Skip to main content

Advertisement

Log in

Circulating tumor cells in breast cancer and its association with tumor clinicopathological characteristics: a meta-analysis

  • Review Article
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The aim of the study was to evaluate the association between tumor clinicopathological characteristics and circulating tumor cells (CTCs) in breast cancer. We searched PubMed, MEDLINE, BioMed, and EMbase databases for studies that assessed the association between tumor clinicopathological characteristics and CTCs in breast cancer. Studies obtained from search strategy were screened using pre-specified criteria, and necessary data were retrieved for meta-analysis. Fourteen studies with 2,336 patients were eligible for combined analysis. Presence of CTCs in peripheral blood (PB) was significantly associated with tumor size [OR 0.68, 95 % confidence interval (CI) (0.54, 0.87), n = 10, P = 0.002], tumor grade [OR 0.71, 95 % CI (0.55, 0.91), n = 8, P = 0.006], ER status [OR 0.72, 95 % CI (0.57, 0.91), n = 9, P = 0.007], and PR status [OR 0.78, 95 % CI (0.61, 0.98), n = 9, P = 0.04]. However, as to correlation between nodal status and CTCs presence in PB, no statistically significant difference was found [OR 0.83, 95 % CI (0.67, 1.03), n = 12, P = 0.10]. The CTCs’ presence in PB is correlated with tumor size, tumor grade, ER, and PR.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

Abbreviations

CTCs:

Circulating tumor cells

ER:

Estrogen receptor

hMAM:

Human mammaglobin

LSC:

Laser scanning cytometry

OS:

Overall survival

PFS:

Progression-free survival

PR:

Progesterone receptor

PB:

Peripheral blood

References

  1. Wulfing P, Borchard J, Buerger H, et al. HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res. 2006;12:1715–20.

    Article  PubMed  Google Scholar 

  2. Pierga JY, Bonneton C, Vincent-Salomon A, et al. Clinical significance of immunocytochemical detection of tumor cells using digital microscopy in peripheral blood and bone marrow of breast cancer patients. Clin Cancer Res. 2004;10:1392–400.

    Article  CAS  PubMed  Google Scholar 

  3. Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781–91.

    Article  CAS  PubMed  Google Scholar 

  4. Pantel K, Brakenhoff RH. Dissecting the metastatic cascade. Nat Rev Cancer. 2004;4(6):448–56.

    Article  CAS  PubMed  Google Scholar 

  5. Cohen SJ, Punt CJ, Iannotti N, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(19):3213–21.

    Article  PubMed  Google Scholar 

  6. Ring AE, Zabaglo L, Ormerod MG, et al. Detection of circulating epithelial cells in the blood of patients with breast cancer: comparison of three techniques. Br J Cancer. 2005;92(5):906–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Pantel K, Riethdorf S. Pathology: are circulating tumor cells predictive of overall survival? Nat Rev Clin Oncol. 2009;6(4):190–1.

    Article  PubMed  Google Scholar 

  8. Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer. 2008;8:329–40.

    Article  CAS  PubMed  Google Scholar 

  9. Criscitiello C, Sotiriou C, Ignatiadis M. Circulating tumor cells and emerging blood biomarkers in Breast Cancer. Curr Opin Oncol. 2010;22:552–8.

    Article  CAS  PubMed  Google Scholar 

  10. Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781–91.

    Article  CAS  PubMed  Google Scholar 

  11. Lang JE, Mosalpuria K, Cristofanilli M, et al. HER2 status predicts the presence of circulating tumor cells in patients with operable breast cancer. Breast Cancer Res Treat. 2009;113:501–7.

    Article  CAS  PubMed  Google Scholar 

  12. Tao M, Ma D, Li Y, Zhou C, et al. Clinical significance of circulating tumor cells in breast cancer patients. Breast Cancer Res Treat. 2011;129:247–54.

    Article  PubMed  Google Scholar 

  13. Biggers B, Knox S, Grant M, et al. Circulating tumor cells in patients undergoing surgery for primary breast cancer: preliminary results of a pilot study. Ann Surg Oncol. 2009;16:969–71.

    Article  PubMed  Google Scholar 

  14. Ferro P, Franceschin MC, Bacigalupo B, et al. Detection of circulating tumour cells in breast cancer patients using human mammaglobin RT-PCR:association with clinical prognostic factors. Anticancer Res. 2010;30:2377–82.

    CAS  PubMed  Google Scholar 

  15. Yan Y, Cheng JP, Di LJ, Song GH, Ren J. Detection and clinical value of epithelial cellular adhension molecule (EpCAM) mRNA positive circulating tumor cells in metastatic breast cancer. Beijing Da Xue Xue Bao. 2012;44(2):275–80.

