Clinical review for general practice

ISSN (Print) 2713-2552
ISSN (Online) 2782-5671
  • Home
  • about
  • archives
  • contacts
left
FULLSCREEN > Archive > 2025 > Vol 6, №9 (2025) > The effect of circulating tumor cells on prognosis in patients with advanced breast cancer

The effect of circulating tumor cells on prognosis in patients with advanced breast cancer

Iman A.A. Abdo , Natalia A. Falaleeva , Luydmila Yu. Grivtsova , Anastasia B. Galitsyna , Irina S. Pimonova , Anna S. Belokhvostova , Aleksandr A. Sofiochuk

For citation:


  • Abstract
  • About the Author
  • References

Abstract

Introduction. Detection of circulating tumor cells (CTCs) correlates with a poor prognosis in metastatic breast cancer (MBC), however, there is clearly insufficient data to prove the level and phenotypic characteristics that are predictors of an unfavorable prognosis. In addition, the high cost and complexity of analyzing test systems registered in the world makes it impossible to conduct routine research and encourages the search for other methods for detecting CTCs, analyzing their characteristics and predictive values. The purpose of this study was to study the effect of CTC on the course of MBC, taking into account their level and qualitative composition using the flow cytometry method in accordance with the original methodology of the A.F. Tsyba MRRC. 
Materials and methods. The study included 21 patients with MBC. The average age of the patients was 52.7 years. The median follow–up was 21.4 months. The absolute majority of patients had involvement of regional lymph nodes in the tumor process (80.9%), metastatic bone damage was most often noted in 17 (80.9%) patients and brain damage in 9 (42.8%) patients. The most common biological subtype of the tumor was the triple negative subtype (28.7%). Before starting therapy, all patients underwent a CTC assessment using the multiparameter flow cytometry method according to the original method of the Tsyba MRSC. Not only the number of CTCs, but also their immunophenotypic features were evaluated based on the analysis of the expression of CAM5.2, BerEP4, HLA antigens-DR and CD95. All patients were treated according to the biological subtype of the tumor in accordance with the clinical recommendations of the Ministry of Health of the Russian Federation. 
Results. CTCs in peripheral blood were detected in 20 patients (95.3%), their number ranged from 1 to 107 cells. We found that the threshold value that significantly affects the prognosis for MBC is 8 CTCs for assessing overall survival (OS) and 5 CTCs for assessing progression-free survival (PFS) in 7.5 ml of blood. Thus, 2-year OS in the group of patients with 8 or more CTC (n=12) was 50%, in the group with less than 8 CTC (n=9) – 77.8% (p=0.1); The 2-year PFS was 5.6% in the group of patients with 5 or more CTC, and 100% in the group with less than 5 CTC (p=0.008). The features of the qualitative composition of the CTC associated with the forecast are established. The group with the CTC immunophenotype CAM5.2+BerEP4+ was prognostically unfavorable compared with the CAM5 group.2+BEREP4 is a 2-year-old OS with the CAM5 phenotype.2+BEREP4+ was 46.2%, with the CAM5 phenotype.2+BEREP4- – 85.7% (p=0.096); 2-year AFD with CAM5 phenotype.2+BEREP4+ was 0%, with the CAM5 phenotype.2+BEREP4- – 42.9% (p=0.002).
Conclusions. CTCs in MBC are detected in 95.3% of cases and represent an immunophenotypically heterogeneous subset of tumor cells in the expression of pan-epithelial markers. The number of CCPs and their qualitative composition are significantly related to the prognosis of MBC.
Keywords: breast cancer, circulating tumor cells, late-stage cancer.

About the Author

Iman A.A. Abdo 1 , Natalia A. Falaleeva 2 3 , Luydmila Yu. Grivtsova 2 , Anastasia B. Galitsyna 2 3 , Irina S. Pimonova 2 , Anna S. Belokhvostova 2 3 , Aleksandr A. Sofiochuk 2

1 Patrice Lumumba People’s Friendship University of Russia (RUDN University), Moscow, Russia

2 Tsyb Medical Radiological Research Centre – branch of the National Medical Research Radiological Centre, Obninsk, Russia

