in nodal-negative breast cancer? Arbiter. Eur J Cancer. 2000;36:302–306
  4. Ellis M, Hayes DF, Lippman ME. Treatment of metastatic disease. In: ed 2.  Harris J,  Lippman M,  Morrow M, et al. editor. Diseases of the Breast. Philadelphia, PA,: Lippincott-Raven; 2000;p. 749–798
  5. Early Breast Cancer Trialist's Collaborative Group . Tamoxifen for early breast cancer: An overview of the randomized trials. Lancet. 1998;351:1451–1467
  6. Early Breast Cancer Trialist's Collaborative Group . Polychemotherapy for early breast cancer: An overview of the randomized trials. Lancet. 1998;352:930–942
  7. Early Breast Cancer Trialists Collaborative Group . Ovarian ablation in early breast cancer: Overview of the randomized trials. Lancet. 1996;348:1189–1196
  8. American Joint Committee on Cancer . Breast. In: ed 5.  Fleming I,  Cooper J,  Henson D, et al. editor. AJCC Cancer Staging Manual. Philadelphia: Lippincott-Raven; 1997;p. 171–180
  9. Hayes DF, Isaacs C, Stearns V. Prognostic factors in breast cancer: Current and new predictors of recurrence. J Mammary Gland Biol Neoplasia. 2001;6:375–392
  10. ASCO Expert Panel . Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer: Report of the American Society of Clinical Oncology Expert Panel. J Clin Oncol. 1996;14:2843–2877
  11. ASCO Expert Panel . 1997 update of recommendations for the use of tumor markers in breast and colorectal cancer. J Clin Oncol. 1998;16:793–795
  12. Bast RC, Ravdin P, Hayes DF, et al.  2000 Update of recommendations for the use of tumor markers in breast and colorectal cancer: Clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19:1865–1878
  13. Fitzgibbons PL, Page DL, Weaver D, et al.  Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000;124:966–978
  14. Tzahar E, Yarden Y. The ErbB-2/HER2 oncogenic receptor of adenocarcinomas: From orphanhood to multiple stromal ligands. Biochim Biophys Acta. 1998;1377:M25–M37
  15. Dickson RB, Lippman M. Oncogenes, suppressor genes, and signal transduction. In: ed 2.  Harris J,  Lippman M,  Morrow M, et al. editor. Diseases of the Breast. Philadelphia, PA,: Lippincott; 2000;p. 281–302
  16. Yarden Y, Sliwkowski MX. Untangling the ErbB signaling network. Nat Rev Mol Cell Biol. 2001;2:127–137
  17. Stark A, Hulka BS, Joens S, et al.  HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer. J Clin Oncol. 2000;18:267–274
  18. Xie D, Shu XO, Deng Z, et al.  Population-based, case-control study of HER2 genetic polymorphism and breast cancer risk. J Natl Cancer Inst. 2000;92:412–417
  19. King C, Kraus M, Aaronson S. Amplification of a novel v-erbB-2 related gene in human mammary carcinoma. Science. 1985;229:974–976
  20. Slamon DJ, Clark GM, Wong SG, et al.  Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177–182
  21. Slamon D, Godolphin W, Jones L, et al.  Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244:707–712
  22. Pietras R, Arboleda J, Reese D, et al.  HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells. Oncogene. 1995;10:2435–2446
  23. Hynes NE. Tyrosine kinase signaling in breast cancer. Breast Cancer Res. 2000;2:154–157
  24. 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;14:737–744
  25. Cobleigh MA, Vogel CL, Tripathy D, et al.  Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol. 1999;17:2639–2648
  26. 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;344:783–792
  27. Yamauchi H, Stearns V, Hayes DF. When is a tumor marker ready for prime time? A case study of c-erbB-2 as a predictive factor in breast cancer. J Clin Oncol. 2001;19:2334–2356
  28. Allred DC, Swanson PE. Testing for erbB-2 by immunohistochemistry in breast cancer. Am J Clin Pathol. 2000;113:171–175
  29. DiGiovanna MP, Stern DF. Activation state-specific monoclonal antibody detects tyrosine phosphorylated p185neu/erbB-2 in a subset of human breast tumors overexpressing this receptor. Cancer Res. 1995;55:1946–1955
