Tumour markers and FDG PET/CT for prediction of disease relapse in patients with breast cancer

  • Laura Evangelista
  • Zora Baretta
  • Lorenzo Vinante
  • Anna Rita Cervino
  • Michele Gregianin
  • Cristina Ghiotto
  • Giorgio Saladini
  • Guido Sotti
Original Article



The aim of the study was to assess the role of CA 15.3, CT and positron emission tomography (PET)/CT in patients with breast cancer and suspected disease relapse after primary treatment.


We studied 111 consecutive patients (mean age 61 ± 12 years) with previous breast cancer, already treated and with clinical or biochemical suspicion of disease relapse. All patients underwent CT and 18F-fluorodeoxyglucose (FDG) PET/CT. In all patients, the value of CA 15.3 was compared to PET/CT and CT. The final diagnosis of relapse was established by invasive and noninvasive follow-up and was compared with CA 15.3, CT and PET/CT results. Univariate and multivariate analyses were used to identify the independent predictors of disease relapse and receiver-operating characteristic (ROC) curve for the identification of optimal CA 15.3 cutoff.


Of all patients, 40 (36%) showed an increased CA 15.3 value, CT was positive in 73 (66%), whereas at PET/CT imaging 64 (58%) showed positive findings for disease relapse. Of 40 patients with increased marker levels, 22 patients had positive CT and 30 positive PET/CT (55 vs 75%, p < 0.001). At the end of follow-up, recurrence occurred in 32 (29%) patients, 16 (50%) of whom showed high levels of CA 15.3. PET/CT predicted relapse in 26 (81%) patients, whereas CT correctly identified 23 (72%). At univariate analysis, recurrence was significantly associated with high CA 15.3 values (p < 0.05) and positive PET/CT (p < 0.005). At multivariable analysis only positive PET/CT remained an independent predictor of disease relapse (p < 0.05). ROC analysis showed an optimal cutoff point for CA 15.3 of 19.1 U/ml (AUC 0.65, p < 0.01) to individuate positive PET/CT.


FDG PET/CT is more sensitive than CT and CA 15.3 in the evaluation of disease relapse. PET/CT might be considered a complementary imaging technique during follow-up in patients with breast cancer.


Breast cancer Tumour markers Positron emission tomography Disease relapse Follow-up 


