Abstract
Retrospective analysis previously identified significant elevation of five tumour markers, carcinoembryonic antigen (CEA), ferritin, orosomucoid,C-reactive protein and erythrocyte sedimentation rate (ESR), in patients with systemic breast cancer and showed that changes in each of these markers individually correlated significantly with therapeutic response. In this study we have prospectively tested these findings. None of the five markers was significantly elevated in primary breast cancer compared to normal control or benign breast disease groups. They therefore appear to have no role either in screening or in the differential diagnosis of breast cancer. There was a significant elevation of all five markers in patients with systemic breast cancer (P <0.0001; analysis of variance) but sequential changes in CEA and ESR only correlated significantly with the UICC-assessed response. Prospective confirmation of the correlation between changes in serum CEA and ESR provides the basis for using these markers in the assessment of response to therapy in patients with systemic breast cancer.
Key words: Breast cancer, Tumour markers, Therapeutic response
References
- 1.Bezwoda W, Derman D, Bothwell T, McPhil P, Levin J, De Moor N. Significance of serum concentrations of carcinoembryonic antigen, ferritin and calcitonin in breast cancer. Cancer. 1981;48:1623–1628. doi: 10.1002/1097-0142(19811001)48:7<1623::aid-cncr2820480725>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
- 2.British Breast Group Assessment of response to treatment in advanced breast cancer. Lancet. 1974;ii:38–39. [PubMed] [Google Scholar]
- 3.Cantwell B, Duffy MJ, Fennelly JJ, Duffy G. Carcinoembryonic antigen assay as a guide to tumour bulk, response to therapy and prognosis in human breast cancer. Irish J Med Sci. 1980;149:469–474. doi: 10.1007/BF02939191. [DOI] [PubMed] [Google Scholar]
- 4.Carcinoembryonic antigen: its role as a marker in the management of cancer National Institutes of Health consensus statement. Br Med J. 1981;282:373–375. doi: 10.1136/bmj.282.6261.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Chu TM, Nemoto T. Evaluation of carcinoembryonic antigen in human mammary carcinoma. J Nat Cancer Inst. 1973;51:1119–1122. doi: 10.1093/jnci/51.4.1119. [DOI] [PubMed] [Google Scholar]
- 6.Coombes RC, Gazet J-C, Sloane JP, Powles TJ, Ford HT, Lawrence DJR, Neville AM. Biochemical markers in breast cancer. Lancet. 1977;ii:132–134. doi: 10.1016/s0140-6736(77)91719-6. [DOI] [PubMed] [Google Scholar]
- 7.Coombes RC, Powles TJ, Gazet J-C, Ford HT, Nash AG, Sloane JP, Hillyard CJ, Thomas P, Keyser JW, Marcus D, Zinberg N, Stimson WH, Neville AM. A biochemical approach to the staging of human breast cancer. Cancer. 1977;40:937–944. doi: 10.1002/1097-0142(197708)40:2<937::aid-cncr2820400252>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
- 8.Coombes RC, Powles TJ, Gazet JC, Ford HT, McKinna A, Abbott Z, Gehrke CW, Keyser J-W, Mitchell PEG, Patel S, Stimson WH, Worwood M, Jones M, Neville AM. Screening for metastases in breast cancer: an assessment of biochemical and physical methods. Cancer. 1981;48:310–315. doi: 10.1002/1097-0142(19810715)48:2<310::aid-cncr2820480216>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
- 9.Cove DH, Woods KL, Smith SCH, Burnett D, Leonard J, Grieve RJ, Howell A. Tumour markers in breast cancer. Br J Cancer. 1979;40:710–718. doi: 10.1038/bjc.1979.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Cowen DM, Searle F, Ward AM, Benson EA, Smiddy FG, Eaves G, Cooper EH. Multivariate biochemical indicators of breast cancer: an evaulation of their potential in routine practice. Eur J Cancer. 1978;14:885–893. doi: 10.1016/0014-2964(78)90105-6. [DOI] [PubMed] [Google Scholar]
- 11.De Jong-Bakker M, Hart AAM, Persijn J-P, Cleton FJ. Prognostic significance of CEA in breast cancer: a statistical study. Eur J Cancer Clin Oncol. 1981;17:1307–1313. doi: 10.1016/0014-2964(81)90013-x. [DOI] [PubMed] [Google Scholar]
- 12.Doyle PJ, Nicholson RI, Groome GV, Blamey RW. Carcinoembryonic antigen (CEA): its role as a tumour marker in breast cancer. Clin Oncol. 1981;7:53–58. [PubMed] [Google Scholar]