  30. Thor AD, Liu S, Edgerton S, et al.  Activation (tyrosine phosphorylation) of ErbB-2 (HER-2/neu): A study of incidence and correlation with outcome in breast cancer. J Clin Oncol. 2000;18:3230–3239
  31. Simon R, Nocito A, Hubscher T, et al.  Patterns of her-2/neu amplification and overexpression in primary and metastatic breast cancer. J Natl Cancer Inst. 2001;93:1141–1146
  32. Thor A. Are patterns of HER-2/neu amplification and expression among primary tumors and regional metastases indicative of those in distant metastases and predictive of Herceptin response?. J Natl Cancer Inst. 2001;93:1120–1121
  33. Symmans WF, Liu J, Knowles DM, et al.  Breast cancer heterogeneity: Evaluation of clonality in primary and metastatic lesions. Hum Pathol. 1995;26:210–216
  34. Tanner M, Gancberg D, Di Leo A, et al.  Chromogenic in situ hybridization: A practical alternative for fluorescence in situ hybridization to detect HER-2/neu oncogene amplification in archival breast cancer samples. Am J Pathol. 2000;157:1467–1472
  35. Kallioniemi OP, Kallioniemi A, Kurisu W, et al.  ERBB2 amplification in breast cancer analyzed by fluorescence in situ hybridization. Proc Natl Acad Sci USA. 1992;89:5321–5325
  36. Press MF, Bernstein L, Thomas PA, et al.  HER-2/neu gene amplification characterized by fluorescence in situ hybridization: Poor prognosis in node-negative breast carcinomas. J Clin Oncol. 1997;15:2894–2904
  37. Jacobs T, Gown A, Yaziji H, et al.  Comparison of fluorescence in situ hybridization and immunohistochemistry for the evaluation of HER-2/neu in breast cancer. J Clin Oncol. 1999;17:1974–1982
  38. Wang S, Saboorian MH, Frenkel E, et al.  Laboratory assessment of the status of Her-2/neu protein and oncogene in breast cancer specimens: Comparison of immunohistochemistry assay with fluorescence in situ hybridization assays. J Clin Pathol. 2000;53:374–381
  39. Fabian CJ, Kimler BF, Zalles CM, et al.  Short-term breast cancer prediction by random periareolar fine-needle aspiration cytology and the Gail risk model. J Natl Cancer Inst. 2000;92:1217–1227
  40. Ravdin PM, Siminoff LA, Davis GJ, et al.  Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol. 2001;19:980–991
  41. Coates AS, Simes RJ. Patient Assessment of Adjuvant Treatment in Operable Breast Cancer. New York: NY, Wiley; 1992;
  42. Lindley C, Vasa S, Sawyer T, et al.  Quality of life and preferences for treatment following systemic adjuvant therapy for early stage breast cancer. J Clin Oncol. 1998;16:1380–1387
  43. Ravdin PM. Should HER2 status be routinely measured for all breast cancer patients?. Semin Oncol. 1999;26:117–123
  44. Trock BJ, Yamauchi H, Brotzman M, et al.  c-erbB-2 as a prognostic factor in breast cancer: A meta-analysis. Proc Am Soc Clin Oncol. 2000;19:97a; (abstr)
  45. Eppenberger-Castori S, Kueng W, Benz C, et al.  Prognostic and predictive significance of ErbB-2 breast tumor levels measured by enzyme immunoassay. J Clin Oncol. 2001;19:645–656
  46. Braun S, Schlimok G, Heumos I, et al.  ErbB2 overexpression on occult metastatic cells in bone marrow predicts poor clinical outcome of stage I-III breast cancer patients. Cancer Res. 2001;61:1890–1895
  47. Benz CC, Scott GK, Sarup JC, et al.  Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res Treat. 1992;24:85–95
  48. Carlomagno C, Perrone F, Gallo C, et al.  c-erbB2 overexpression decreases the benefit of adjuvant tamoxifen in early-stage breast cancer without axillary lymph node metastases. J Clin Oncol. 1996;14:2702–2708
  49. Bianco AR, De Laurentiis M, Carlomagno C, et al.  20 Years update of the Naples GUN Trial of adjuvant breast cancer therapy: Evidence of interaction between c-erbB-2 expression and tamoxifen efficacy. Proc Am Soc Clin Oncol. 1998;17:97a; (abstr)
  50. Bianco AR, De laurentiis M, Carlomagno C, et al.  HER2 overexpression predicts adjuvant tamoxifen failure for early breast cancer: Complete data at 20 year of the Naples GUN randomized trial. Proc Am Soc Clin Oncol. 2000;19:75a; (abstr)
