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British Journal of Cancer logoLink to British Journal of Cancer
. 1996 Oct;74(7):1126–1131. doi: 10.1038/bjc.1996.501

Utility of C-erbB-2 in tissue and in serum in the early diagnosis of recurrence in breast cancer patients: comparison with carcinoembryonic antigen and CA 15.3.

R Molina 1, J Jo 1, G Zanón 1, X Filella 1, B Farrus 1, M Muñoz 1, M L Latre 1, J Pahisa 1, M Velasco 1, P Fernandez 1, J Estapé 1, A M Ballesta 1
PMCID: PMC2077122  PMID: 8855986

Abstract

To evaluate the utility of c-erbB-2, carcinoembryonic antigen (CEA) and CA 15.3 in the early diagnosis of recurrence, serial serum determinations of these antigens were performed in 200 patients (follow-up 1-4 years, mean 2.2 years) with primary breast cancer and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). Eighty-nine patients developed metastases during follow-up. C-erbB-2, CEA and CA 15.3 were elevated (> 20 U ml-1, > 10 ng ml-1 or > 60 U ml-1 respectively) before diagnosis in 28%, 30% and 47% of the 89 patients with recurrence, with a lead time of 4.5 +/- 2.4, 4.9 +/- 2.4 and 4.8 +/- 2.4 months respectively. Tumour marker sensitivity was clearly related to the site of recurrence, with the lowest sensitivity found in locoregional relapse and the highest in patients with liver metastases. When patients with locoregional recurrences were excluded, sensitivity improved: 31% (c-erbB-2), 33% (CEA) and 56% (CA 15.3), with 76% having at least one of the three tumour markers. C-erbB-2 sensitivity in early diagnosis was significantly higher in patients with c-erbB-2 overexpression in tissue (8/10, 80%) than in those without overexpression (1/30, 3.3%) (P = 0.0001). Likewise, higher levels of both, c-erbB-2 and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse and a higher lead time were found in PR+ patients (CA 15.3, P < 0.0001) or in PR- patients (c-erbB-2, P = 0.009). Specificity of the tumour markers was 100% for all three markers (111 NED patients). In conclusion, c-erbB-2 is a useful tool for early diagnosis of metastases, mainly in those patients with c-erbB-2 overexpression in tissue. Using all three markers simultaneously it is possible to increase the sensitivity in the early diagnosis of recurrence by 11.2%.

