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c-erbB-2 oncoprotein, CEA, and CA 15.3 in patients with breast cancer: prognostic value

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Abstract

The diagnostic value of a new tumor marker, c-erbB-2, was studied in the sera of 50 healthy subjects, 58 patients with benign breast diseases, and 413 patients with breast cancer (186 locoregional, 185 with advanced disease, and 42 with no evidence of disease). Using 15 U/ml as the cut-off, no healthy subjects or patients with benign diseases and only 2.4% of no evidence of disease patients had elevated serum levels. Abnormal c-erbB-2 levels were found in 29% (101/370) of the patients with breast carcinoma (locoregional 9%, metastases 45.4%). CEA (cut-off 5 U/ml) and CA 15.3 (cut-off 35 U/ml) sensitivity was 18% and 16% in patients with locoregional disease and 61% and 70% in those patients with advanced disease, respectively. A trend toward higher serum levels of all three tumor markers in patients with nodal involvement or greater tumor size was found, but was statistically significant only with CEA (p < 0.01). By contrast, c-erbB-2 was related to steroid receptors, in both locoregional and metastatic tumors. When the prognostic value of these markers was evaluated, patients with abnormally high presurgical CEA and c-erbB-2 had a worse prognosis than those patients with normal values, in both node-negative (p < 0.05 and p < 0.001, respectively) and node-positive patients (p < 0.556 and p < 0.001, respectively). By contrast, no relationship was found between CA 15.3 values and prognosis. Multivariate analysis showed that CEA and c-erbB-2 were also prognostic factors. The correlation between serum and tissue levels of c-erbB-2 was studied in the tumors of 161 patients. Significantly higher c-erbB-2 serum levels were found in patients with overexpression in tissue by immunohistochemistry, in both locoregional and advanced disease (p=0.0001). Serum concentrations in patients with advanced disease were related to the site of recurrence, with significantly higher values in patients with metastases (mainly in those with liver metastases) than in those with locoregional recurrence. In summary, c-erbB-2 serum levels seem to be a useful tumor marker in the prognosis of patients with breast cancer. Using all three tumor markers, sensitivity was 35% in patients with locoregional breast cancer and 88% in patients with recurrence.

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References

  1. Hilkens J, Kroezen V, Bonfrer JMG, Bruning PF, Hilgers J, van Eijkeren J: A radioimmunoassay for a new antigen (Mam-6) present in the sera of patients with metastasized carcinomas. In: Peeters H (ed) Protides of the Biological Fluids. Pergamon Press, Oxford, 1985, pp 651–653

    Google Scholar 

  2. Kufe D, Inghirami G, Abe M, Hayes D, Justi-Wheeler H, Schlom J: Differential reactivity of a novel monoclonal antibody (DF-3) with human malignant versus benign breast tumors. Hybridoma 3: 223–232, 1984

    Google Scholar 

  3. Stahli C, Takacs B, Miggiano V, Stachelin T, Carman H: Monoclonal antibodies against antigens on breast cancer cells. Experientia 41: 1377–1381, 1985

    Google Scholar 

  4. Colomer R, Ruibal A, Salvador L: Circulating tumor marker levels in advanced breast carcinoma correlate with the extent of metastatic disease. Cancer 64: 1674–1681, 1989

    Google Scholar 

  5. Molina R, Ballesta AM: Evaluation of several tumor markers (MCA, CA 15.3, BCM and CA 549) in tissue and serum of patients with breast cancer. In: Ceriani RL (ed) Breast Epithelial Antigens. Molecular Biology to Clinical Applications, Plenum Press, New York 1991, pp 161–168

    Google Scholar 

  6. Molina R, Zanon G, Filella X, Moreno F, Jo J, Daniels M, Latre ML, Gimenez N, Pahisa J, Velasco M, Ballesta AM: Use of serial carcinoembryonic antigen and CA 15.3 assays in detecting relapses in breast cancer patients. Breast Cancer Res Treat 36: 41–48, 1995

    Google Scholar 

  7. Coussens L, Yang-Feng TL, Liao YC et al.: Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with the neu oncogene. Science 230: 1130–1139, 1985

    Google Scholar 

  8. Molina R, Ciocca R, Tandon AK, Allred DC, Clark GC, Chamness GC, Gullick WJ, McGuire WL: Expression of HER-2/neu oncoprotein in human breast cancer. A comparison of immunohistochemical and western blot techniques. Anticancer Res 12: 1965–1972, 1992

    Google Scholar 

  9. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, Ress MF: Studies of the HER-2 neu proto-oncogene in human breast and ovarian cancer. Science 244: 707–712, 1989

    Google Scholar 

  10. Tandon AK, Clark GM, Chamness GC, Ullrich A, McGuire WL: HER-2/neu oncogene protein and prognosis in breast cancer. J Clin Oncol 7: 1120–1128, 1989

    Google Scholar 

  11. Allred DC, Clark GM, Molina R, Tandon AK, Schnitt SJ, Gilchrist KW, Osborne CK, Tormey DC, Abeloff MD, McGuire WI: Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. Human Pathol 23: 974–979, 1992

    Google Scholar 

  12. Berger MS, Locher GW, Saurer S et al.: Correlation of cerbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. Cancer Res 48: 1238–1243, 1988

    Google Scholar 

  13. Marx D, Schauer A, Reiche Ch et al.: c-erbB-2 expression in correlation to other biological parameters of breast cancer. J Cancer Res Clin Oncol 116: 15–20, 1990