  51. Berry DA, Muss HB, Thor AD, et al.  HER-2/neu and p53 expression versus tamoxifen resistance in estrogen receptor-positive, node-positive breast cancer. J Clin Oncol. 2000;18:3471–3479
  52. Wright C, Nicholson S, Angus B, et al.  Relationship between c-erbB-2 protein product expression and response to endocrine therapy in advanced breast cancer. Br J Cancer. 1992;65:118–121
  53. Leitzel K, Teramoto Y, Konrad K, et al.  Elevated serum c-erbB-2 antigen levels and decreased response to hormone therapy of breast cancer. J Clin Oncol. 1995;13:1129–1135
  54. Yamauchi H, O'Neill A, Gelman R, et al.  Prediction of response to antiestrogen therapy in advanced breast cancer patients by pretreatment circulating levels of extracellular domain of the HER-2/c-neu protein. J Clin Oncol. 1997;15:2518–2525
  55. Elledge RM, Green S, Ciocca D, et al.  HER-2 expression and response to tamoxifen in estrogen receptor-positive breast cancer: A Southwest Oncology Group study. Clin Cancer Res. 1998;4:7–12
  56. Houston SJ, Plunkett TA, Barnes DM, et al.  Overexpression of c-erbB2 is an independent marker of resistance to endocrine therapy in advanced breast cancer. Br J Cancer. 1999;79:1220–1226
  57. Berns EMJJ, Foekens JA, van Staveren IL, et al.  Oncogene amplification and prognosis in breast cancer: Relationship with systemic treatment. Gene. 1995;159:11–18
  58. Klijn J. Cell biological factors associated with the response of breast cancer to systemic treatment. Cancer Treat Rev. 1993;19SB:45–63
  59. Fehm T, Maimonis P, Katalinic A, et al.  The prognostic significance of c-erbB-2 serum protein in metastatic breast cancer. Oncology. 1998;55:33–38
  60. Archer SG, Eliopoulos A, Spandidos D, et al.  Expression of ras p21, p53 and c-erbB-2 in advanced breast cancer and response to first line hormonal therapy. Br J Cancer. 1995;72:1259–1266
  61. Nicholson RI, McClelland RA, Finlay P, et al.  Relationship between EGF-R, c-erbB-2 protein expression and Ki67 immunostaining in breast cancer and hormone sensitivity. Eur J Cancer. 1993;7:1018–1023
  62. Lipton A, Ali SM, Leitzel K, et al.  Elevated serum HER-2/neu level predicts decreased response to hormone therapy in metastatic breast cancer. Proc Am Soc Clin Oncol. 2000;19:71a; (abstr)
  63. Willsher PC, Beaver J, Pinder S, et al.  Prognostic significance of serum c-erbB-2 protein in breast cancer patients. Breast Cancer Res Treat. 1996;40:251–255
  64. Ellis MJ, Coop A, Singh B, et al.  Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: Evidence from a phase III randomized trial. J Clin Oncol. 2001;19:3808–3816
  65. Gusterson BA, Gelber RD, Goldhirsch A, et al.  Prognostic importance of c-erbB-2 expression in breast cancer. J Clin Oncol. 1992;10:1049–1056
  66. Allred DC, Clark G, Tandon A, et al.  HER-2/neu in node-negative breast cancer: Prognostic significance of overexpression influenced by the presence of in situ carcinoma. J Clin Oncol. 1992;10:599–605
  67. Miles DW, Harris WH, Gillett CE, et al.  Effect of c-erbB(2) and estrogen receptor status on survival of women with primary breast cancer treated with adjuvant cyclophosphamide/methotrexate/fluorouracil. Int J Cancer. 1999;84:354–359
  68. Menard S, Valagussa P, Pilotti S, et al.  Response to cyclophosphamide, methotrexate, and fluorouracil in lymph node-positive breast cancer according to HER2 overexpression and other tumor biologic variables. J Clin Oncol. 2001;19:329–335
  69. Stal O, Sullivan S, Wingren S, et al.  c-erbB-2 expression and benefit from adjuvant chemotherapy and radiotherapy of breast cancer. Eur J Cancer. 1995;31A:2185–2190
  70. Giai M, Roagna R, Ponzone R, et al.  Prognostic and predictive relevance of c-erbB-2 and ras expression in node positive and negative breast cancer. Anticancer Res. 1994;14:1441–1450
  71. Mehta R, McDermott J, Hieken T, et al.  Plasma c-erbB-2 levels in breast cancer patients: Prognostic significance in predicting response to chemotherapy. J Clin Oncol. 1998;16:2409–2416