- 13.Falkson HC, Van der Watt JJ, Portugal MA, Pitout MJ, Falkson G. Carcinoembryonic antigen in patients with breast cancer: an adjunctive tool to monitor response and therapy. Cancer. 1978;42:1308–1313. doi: 10.1002/1097-0142(197809)42:3<1308::aid-cncr2820420341>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
- 14.Haagensen DE, Kister SJ, Vandevoorde JP, Gates JB, Smart EK, Hansen HJ, Wells SA. Evaluation of carcinoembryonic antigen as a plasma monitor for human breast carcinoma. Cancer. 1978;42:1512–1519. doi: 10.1002/1097-0142(197809)42:3+<1512::aid-cncr2820420824>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
- 15.Hayward JL, Carbone PP, Heuson JC, Kumaoka S, Segaloff A, Rubens RD. Assessment of response to therapy in advanced breast cancer: a project of the Programme on Clinical Oncology of the International Union against Cancer, Geneva, Switzerland. Cancer. 1977;39:1289–1294. doi: 10.1002/1097-0142(197703)39:3<1289::aid-cncr2820390340>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
- 16.Hogan-Ryan A, Fennelly JJ, Jones M, Cantwell B, Duffy MJ. Serum sialyic acid and CEA concentration in human breast cancer. Br J Cancer. 1980;41:587–592. doi: 10.1038/bjc.1980.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Hortobagyi GN, Libshitz HI, Seabold JE. Osseous metastases of breast cancer. Clinical, biochemical, radiographic and scintigraphic evaluation of response to therapy. Cancer. 1984;53:577–582. doi: 10.1002/1097-0142(19840201)53:3<577::aid-cncr2820530335>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
- 18.Howell A, MacIntosh J, Jones M, Redford J, Wagstaff J, Sellwood RA. The definition of the “no change” category in patients treated with endocrine therapy and chemotherapy for advanced carcinoma of the breast. Eur J Cancer Clin Oncol. 1988;24:1567–1572. doi: 10.1016/0277-5379(88)90046-6. [DOI] [PubMed] [Google Scholar]
- 19.Krieger G, Wander HE, Prangen M, Banolow G, Nagel GA. Metastatic breast cancer with constantly low CEA blood levels. J Cancer Res Clin Oncol. 1984;108:341–344. doi: 10.1007/BF00390469. [DOI] [PubMed] [Google Scholar]
- 20.Krieger G, Prangen M, Klar R, Kneba M, Bandow G, Nagel GA. Diagnostische Validität der CEA — Bestimmung beim metastasierten Mammakarzinom. Klin Wochenschr. 1986;64:701–707. doi: 10.1007/BF01712055. [DOI] [PubMed] [Google Scholar]
- 21.Lamoureux G, Mandeville R, Poisson R, Legault-Poisson S, Jolicoeur R. Biologic markers in breast cancer: a multiparametric study: 1. Increased serum protein levels. Cancer. 1982;49:502–512. doi: 10.1002/1097-0142(19820201)49:3<502::aid-cncr2820490318>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
- 22.Laurence DJR, Stevens U, Bettelheim R, Darcy D, Leese C, Turberville C, Alexander P, Johns EW, Neville AM. Role of plasma carcinoembryonic antigen in diagnosis of gastro-intestinal, mammary and bronchial carcinoma. Br Med. 1972;3:605–609. doi: 10.1136/bmj.3.5827.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Lee YN. Serial tests of carcinoembryonic antigen in patients with breast cancer. Am J Clin Oncol. 1983;6:287–293. doi: 10.1097/00000421-198306000-00006. [DOI] [PubMed] [Google Scholar]
- 24.Lokich JJ, Zamcheck N, Lowenstein M. Sequential carcinoembryonic antigen levels in the therapy of metastatic breast cancer. Ann Intern Med. 1978;89:902–906. doi: 10.7326/0003-4819-89-6-902. [DOI] [PubMed] [Google Scholar]
- 25.Marcus D, Zinberg N. Isolation of ferritin from human mammary and pancreatic carcinomas by means of antibody immuno-absorbents. Arch Biochem Biophys. 1974;162:493–501. doi: 10.1016/0003-9861(74)90209-4. [DOI] [PubMed] [Google Scholar]
- 26.Nemoto T, Constantine R, Chu TM. Human tissue polypeptide antigen in breast cancer. J National Cancer Inst. 1979;63:1347–1350. [PubMed] [Google Scholar]
- 27.Palazzo S, Liguori V, Molinari B. Is the carcinoembryonic antigen test a valid predictor of response to medical therapy in disseminated breast cancer? Tumori. 1986;72:515–518. doi: 10.1177/030089168607200512. [DOI] [PubMed] [Google Scholar]