    Google Scholar 

  14. Molina R, Filella X, Segui MA, Climent MA, Perez-Picañol E, Alonso C, Jo J, Ojeda B, Tandon AK, Ballesta AM: Oncogenic proteins and prognostic correlations in breast cancer. In vivo 7: 585–590, 1993

    Google Scholar 

  15. Allred DC, Clark GM, Tandon AK, Molina R, Tormey DC, Osborne CK, Gilchrist KW, Mansour EG, Abeloff MD, McGuire WL: HER-2/neu in node-negative breast cancer: Prognostic significance of overexpression influenced by the presence of in situ carcinoma. J Clin Oncol 4: 599–605, 1992

    Google Scholar 

  16. Zabrecky JR, Lam T, McKenzie SJ, Carney W: The extracellular domain of p185 neu is released from the surface of human breast carcinoma cell, SK-BR-3. J Biol Chem 266: 1716–1720, 1991

    Google Scholar 

  17. Pupa SM, Menard S, Morelli D, Pozzi B, De Palo G, Colnaghi MI: The extracellular domain of the c-erbB-2 oncoprotein is released from tumor cells by proteolytic cleavage. Oncogene 8: 2917–2923, 1993

    Google Scholar 

  18. McKenzie SJ, De Sombre KA, Bast BS, Hollis DR, Whitaker RS, Berchuck A, Boyer CM, Bast RC: Serum levels of HER-2/neu (C-erbB-2) correlate with overexpression of p184 neu in human ovarian cancer. Cancer 71: 3942–3946, 1993

    Google Scholar 

  19. Narita T, Funahashi H, Satoh Y, Takagi H: C-erbB-2 in the sera of breast cancer patients. Breast Cancer Res Treat 24: 97–102, 1992

    Google Scholar 

  20. International Union Against Cancer (UICC): TNM classification of malignant tumours. In: Hermanek P, Soben LH (eds) 4 ed Springer Verlag, Berlin, 1987

    Google Scholar 

  21. Molina R, Jo J, Filella X, Bruix J, Castells A, Hague M, Ballesta AM: Serum levels of c-erbB-2 (HER-2/neu) in patients with malignant and non-malignant diseases. Tumour Biology 18: 188–196, 1997

    Google Scholar 

  22. Zhou DJ, Ahauja H, Cline MJ: Proto-oncogene abnormalities in human breast cancer: c-erbB-2 amplification does not correlate with recurrence of disease. Oncogene 4: 105–108, 1989

    Google Scholar 

  23. Molina R, Filella X, Torres MD, Ballesta AM, Mengual P, Cases A, Balague A: SCC antigen measured in malignant and nonmalignant diseases. Clin Chem 36: 251–254, 1990

    Google Scholar 

  24. Molina R, Filella X, Bruix J, Mengual P, Bosch J, Calvet X, Jo J, Ballesta AM: Cancer antigen 125 in serum and ascitic fluid of patients with liver diseases. Clin Chem 37: 1379–1383, 1991

    Google Scholar 

  25. Cases A, Filella X, Molina R, Ballesta AM, Lopez-Revert J, Revert L: Tumor markers in chronic renal failure and hemodialysis patients. Nephron 37: 1379–1383, 1991

    Google Scholar 

  26. Ritts RE Jr, Del Villano BC, Go VLW, Heberman RB, Klug TL, Zurawski VR Jr: Initial clinical evaluation of an immunoradiometric assay for CA 19.9 using the NCI serum bank. Int J Cancer 33: 339–345, 1984

    Google Scholar 

  27. Leitzel K, Teramoto Y, Konrad K, Chinchilli VM, Volas G, Grossberg H, Harvey H, Demers L, Lipton A: Elevated serum c-erbB-2 antigen levels and decreased response to hormone therapy of breast cancer. J Clin Oncol 13: 1129–1135, 1995

    Google Scholar 

  28. Molina R, Jo J, Zanon G, Filella X, Farrus M, Muñoz M, Latre ML, Pahisa J, Velasco M, Fernandez P, Estapé J, Ballesta AM: Utility of c-erbB-2 in tissue and in serum in the early diagnosis of recurrence in breast cancer patients: comparisc with carcinoembryonic antigen and CA 15.3. Br J Cancer 74: 1126–1131, 1996

    Google Scholar 

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Authors and Affiliations

  1. Laboratory of Clinical Biochemistry, Hospital Clinic, Medical School, Barcelona, Spain

    Rafael Molina, Judith Jo, Xavier Filella, Carmen Escriche & Antonio M. Ballesta

  2. Department of Gynecology, Hospital Clinic, Medical School, Barcelona, Spain

    Gabriel Zanon & Jaume Pahisa

  3. Oncology Unit, Hospital Clinic, Medical School, Barcelona, Spain

    Montserrat Muñoz & Jordi Estape

  4. Radiotherapy Oncology, Hospital Clinic, Medical School, Barcelona, Spain

    Blanca Farrus

  5. Department of Surgery, Hospital Clinic, Medical School, Barcelona, Spain

    Maria Luz Latre

Authors
  1. Rafael Molina
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  2. Judith Jo
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  3. Xavier Filella
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  4. Gabriel Zanon
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  11. Antonio M. Ballesta
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Molina, R., Jo, J., Filella, X. et al. c-erbB-2 oncoprotein, CEA, and CA 15.3 in patients with breast cancer: prognostic value. Breast Cancer Res Treat 51, 109–119 (1998). https://doi.org/10.1023/A:1005734429304

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  • DOI: https://doi.org/10.1023/A:1005734429304

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