    CAS  PubMed  Google Scholar 

  16. Molloy TJ, Bosma AJ, Baumbusch LO, et al. The prognostic significance of tumour cell detection in the peripheral blood versus the bone marrow in 733 early-stage breast cancer patients. Breast Cancer Res. 2011;13(3):R61.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Nadal R, Fernandez A, Sanchez-Rovira P, et al. Biomarkers characterization of circulating tumour cells in breast cancer patients. Breast Cancer Res. 2012;14(3):R71.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Molloy TJ, Devriese LA, Helgason HH, Bosma AJ, Hauptmann M, Voest EE, Schellens JHM, van’t Veer LJ. A multimarker QPCR-based platform for the detection of circulating tumour cells in patients with early-stage breast cancer. Br J Cancer. 2011;104:1913–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Heo CK, Hwang HM, Ruem AH, et al. Identification of a mimotope for circulating anti-cytokeratin 8/18 antibody and its usage for the diagnosis of breast cancer. Int J Oncol. 2013;42:65–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Hwang SB, Bae JW, Lee HY, Kim HY. Circulating tumor cells detected by RT-PCR for CK-20 before surgery indicate worse prognostic impact in triple-negative and HER2 subtype breast cancer. J Breast Cancer. 2012;15(1):34–42.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Giuliano M, Giordano A, Jackson S, et al. Circulating tumor cells as prognostic and predictive markers in metastatic breast cancer patients receiving first-line systemic treatment. Breast Cancer Res. 2011;13(3):R67.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Xenidis N, Vlachonikolis I, Mavroudis D, et al. Peripheral blood circulating cytokeratin-19 mRNA-positive cells after the completion of adjuvant chemotherapy in patients with operable breast cancer. Ann Oncol. 2003;14:849–55.

    Article  CAS  PubMed  Google Scholar 

  23. Xenidis N, Ignatiadis M, Apostolaki S, et al. Cytokeratin-19 mRNA-positive circulating tumor cells after adjuvant chemotherapy in patients with early breast cancer. J Clin Oncol. 2009;27:2177–84.

    Article  CAS  PubMed  Google Scholar 

  24. Ignatiadis M, Rothe F, Chaboteaux C, et al. HER2-positive circulating tumor cells in breast cancer. PLoS One. 2011;6(1):e15624.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Zhang L, Riethdorf S, Wu G, et al. Meta-analysis of the prognostic value of circulating tumor cells in breast cancer. Clin Cancer Res. 2012;18:5701–10.

    Article  PubMed  Google Scholar 

  26. Janni W, Vogl FD, Wiedswang G, et al. Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse: a European pooled analysis. Clin Cancer Res. 2011;17:2967–76.

    Article  PubMed  Google Scholar 

  27. Zhang L, Riethdorf S, Wu G, et al. Meta-analysis of the prognostic value of circulating tumor cells in breast cancer. Clin Cancer Res. 2012;18(20):5701–10.

    Article  PubMed  Google Scholar 

  28. Allard WJ, Matera J, Miller MC, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004;10:6897–904.

    Article  PubMed  Google Scholar 

  29. Cristofanilli M, Hayes D, Budd GT, et al. Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol. 2005;3:1420–30.

    Article  Google Scholar 

  30. Braun S, Vogl FD, Naume B, et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 2005;353(8):793–802.

    Article  CAS  PubMed  Google Scholar 

  31. Cohen SJ, Punt CJ, Iannotti N, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(19):3213–21.

    Article  PubMed  Google Scholar 

  32. Sandri MT, Zorzino L, Cassatella MC, Bassi F, Luini A, et al. Changes in circulating tumor cell detection in patients with localized breast cancer before and after surgery. Ann Surg Oncol. 2010;17:1539–45.

    Article  PubMed  Google Scholar 

  33. Ring A, Smith IE, Dowsett M. Circulating tumour cells in breast cancer. Lancet Oncol. 2004;5:79–88.

    Article  PubMed  Google Scholar 

  34. Tibbe AG, Miller MC, Terstappen LW. Statistical considerations for enumeration of circulating tumor cells. Cytometry A. 2007;71:154–62.

    Article  PubMed  Google Scholar 

  35. Allard WJ, Matera J, Miller MC, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004;10:6897–904.

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bin Xiong.

Additional information

Yi Liao and Shu-Yi Wang have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liao, Y., Wang, SY., Meng, XY. et al. Circulating tumor cells in breast cancer and its association with tumor clinicopathological characteristics: a meta-analysis. Med Oncol 31, 343 (2014). https://doi.org/10.1007/s12032-014-0343-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0343-7

Keywords

Navigation