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Response to A. Chauhan and A. Pal

British Journal of Cancer volume 126, pages 1661–1662 (2022)Cite this article

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We would like to thank Chauhan and Pal for their interest in and commentary on our study [1]. In principle, we agree with the comments on the sensitivity of the assay, concordance with CellSearch (Menarini Silicon Biosystems Inc, Italy) and potential advantages of negative cell selection. Sensitivity and concordance are both briefly discussed as limitations, considering the translational scope of our study. However, it should be noted that FDA approval for the CellSearch system is based on the clinical validity of the platform and does not imply that its results are the fundamental ground truth for the presence of CTC, the gold standard all other assays should be compared with. In addition, this regulatory approval was based on the platform’s results in patients with metastatic disease and not in patients with early breast cancer. This could be of special relevance based on the heterogeneity of the disease and its clinical significance during the different clinical phases of breast cancer. Therefore, although we state the modest agreement between the two assays as an observation, we object to the conclusion by Chauhan and Pal that this discordance “…significantly impacts the results presented in the study and merits detailed discussion”. In contrast, the demonstrated prognostic information and potential patient benefit are unrelated to these issues.

Nevertheless, this assay was first published in detail in 2003 [2]. This initial publication was followed by numerous studies that have discussed its analytical performance, biologic correlations and clinical validity for early breast cancer in great depth [3,4,5,6,7,8], even demonstrating potential clinical utility in a prospective randomised trial [9]. We feel thus that extensive repetition of previously presented information is outside the scope of this specific study, as the reader can refer to previous publications. Here we showed that a low-cost PCR assay which can be delivered at the point of care without requiring proprietary equipment or consumables, with low need for manual labour or specialised training, provides robust and consistent prognostic information, despite its theoretical shortcomings. Whether other assays, that include negative selection of cells or that detect heterogeneous CTC populations, offer additional prognostic information and lead to clear advantages in patient selection for alternative adjuvant strategies should be the subject of future studies. Crude comparisons regarding the detection rate of CTC however are not an endpoint that readily translates to patient benefit.

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References

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Authors and Affiliations

  1. Department of Oncology-Pathology, Karolinska Institutet Stockholm, Stockholm, Sweden

    Alexios Matikas

  2. Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden

    Alexios Matikas

  3. Laboratory of Tumor Cell Biology, University of Crete, Heraklion, Greece

    Vassilis Georgoulias

  4. Hellenic Oncology Research Group, Athens, Greece

    Vassilis Georgoulias

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  1. Alexios Matikas
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Both authors drafted the reply to the commentary.

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Correspondence to Alexios Matikas.

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AM: consultancy to Veracyte, CA, USA (no financial compensation); VG: research grants from Novartis, Astellas, Astra Zeneca, Pfizer.

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Matikas, A., Georgoulias, V. & and on behalf of the authors. Response to A. Chauhan and A. Pal. Br J Cancer 126, 1661–1662 (2022). https://doi.org/10.1038/s41416-022-01803-9

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