- 28.Rimsten A, Adami HO, Wahren B, Nordin B. Carcinoembryonic antigen in serum of unselected breast cancer patients and of non-hospitalised controls. Br J Cancer. 1979;39:109–115. doi: 10.1038/bjc.1979.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Roberts JG, Keyser JW, Baum M. Serum alpha 1-acid glycoprotein as an index of dissemination in breast cancer. Br J Surg. 1975;62:816–819. doi: 10.1002/bjs.1800621017. [DOI] [PubMed] [Google Scholar]
- 30.Robertson JFR, Williams MR, Todd J, Nicholson RI, Morgan DAL, Blamey RW. Factors predicting the response of patients with advanced breast cancer to endocrine (Megace) therapy. Eur J Cancer Clin Oncol. 1988;25:469–475. doi: 10.1016/0277-5379(89)90259-9. [DOI] [PubMed] [Google Scholar]
- 31.SPSS Inc . SPSSX User's Guide. New York: MacGraw-Hill; 1986. [Google Scholar]
- 32.Staab HJ, Anderer FA, Schindler AE, Ahlemann LM, Zwirner M. Optimizing tumour markers in breast cancer: Monitoring, prognosis and therapy control. Cancer Detect Prev. 1985;8:35–45. [PubMed] [Google Scholar]
- 33.Steward AM, Nixon D, Zamcheck N, Aisenberg A. Carcinoembryonic antigen in breast cancer patients: serum levels and disease progress. Cancer. 1974;33:1246–1252. doi: 10.1002/1097-0142(197405)33:5<1246::aid-cncr2820330509>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
- 34.Tormey DC, Waalkes TP. Clinical correlation between CEA and breast cancer. Cancer. 1978;42:1507–1511. doi: 10.1002/1097-0142(197809)42:3+<1507::aid-cncr2820420823>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
- 35.Tormey DC, Waalkes TP, Snyder JJ, Simon RM. Biological markers in breast carcinoma. III. Clinical correlation with carcinoembryonic antigen. Cancer. 1977;39:2397–2404. doi: 10.1002/1097-0142(197706)39:6<2397::aid-cncr2820390614>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
- 36.Waalkes TP, Gehrke CW, Tormey DC, Woo KB, Kuo KC, Snyder J, Hansen H. Biologic markers in breast carcinoma: IV. Serum fucose-protein ratio. Comparisons with carcinoembryonic antigen and human chorio gonadotrophin. Cancer. 1978;41:1871–1882. doi: 10.1002/1097-0142(197805)41:5<1871::aid-cncr2820410531>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
- 37.Wahren B, Lidbrink E, Wallgren A, Eneroth P, Zajicek J. Carcinoembryonic antigen and other tumour markers in tissue and serum or plasma of patients with primary mammary carcinoma. Cancer. 1978;42:1870–1878. doi: 10.1002/1097-0142(197810)42:4<1870::aid-cncr2820420426>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
- 38.Wang DY, Bulbrook RD, Hayward JL, Henricks JC, Franchimont P. Relationship between plasma carcinoembryonic antigen and prognosis in women with breast cancer. Eur J Cancer. 1975;11:615–618. doi: 10.1016/0014-2964(75)90094-8. [DOI] [PubMed] [Google Scholar]
- 39.Wang DY, Knyba RE, Bulbrook RD, Millis RR, Hayward JL. Serum carcinoembryonic antigen in the diagnosis and prognosis of women with breast cancer. Eur J Cancer Clin Oncol. 1984;20:25–31. doi: 10.1016/0277-5379(84)90030-0. [DOI] [PubMed] [Google Scholar]
- 40.Weinstein PS, Skinner M, Sipe JD, Lokich JJ, Zamcheck N, Cohen AS. Acute phase proteins or tumour markers: The role of SAA, SAP, CRP and CEA as indicators of metastases in a broad spectrum of neoplastic diseases. Scand J Immunol. 1984;19:193–198. doi: 10.1111/j.1365-3083.1984.tb00919.x. [DOI] [PubMed] [Google Scholar]
- 41.Williams MR, Turkes A, Pearson D, Twining P, Griffiths K, Blamey RW. The use of serum carcinoembryonic antigen to assess therapeutic response in locally advanced and metastatic breast cancer: a prospective study with external review. Eur J Surg Oncol. 1988;14:417–422. [PubMed] [Google Scholar]
- 42.Williams MR, Turkes A, Pearson D, Griffiths K, Blamey RW. Serum ferritin as a marker of therapeutic response in stage III and IV breast cancer. Eur J Surg Oncol. 1990;16:22–27. [PubMed] [Google Scholar]
- 43.Williams MR, Pearson DP, Turkes A, et al. Prognostic factors and assessment of therapeutic response in advanced breast cancer. Br J Cancer. 1990;61:126–132. doi: 10.1038/bjc.1990.26. [DOI] [PMC free article] [PubMed] [Google Scholar]