  72. Anbazhagan R, Gelber RD, Bettelheim R, et al.  Association of c-erbB-2 expression and S-phase fraction in the prognosis of node positive breast cancer. Ann Oncol. 1991;2:47–53
  73. Wiltschke C, Kindas-Muegge I, Steininger A, et al.  Coexpression of HER-2/neu and p53 is associated with a shorter disease-free survival in node-positive breast cancer patients. J Cancer Res Clin Oncol. 1994;120:737–742
  74. van Diest PJ, Baak JP, Matze-Cok P, et al.  Prediction of response to adjuvant chemotherapy in premenopausal lymph node positive breast cancer patients with morphometry, DNA flow cytometry and HER-2/neu oncoprotein expression. Preliminary results. Pathol Res Pract. 1992;188:344–349
  75. Tetu B, Brisson J. Prognostic significance of HER-2/neu oncoprotein expression in node-positive breast cancer. The influence of the pattern of immunostaining and adjuvant therapy. Cancer. 1994;73:2359–2365
  76. Muss HB, Thor A, Berry DA, et al.  c-erbB-2 expression and S-phase activity predict response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med. 1994;330:1260–1266
  77. Thor A, Berry D, Budman D, et al.  erbB2, p53, and adjuvant therapy interactions in node positive breast cancer. J Natl Cancer Inst. 1998;90:1346–1360
  78. Petit T, Borel C, Ghnassia JP, et al.  Chemotherapy response of breast cancer depends on HER-2 status and anthracycline dose intensity in the neoadjuvant setting. Clin Cancer Res. 2001;7:1577–1581
  79. Paik S, Bryant J, Park C, et al.  erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. J Natl Cancer Inst. 1998;90:1361–1370
  80. Paik S, Bryant J, Tan-Chiu E, et al.  HER2 and choice of adjuvant chemotherapy for invasive breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-15. J Natl Cancer Inst. 2000;92:1991–1998
  81. Ravdin P, Green S, Albain K, et al.  Initial report of the SWOG biological correlative study of c-erbB-2 expression as a predictor of outcome in a trial comparing adjuvant CAF T with tamoxifen alone. Proc Am Soc Clin Oncol. 1998;17:97a; (abstr)
  82. Clahsen PC, van de Velde CJ, Duval C, et al.  p53 protein accumulation and response to adjuvant chemotherapy in premenopausal women with node-negative early breast cancer. J Clin Oncol. 1998;16:470–479
  83. Vera R, Albanell J, Lirola J, et al.  HER2 overexpresssion as a predictor of survival in a trial comparing adjuvant FAC and CMF in breast cancer. Proc Am Soc Clin Oncol. 1999;18:71a; (abstr)
  84. Di Leo A, Larsimont D, Beauduin M, et al.  CMF or anthracycline-based adjuvant chemotherapy for node-positive breast cancer patients: 4 year results of a Belgian randomized clinical trial with predictive markers analysis. Proc Am Soc Clin Oncol. 1999;18:69a; (abstr)
  85. Colozza M, Gori S, Mosconi A, et al.  c-erbB-2 expression as a predictor of outcome in a randomized trial comparing adjuvant CMF vs. single agent epirubicin in stage I-II breast cancer patients. Proc Am Soc Clin Oncol. 1999;18:70a; (abstr)
  86. Petruzelka LB, Pribylova O, Vedralova J, et al.  c-erbB-2 overexpression and treatment outcome in a randomized trial comparing adjuvant CMF and AC in equitoxic regimen in breast cancer. Proc Am Soc Clin Oncol. 2000;19:136a; (abstr)
  87. Niskanen E, Blomqvist C, Franssila K, et al.  Predictive value of c-erbB-2, p53, cathepsin-D, and histology of the primary tumour in metastatic breast cancer. Br J Cancer. 1997;76:917–922
  88. Revillion F, Hebbar M, Bonneterre J, et al.  Plasma c-erbB2 concentrations in relation to chemotherapy in breast cancer patients. Eur J Cancer. 1996;32A:231–234
  89. Gimenez L, Alvarez A, Mickiewicz E, et al.  Impact of the overexpression of HER-2-neu gene and mutant P53 suppressive gene on response and disease free survival in patients with locally advanced breast cancer. Proc Am Soc Clin Oncol. 1999;18:629a; (abstr)