  1. 1.
    van Dongen JA, Voogd AC, Fentiman IS, Legrand C, Sylvester RJ, Tong D, et al. Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst 2000;92:1143–50.CrossRefPubMedGoogle Scholar
  2. 2.
    Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 2007;25:5287–312.CrossRefPubMedGoogle Scholar
  3. 3.
    Grassetto G, Fornasiero A, Otello D, Bonciarelli G, Rossi E, Nashimben O, Minicozzi AM, Crepaldi G, Pasini F, Facci E, Mandoliti G, Marzola MC, Al-Nahhas A, Rubello D. (18)F-FDG-PET/CT in patients with breast cancer and rising Ca 15-3 with negative conventional imaging: a multicentre study. Eur J Radiol 2010 May 21 [Epub ahead of print]Google Scholar
  4. 4.
    Siggelkow W, Rath W, Buell U, Zimny M. FDG PET and tumour markers in the diagnosis of recurrent and metastatic breast cancer. Eur J Nucl Med Mol Imaging 2004;31:S118–24.CrossRefPubMedGoogle Scholar
  5. 5.
    Liu CS, Shen YY, Lin CC, Yen RF, Kao CH. Clinical impact of [(18)F]FDG-PET in patients with suspected recurrent breast cancer based on asymptomatically elevated tumor marker serum levels: a preliminary report. Jpn J Clin Oncol 2002;32:244–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Suárez M, Pérez-Castejón MJ, Jiménez A, Domper M, Ruiz G, Montz R, et al. Early diagnosis of recurrent breast cancer with FDG-PET in patients with progressive elevation of serum tumor markers. Q J Nucl Med 2002;46:113–21.PubMedGoogle Scholar
  7. 7.
    Flamen P, Hoekstra OS, Homans F, Van Custem E, Maes A, Stroobants S, et al. Unexplained rising carcinoembryonic antigen (CEA) in the postoperative surveillance of colorectal cancer: the utility of positron emission tomography (PET). Eur J Cancer 2001;37:862–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Zangheri B, Messa C, Picchio M, Gianolli L, Landoni C, Fazio F. PET/CT and breast cancer. Eur J Nucl Med Mol Imaging 2004;31:S135–42.CrossRefPubMedGoogle Scholar
  9. 9.
    Strauss LG, Conti PS. The application of PET in clinical oncology. J Nucl Med 1991;32:623–48.PubMedGoogle Scholar
  10. 10.
    Brown RS, Leung JY, Fisher SJ, Frey KA, Ethier SP, Wahl RL. Intratumoral distribution of tritiated-FDG in breast carcinoma: correlation between Glut-1 expression and FDG uptake. J Nucl Med 1996;37:1042–47.PubMedGoogle Scholar
  11. 11.
    Haug AR, Schmidt GP, Klingenstein A, Heinemann V, Stieber P, Priebe M, et al. F-18-Fluoro-2-deoxyglucose positron emission tomography/computed tomography in the follow-up of breast cancer with elevated levels of tumor markers. J Comput Assist Tomogr 2007;31:629–34.CrossRefPubMedGoogle Scholar
  12. 12.
    Kamel EM, Wyss MT, Fehr MK, von Schulthess GK, Goerres GW. [18F]-Fluorodeoxyglucose positron emission tomography in patients with suspected recurrence of breast cancer. J Cancer Res Clin Oncol 2003;129:147–53.PubMedGoogle Scholar
  13. 13.
    The GIVIO Investigators. Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomized controlled trial. JAMA 1994;271:1587–92.CrossRefGoogle Scholar
  14. 14.
    Diel IJ, Solomayer EF, Costa SD, Gollan C, Goerner R, Wallwiener D, et al. Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med 1998;339:357–63.CrossRefPubMedGoogle Scholar
  15. 15.
    Buck A, Schirrmeister H, Kühn T, Shen C, Kalker T, Kotzerke J, et al. FDG uptake in breast cancer: correlation with biological and clinical prognostic parameters. Eur J Nucl Med Mol Imaging 2002;29:1317–23.CrossRefPubMedGoogle Scholar
  16. 16.
    Eubank WB, Mankoff DA, Vesselle HJ, Eary JF, Schubert EK, Dunnwald LK, et al. Detection of locoregional and distant recurrences in breast cancer patients by using FDG PET. Radiographics 2002;22:5–17.CrossRefPubMedGoogle Scholar
  17. 17.
    Eubank WB, Mankoff DA, Takasugi J, Vesselle H, Eary JF, Shanley TJ, et al. 18Fluorodeoxyglucose positron emission tomography to detect mediastinal or internal mammary metastases in breast cancer. J Clin Oncol 2001;19:3516–23.PubMedGoogle Scholar
  18. 18.
    Hathaway PB, Mankoff DA, Maravilla KR, Austin-Seymour MM, Ellis GK, Gralow JR, et al. Value of combined FDG PET and MR imaging in the evaluation of suspected recurrent local-regional breast cancer: preliminary experience. Radiology 1999;210:807–14.PubMedGoogle Scholar
  19. 19.
    Moon DH, Maddahi J, Silverman DH, Glaspy JA, Phelps ME, Hoh CK. Accuracy of whole-body fluorine-18-FDG PET for the detection of recurrent or metastatic breast carcinoma. J Nucl Med 1998;39:431–5.PubMedGoogle Scholar
  20. 20.
    Bender H, Kirst J, Palmedo H, Schomburg A, Wagner U, Ruhlmann J, et al. Value of 18fluoro-deoxyglucose positron emission tomography in the staging of recurrent breast carcinoma. Anticancer Res 1997;17:1687–92.PubMedGoogle Scholar
  21. 21.
    Lonneux M, Borbath II, Berlière M, Kirkove C, Pauwels S. The place of whole-body PET FDG for the diagnosis of distant recurrence of breast cancer. Clin Positron Imaging 2000;3:45–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Minn H, Soini I. [18F]Fluorodeoxyglucose scintigraphy in diagnosis and follow up of treatment in advanced breast cancer. Eur J Nucl Med 1989;15:61–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Yap CS, Seltzer MA, Schiepers C, Gambhir SS, Rao J, Phelps ME, et al. Impact of whole-body 18F-FDG PET on staging and managing patients with breast cancer: the referring physician’s perspective. J Nucl Med 2001;42:1334–7.PubMedGoogle Scholar
  24. 24.
    Grunfeld E, Mant D, Yudkin P, Adewuyi-Dalton R, Cole D, Stewart J, et al. Routine follow up of breast cancer in primary care: randomised trial. BMJ 1996;13:665–9.Google Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Laura Evangelista
    • 1
    • 2
  • Zora Baretta
    • 3
  • Lorenzo Vinante
    • 1
  • Anna Rita Cervino
    • 1
  • Michele Gregianin
    • 1
  • Cristina Ghiotto
    • 3
  • Giorgio Saladini
    • 1
  • Guido Sotti
    • 1
  1. 1.Radiotherapy and Nuclear Medicine UnitIstituto Oncologico Veneto IOV - IRCCSPadovaItaly
  2. 2.Departments of Biomorphological and Functional ImagingUniversity of Naples “Federico II”NaplesItaly
  3. 3.Oncology UnitIstituto Oncologico Veneto IOV - IRCCSPadovaItaly

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