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Selected References

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  1. Ahlemann L. M., Staab H. J., Anderer F. A. Serial CEA determinations as an aid in postoperative therapy management of patients with early breast cancer. Biomedicine. 1980 Dec;32(4):194–199. [PubMed] [Google Scholar]
  2. Albuquerque K. V., Price M. R., Badley R. A., Jonrup I., Pearson D., Blamey R. W., Robertson J. F. Pre-treatment serum levels of tumour markers in metastatic breast cancer: a prospective assessment of their role in predicting response to therapy and survival. Eur J Surg Oncol. 1995 Oct;21(5):504–509. doi: 10.1016/s0748-7983(95)96935-7. [DOI] [PubMed] [Google Scholar]
  3. Allred D. C., Clark G. M., Molina R., Tandon A. K., Schnitt S. J., Gilchrist K. W., Osborne C. K., Tormey D. C., McGuire W. L. Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. Hum Pathol. 1992 Sep;23(9):974–979. doi: 10.1016/0046-8177(92)90257-4. [DOI] [PubMed] [Google Scholar]
  4. Cases A., Filella X., Molina R., Ballesta A. M., Lopez-Pedret J., Revert L. Tumor markers in chronic renal failure and hemodialysis patients. Nephron. 1991;57(2):183–186. doi: 10.1159/000186247. [DOI] [PubMed] [Google Scholar]
  5. Chatal J. F., Chupin F., Ricolleau G., Tellier J. L., le Mevel A., Fumoleau P., Godin O., le Mevel B. P. Use of serial carcinoembryonic antigen assays in detecting relapses in breast cancer involving high risk of metastasis. Eur J Cancer. 1981 Feb;17(2):233–238. doi: 10.1016/0014-2964(81)90041-4. [DOI] [PubMed] [Google Scholar]
  6. Colomer R., Ruibal A., Genollà J., Salvador L. Circulating CA 15-3 antigen levels in non-mammary malignancies. Br J Cancer. 1989 Feb;59(2):283–286. doi: 10.1038/bjc.1989.58. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Coombes R. C., Powles T. J., Gazet J. C., Ford H. T., McKinna A., Abbott M., Gehrke C. W., Keyser J. W., Mitchell P. E., Patel S. Screening for metastases in breast cancer: an assessment of biochemical and physical methods. Cancer. 1981 Jul 15;48(2):310–315. doi: 10.1002/1097-0142(19810715)48:2<310::aid-cncr2820480216>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  8. DeVita V. T., Jr The James Ewing lecture. The relationship between tumor mass and resistance to chemotherapy. Implications for surgical adjuvant treatment of cancer. Cancer. 1983 Apr 1;51(7):1209–1220. doi: 10.1002/1097-0142(19830401)51:7<1209::aid-cncr2820510707>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  9. Goldie J. H. Mathematical models of drug resistance and chemotherapy effects. Cancer Treat Res. 1989;48:13–26. doi: 10.1007/978-1-4613-1601-5_2. [DOI] [PubMed] [Google Scholar]
  10. Kufe D., Inghirami G., Abe M., Hayes D., Justi-Wheeler H., Schlom J. Differential reactivity of a novel monoclonal antibody (DF3) with human malignant versus benign breast tumors. Hybridoma. 1984 Fall;3(3):223–232. doi: 10.1089/hyb.1984.3.223. [DOI] [PubMed] [Google Scholar]
  11. McKenzie S. J., DeSombre K. A., Bast B. S., Hollis D. R., Whitaker R. S., Berchuck A., Boyer C. M., Bast R. C., Jr Serum levels of HER-2 neu (C-erbB-2) correlate with overexpression of p185neu in human ovarian cancer. Cancer. 1993 Jun 15;71(12):3942–3946. doi: 10.1002/1097-0142(19930615)71:12<3942::aid-cncr2820711224>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  12. Minton J. P., Hoehn J. L., Gerber D. M., Horsley J. S., Connolly D. P., Salwan F., Fletcher W. S., Cruz A. B., Jr, Gatchell F. G., Oviedo M. Results of a 400-patient carcinoembryonic antigen second-look colorectal cancer study. Cancer. 1985 Mar 15;55(6):1284–1290. doi: 10.1002/1097-0142(19850315)55:6<1284::aid-cncr2820550622>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  13. Molina R., Ciocca D. R., Tandon A. K., Allred D. C., Clark G. M., Chamness G. C., Gullick W. J., McGuire W. L. Expression of HER-2/neu oncoprotein in human breast cancer: a comparison of immunohistochemical and western blot techniques. Anticancer Res. 1992 Nov-Dec;12(6B):1965–1971. [PubMed] [Google Scholar]
  14. Molina R., Filella X., Mengual P., Prats M., Zanon G., Daniels M., Ballesta A. M. MCA in patients with breast cancer: correlation with CEA and CA15-3. Int J Biol Markers. 1990 Jan-Mar;5(1):14–21. [PubMed] [Google Scholar]
  15. Molina R., Zanón G., Filella X., Moreno F., Jo J., Daniels M., Latre M. L., Giménez N., Pahisa J., Velasco M. Use of serial carcinoembryonic antigen and CA 15.3 assays in detecting relapses in breast cancer patients. Breast Cancer Res Treat. 1995;36(1):41–48. doi: 10.1007/BF00690183. [DOI] [PubMed] [Google Scholar]
  16. Narita T., Funahashi H., Satoh Y., Takagi H. C-erbB-2 protein in the sera of breast cancer patients. Breast Cancer Res Treat. 1992;24(2):97–102. doi: 10.1007/BF01961242. [DOI] [PubMed] [Google Scholar]
  17. Pupa S. M., Ménard S., Morelli D., Pozzi B., De Palo G., Colnaghi M. I. The extracellular domain of the c-erbB-2 oncoprotein is released from tumor cells by proteolytic cleavage. Oncogene. 1993 Nov;8(11):2917–2923. [PubMed] [Google Scholar]
  18. Silvestrini R., Sanfilippo O., Tedesco G. Kinetics of human mammary carcinomas and their correlation with the cancer and the host characteristics. Cancer. 1974 Oct;34(4):1252–1258. doi: 10.1002/1097-0142(197410)34:4<1252::aid-cncr2820340435>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  19. Slamon D. J., Godolphin W., Jones L. A., Holt J. A., Wong S. G., Keith D. E., Levin W. J., Stuart S. G., Udove J., Ullrich A. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989 May 12;244(4905):707–712. doi: 10.1126/science.2470152. [DOI] [PubMed] [Google Scholar]
  20. Staab H. J., Ahlemann L. M., Koch H. L., Anderer F. A. Serial carcinoembryonic antigen (CEA) determinations in the management of patients with breast cancer. Oncodev Biol Med. 1980;1(3):151–160. [PubMed] [Google Scholar]
  21. Zabrecky J. R., Lam T., McKenzie S. J., Carney W. The extracellular domain of p185/neu is released from the surface of human breast carcinoma cells, SK-BR-3. J Biol Chem. 1991 Jan 25;266(3):1716–1720. [PubMed] [Google Scholar]
  22. van Dalen A. Tumour markers in breast cancer. Ann Chir Gynaecol. 1989;78(1):54–64. [PubMed] [Google Scholar]

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