  90. Vargas-Roig LM, Gago FE, Tello O, et al.  c-erbB-2 (HER-2/neu) protein and drug resistance in breast cancer patients treated with induction chemotherapy. Int J Cancer. 1999;84:129–134
  91. Rozan S, Vincent-Salomon A, Zafrani B, et al.  No significant predictive value of c-erbB-2 or p53 expression regarding sensitivity to primary chemotherapy or radiotherapy in breast cancer. Int J Cancer. 1998;79:27–33
  92. Geisler S, Lonning PE, Aas T, et al.  Influence of TP53 gene alternations and HER-2 expression on the response to treatment with doxorubicin in locally advanced breast cancer. Cancer Res. 2001;61:2505–2512
  93. Struce K, Reiners E, Audretsh W, et al.  Prediction of response to neoadjuvant EC chemotherapy. Breast Cancer Res Treat. 1999;57:62a; (abstr)
  94. Volm MD, Herman Y, Symmans WF, et al.  Her2 status predicts response to preoperative paclitaxel in patients with breast cancer. Proc Am Soc Clin Oncol. 1999;18:104a; (abstr)
  95. Seidman A, Baselga J, Yao T-J, et al.  HER-2/neu over-expression and clinical taxane sensitivity: A multivariate analysis in patients with metastatic breast cancer. Proc Am Soc Clin Oncol. 1996;15:104a; (abstr)
  96. Stender M, Neuberg D, Wood W, et al.  Correlation of circulating c-erbB-2 extracellular domain (HER-2) with clinical outcome in patients with metastatic breast cancer. Proc Am Soc Clin Oncol. 1997;16:154a; (abstr)
  97. Sjostrom J, Collan J, von Boguslawski K, et al.  C-erbB-2 expression does not predict response to docetaxel or sequential methotrexate and 5-fluorouracil in advanced breast cancer. Eur J Cancer. 2002;38:535–542
  98. Gianni L, Capri G, Mezzelani A, et al.  HER-2/neu amplification and response to doxorubicin/paclitaxel (AT) in women with metastatic breast cancer. Proc Am Soc Clin Oncol. 1997;16:139a; (abstr)
  99. Colomer R, Llombart A, Lluch A, et al.  Biweekly paclitaxel and gemcitabine in advanced breast cancer. Phase II trial and predictive value of HER2 extracellular domain. Proc Am Soc Clin Oncol. 2000;19:97a; (abstr)
  100. Konecny G, Thomssen M, Pegram M, et al.  HEr-2/neu gene amplification and response to paclitaxel in patients with metastatic breast cancer. Proc Am Soc Clin Oncol. 2001;20:23a; (abstr)
  101. Vogel C, Cobleigh MA, Tripathy D, et al.  First-line, single-agent Herceptin (trastuzumab) in metastatic breast cancer: A preliminary report. Eur J Cancer. 2001;37(suppl 1):S25–S29
  102. Vogel C, Cobleigh M, Tripathy D, et al.  First-line, non-hormonal, treatment of women with HER2 overexpressing metastatic breast cancer with herceptin (trastuzumab, humanized anti-HER2 antibody). Proc Am Soc Clin Oncol. 2000;19:71a; (abstr)
  103. Mass RD, Sanders C, Charlene K, et al.  The concordance between the clinical trials assay (CTA) and fluorescence in situ hybridization (FISH) in the Herceptin pivotal trials. Proc Am Soc Clin Oncol. 2000;19:75a; (abstr)
  104. Mass RD, Press M, Anderson S, et al.  Improved survival benefit from trastuzumab in patients selected by fluorescence in situ hybridization (FISH). In: Proc Am Soc Clin Oncol. 20:2001;p. 22a; (abstr)
  105. Vogel C, Cobleigh M, Tripathy D, et al.  Superior outcomes with trastuzumab in fluorescence in situ hybridization (FISH)-selected patients. Proc Am Soc Clin Oncol. 2001;20:22a; (abstr)
  106. Pegram M, Lipton A, Hayes DF, et al.  Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol. 1998;16:2659–2671
  107. Wong WL, Bajamonde A, Nelson B, et al: Baseline serum HER2 levels in the pivotal herceptin breast cancer trials: A comparison of 2 ELISA methods. Proc Am Soc Clin Oncol 19:77a, 20000 (abstr)

 Supported by the Fashion Footwear Association of New York/Shoes on Sale (D.F.H.) and the Lloyd Rader Endowed Chair, University of Oklahoma College of Medicine (A.T.).

☆☆ Address reprint requests to Daniel F. Hayes, MD, CCGC 6312, 1500 E Medical Center Dr, Ann Arbor, MI 48104.

PII: S0093-7754(02)50179-2

doi: 10.1053/sonc.2002.32899

Seminars in Oncology
Volume 29, Issue 3 , Pages 231-245 , June 2002