3 Obninsk Institute of Atomic Energy – branch National Research Nuclear University MEPhI, Obninsk, Russia

References

1. Chia SK, Speers CH, D'Yachkova Y et al. The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer 2007;110:973-9. DOI: 10.1002/cncr.22867 
2. Pagani O, Senkus E, Wood W et al. International guidelines for management of metastatic breast cancer: can metastatic breast cancer be cured? J Natl Cancer Inst 2010;102:456-63. DOI: 10.1093/jnci/djq029 
3. Andreopoulou E, Hortobagyi GN. Prognostic factors in metastatic breast cancer: successes and challenges toward individualized therapy. J Clin Oncol 2008;26:3660-2. DOI: 10.1200/JCO.2008.16.1026 
4. Schaffner F, Merlin J-L, von Bubnoff N. Tumor Liquid Biopsies. Springer, 2020. DOI: 10.1007/978-3-030-26439-0 
5. 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. DOI: 10.1056/NEJMoa040766 
6. Dawood S, Broglio K, Valero V et al. Circulating tumor cells in metastatic breast cancer: from prognostic stratification to modification of the staging system? Cancer 2008;113:2422-2430. DOI: 10.1002/cncr.23852 7. Cristofanilli M, Hayes DF, Budd GT et al. Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 2005;23:1420-30. DOI: 10.1200/JCO.2005.08.140 
8. Hayes DF, Cristofanilli M, Budd GT et al. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res 2006;12:4218-24. DOI: 10.1158/1078-0432.CCR-05-2821 
9. Liu MC, Shields PG, Warren RD et al. Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer. J Clin Oncol 2009;27:5153-9. DOI: 10.1200/JCO.2008.20.6664 
10. Burčík D, Macko J, Podrojková N et al. Role of Cell Adhesion in Cancer Metastasis Formation: A Review. ACS Omega 2025;10(6):5193-213. DOI: 10.1021/acsomega.4c08140. PMID: 39989825; PMCID: PMC11840620. 
11. Wei J, Shen Y, Ouyang G. Determination of circulating tumor cells by surface-enhanced Raman scattering based on molecularly imprinted polymers doped with silver nanoparticles. Anal Sci 2025. Feb 25. DOI: 10.1007/s44211-025-00719-7. Epub ahead of print. PMID: 39998807 
12. Зацаренко С.В., Гривцова Л.Ю., Мушкарина Т.Ю. Способ выявления циркулирующих в крови опухолевых клеток методом многопараметровой проточной цитометрии. Патент на изобретение RU 2825188, 21.08.2024, заявка №2024103239 от 09.02.2024. Zatsarenko S.V., Grivtsova L.Yu., Mushkarina T.Yu. A method for detecting tumor cells circulating in the blood by multiparameter flow cytometry. Patent for invention RU 2825188, 08/21/2024, application No. 2024103239 dated 02/09/2024. (in Russian). 
13. Nagata S. Early work on the function of CD95, an interview with Shige Nagata. Cell Death and Differentiation 2004;11(S1):S23-S27. DOI: 10.1038/sj.cdd.4401453. PMID 15143352 
14. Guan X. Cancer metastases: challenges and opportunities. Acta Pharm Sin 2015;5:402-18. DOI: 10.1016/j.apsb.2015.07.005 
15. Chia SK, Speers CH, D’yachkova Y et al. The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer Cancer 2007;110:973-79. 16. Злокачественные новообразования в России в 2023 году (заболеваемость и смертность). Под ред. А.Д. Каприна и др. М.: МНИОИ им. П.А. Герцена − филиал ФГБУ «НМИЦ радиологии», 2024. ISBN: 978-5-85502-298-8. Malignant neoplasms in Russia in 2023 (morbidity and mortality). Edited by A.D. Kaprin et al. Moscow: Herzen Moscow Oncology Research Institute – branch of National Medical Research Center for Radiology, 2024. ISBN: 978-5-85502-298-8 (in Russian). 
17. 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. 
18. Paoletti C, Smerage J, Hayes DF et al. Circulating tumor cells as a marker of prognosis. In: Principle sand Practice of Oncology Updates. Eds: DeVita VT Jr, Lawrence TS, Rosenberg SA. 2012;1-8:26. New York, NY Wolters Kluwer Health, 2012. 
19. Smerageet JB, Barlow WE, Hortobagyi GN et al. Circulating Tumor Cells and Response to Chemotherapy in Metastatic Breast Cancer: SWOGS0500. JCO 2014;32:3483-9. DOI: 10.1200/JCO.2014.56.2561 
20. Dawood S, Broglio K, Valero V et al. Circulating tumor cells in metastatic breast cancer: from prognostic stratification to modification of the staging system? Cancer 2008;113(9):2422-30. DOI: 10.1002/cncr.23852. PMID: 18785255. 
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. DOI: 10.1186/bcr2907. PMID: 21699723; PMCID: PMC3218956. 
22. Chang KL, Chao WR, Han CP. Anticytokeratin (CAM5.2) reagent identifies cytokeratins 7 and 8, not cytokeratin 18. Chest 2014;145(6):1441-2. DOI: 10.1378/chest.14-0168. PMID 24889460BEREP 
23. Sunjaya AP, Sunjaya AF, Tan ST. Ber-EP4 (Epithelial Cell Adhesion Molecule/EPCAM) Immunostain, Technical Component Only. Mayo Clinic Laboratories. Retrieved 2019-12-16. The Use of BEREP4 Immunohistochemistry Staining for Detection of Basal Cell Carcinoma. J Skin Cancer 2017:2692604. DOI: 10.1155/2017/2692604. ISSN 2090-2905. PMC 5804366

For citation:Abdo I.A.A., Falaleeva N.A., Grivtsova L.Yu., Galitsyna A.B., Pimonova I.S., Belokhvostova A.S., Sofiochuk A.A. The effect of circulating tumor cells on prognosis in patients with advanced breast cancer. Clinical review for general practice. 2025; 6 (9): 82–88 (In Russ.). DOI: 10.47407/kr2025.6.9.00677


All accepted articles publish licensed under a Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

  • About
  • Editorial board
  • Ethics
  • For authors
  • Author fees
  • Peer review
  • Contacts

oa
crossref
анри


  Indexing

Scopus
doaj
elibrary

Address of the Editorial Office:

127055, Moscow, s/m 37

Correspondence address:

115054, Moscow, Zhukov passage, 19, fl. 2, room XI


Managing Editor:

+7 (495) 926-29-83

id@con-med.ru