Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Comments on “Detection of circulating tumour cells before and following adjuvant chemotherapy and long-term prognosis of early breast cancer”

British Journal of Cancer volume 126, pages 1659–1660 (2022)Cite this article

Subjects

We have read with great interest the recently published manuscript by Alexios Matikas et al. [1], which concludes detection of circulating tumour cells (CTC) before and following adjuvant chemotherapy in early breast cancer patients has significant prognostic implications. In this article, the authors have presented the survival data of 1220 patients with breast cancer who were tested positive for CTCs detected by the in-house methods developed by the authors. The authors followed up the patients for a median period of 134.1 months, both clinically and with detection of CTCs in various time points during the follow-up. There is a significant increase in the overall survival of the patients with CTC negativity status in both baseline and during follow-up. From our point of view, the study is very interesting and presented a significant clinical insight into the importance of CTC detection for breast cancer patients, mainly when presented in the early stage. However, we feel that some important issues merit more discussion while using the finding of this study for clinical purposes.

Firstly, the authors used the CTC detection technique using a qPCR-based identification strategy based on their previous publication [2]. Although the strategy has been compared with two other strategies for detecting CTCs in breast cancer, it has its limitations [3]. In short, the strategy uses detection of CK19 mRNA in peripheral blood mononuclear cells (PBMCs) using qPCR. Detection of CK19 mRNA positive CTCs by this strategy has 62% agreement with FDA approved CellSearchTM strategy in the case of early breast cancer and 63.4% for metastatic breast cancer [3]. We would like to highlight the potential drawback of the strategy, which significantly impacts the results presented in the study and merits detailed discussion. Various studies have reported that a significant number of CTCs in breast cancer patients are CK19 negative [4]. It has also been reported that the CTCs are inherently heterogeneous, and these heterogeneous CTCs are associated with metastasis [5]. Similarly, it is expected that CTCs in the patient cohort presented by the authors in this study must have had similar heterogeneity. Again those CTCs which were CK19 negative could not be detected, resulting in a lower number of detection. Moreover, it is reported that the presence of CTCs with mesenchymal markers and CTCs presented with weak CK19 expression or loss of CK19 expression results in higher metastasis in breast cancer patients [6, 7]. As a result, the data related to the detection of CTCs at various time points presented by the authors in the current study may not have depicted the actual number of CTCs present and their heterogeneous phenotypes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Matikas A, Kotsakis A, Apostolaki S, Politaki H, Perraki M, Kalbakis K, et al. Detection of circulating tumour cells before and following adjuvant chemotherapy and long-term prognosis of early breast cancer. Br J Cancer. 2022. https://doi.org/10.1038/s41416-022-01699-5.

  2. Stathopoulou A, Gizi A, Perraki M, Apostolaki S, Malamos N, Mavroudis D, et al. Real-time quantification of CK-19 mRNA-positive cells in peripheral blood of breast cancer patients using the lightcycler system. Clin Cancer Res. 2003;9:5145–51.

    CAS  PubMed  Google Scholar 

  3. Politaki E, Agelaki S, Apostolaki S, Hatzidaki D, Strati A, Koinis F, et al. A comparison of three methods for the detection of circulating tumor cells in patients with early and metastatic breast cancer. Cell Physiol Biochem. 2017;44:594–606.

    Article  Google Scholar 

  4. Xu L, Jia S, Li H, Yu Y, Liu G, Wu Y, et al. Characterization of circulating tumor cells in newly diagnosed breast cancer. Oncol Lett. 2018;15:2522–8.

    PubMed  Google Scholar 

  5. Hassan S, Blick T, Thompson EW, Williams ED. Diversity of epithelial-mesenchymal phenotypes in circulating tumour cells from prostate cancer patient-derived xenograft models. Cancers. 2021;13:2750.

    Article  CAS  Google Scholar 

  6. Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science. 2013;339:580–4. https://doi.org/10.1126/science.1228522.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Topa J, Grešner P, Żaczek AJ, Markiewicz A. Breast cancer circulating tumor cells with mesenchymal features-an unreachable target? Cell Mol Life Sci. 2022;79:81.

    Article  CAS  Google Scholar 

  8. Drucker A, Teh EM, Kostyleva R, Rayson D, Douglas S, Pinto DM. Comparative performance of different methods for circulating tumor cell enrichment in metastatic breast cancer patients. PLoS ONE. 2020;15:e0237308.

    Article  CAS  Google Scholar 

  9. Augustyn A, Adams DL, He J, Qiao Y, Verma V, Liao Z, et al. Giant circulating cancer-associated macrophage-like cells are associated with disease recurrence and survival in non-small-cell lung cancer treated with chemoradiation and atezolizumab. Clin Lung Cancer. 2021;22:e451–65.

    Article  CAS  Google Scholar 

  10. https://www.proteinatlas.org/ENSG00000171345-KRT19/summary/rna. Accessed 18 Feb 2022.

Download references

Acknowledgements

AC has been supported by CSIR-NET fellowship Grant no: 09/141 (0209)/2019- EMRI

Author information

Authors and Affiliations

  1. Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Anshika Chauhan & Arnab Pal

Authors
  1. Anshika Chauhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arnab Pal
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both AC and AP drafted the correspondence

Corresponding author

Correspondence to Arnab Pal.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chauhan, A., Pal, A. Comments on “Detection of circulating tumour cells before and following adjuvant chemotherapy and long-term prognosis of early breast cancer”. Br J Cancer 126, 1659–1660 (2022). https://doi.org/10.1038/s41416-022-01804-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41416-022-01804-8

Search

Advanced search

Quick links