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Dynamic changes of CTCs in patients with metastatic HR(+)/HER2(−) breast cancer receiving salvage treatment with everolimus/exemestane

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Abstract

Purpose

Detection of CTCs represents a poor prognostic factor in patients with early and metastatic breast cancer (mBC) and treatment with everolimus–exemestane (E/E) is an established effective treatment in hormone receptor-positive/HER2-negative mBC patients. The effect of E/E on CTCs in mBC patients was prospectively investigated.

Methods

CTCs from 50 pre-treated patients with mBC receiving E/E were analyzed using the CellSearch (CS) platform and triple immunofluorescence (IF) staining for cytokeratin, M30 and Ki67 expression to assess their proliferative and apoptotic status.

Results

CTCs (by CS) were detected in 64% of patients before treatment and E/E administration resulted in their decreased prevalence [(n = 18; 36%, p = 0.004) and (n = 7; 19.4%, p = 0.019) post-1st and post-3rd treatment cycle, respectively] whereas it was significantly increased at disease progression (PD: 61%) compared to post-1st and post-3rd cycle (p = 0.049 and p = 0.021, respectively). Ki67-positive CTCs were detected in 60%, 60%, 17% and 50% of patients before treatment, post-1st, post-3rd cycle and at PD, respectively, while the opposite was observed for M30-positive CTCs (0% at baseline, 10% after the 1st cycle, 50% after the 3rd cycle and 0% at PD). The detection of even ≥ 1 CTC/5 ml after one cycle was associated with decreased PFS (3.3 vs 9.0 months, p = 0.025) whereas the detection of even ≥ 2 CTCs at PD was associated with decreased OS (32.4 vs 19.5 months; p = 0.009).

Conclusions

The combination of E/E resulted in early elimination of proliferating CTCs in mBC patients and this effect was associated with a favorable clinical outcome.

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Acknowledgements

This work was funded by the Hellenic Oncology Research Group (HORG), the Hellenic Society of Medical Oncology (HeSMO) and the Cretan Association for Biomedical Research (CABR). We would like to thank Ms Vasso Athanasaki for her attentive editing of this manuscript.

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  1. Maria Spiliotaki and Galatea Kallergi have equal contribution.

Authors and Affiliations

  1. Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Crete, Greece

    Maria Spiliotaki, Christos Nikolaou, Eleni Politaki, Stella Apostolaki, Filippos Koinis, Dora Hatzidaki, Athanasios Kotsakis & Vassilis Georgoulias

  2. Department of Biochemistry, University of Crete Medical School, Heraklion, Crete, Greece

    Galatea Kallergi

  3. Hellenic Oncology Research Group (HORG), 55 Lombardou str, 11474, Athens, Greece

    Nikolaos Xenidis, Nefeli Georgoulia, Filippos Koinis, Nikolaos Tsoukalas, Dora Hatzidaki, Athanasios Kotsakis & Vassilis Georgoulias

  4. Department of Medical Oncology, Medical School, Democritus University of Thrace, Xanthi, Greece

    Nikolaos Xenidis

  5. Department of Medical Oncology, Faculty of Medicine, School of Health Sciences, University Hospital of Larissa & Laboratory of Oncology, University of Thessaly Mezourlo, Larissa, Thessaly, Greece

    Filippos Koinis & Athanasios Kotsakis

  6. Medical Oncology Unit, NIMITS Hospital, Athens, Greece

    Nikolaos Tsoukalas

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  1. Maria Spiliotaki
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Contributions

All the authors contributed to the study conception and design. GK and VG conceived and designed the study; MS, GK, ChN, NX, EP, SA, NG, FK, NT, DH, AK, and VG acquired, analyzed, and interpreted the data, or made key methodological contributions; MS, GK, and VG wrote the paper; VG supervised the study. All the authors read and approved the final manuscript.

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Correspondence to Vassilis Georgoulias.

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Spiliotaki, M., Kallergi, G., Nikolaou, C. et al. Dynamic changes of CTCs in patients with metastatic HR(+)/HER2(−) breast cancer receiving salvage treatment with everolimus/exemestane. Cancer Chemother Pharmacol 87, 277–287 (2021). https://doi.org/10.1007/s00280-020-04227-5

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