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Poster session 02

195P - Breast cancer molecular subtypes markers in subpopulations of circulating tumor cells

Date

10 Sep 2022

Session

Poster session 02

Topics

Cancer Biology;  Molecular Oncology

Tumour Site

Breast Cancer

Presenters

Evgeniya Grigoryeva

Citation

Annals of Oncology (2022) 33 (suppl_7): S55-S84. 10.1016/annonc/annonc1038

Authors

E. Grigoryeva1, O.E. Savelieva2, L. Tashireva2, V.V. Alifanov3, V. Yakushina4, N.A. Tarabanovskaya5, N. Cherdyntseva1, V. Perelmuter2

Author affiliations

  • 1 Laboratory Of Molecular Oncology And Immunology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 - Tomsk/RU
  • 2 General And Molecular Pathology Department, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 - Tomsk/RU
  • 3 General And Molecular Pathology Department, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634028 - Tomsk/RU
  • 4 Laboratory Of Genome Editing, Research Centre for Medical Genetics, 115522 - Mocow/RU
  • 5 Department Of General Oncology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 - Tomsk/RU

Resources

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Abstract 195P

Background

Molecular subtype of breast cancer is a criterion that determines the treatment tactic and the prognosis of the clinical course of the disease. At the same time, CTCs can arise from the minor subpopulation of primary tumor cells, that do not express target molecules for prescribed therapy. Here we assessed the presence of ER/PR/Her2+ and Ki-67 in subpopulations of CTCs with different manifestations of EMT and stemness, which could dramatically effect on their capacity to migration, proliferation and finally forming a clinically detectable macrometastsis.

Methods

The prospective study included 84 breast cancer patients with stage T2-4N0-3M0. CTCs were detected only in 45 out 84 cases (54%). 256 phenotypes of CTCs were detected by flow cytometry (Novocyte 3000, ACEA Biosciences, USA) using monoclonal antibody cocktail.

Results

Patients were represented in a two-dimensional tSNE plane, and two clusters were identified via principal component analysis (PCA). In patients belonging to cluster 2 the number of CTCs was 3 times higher (p=0,00002). Cluster 1 included patients with three molecular subtypes (luminal A, luminal B, triple-negative (TN)), while cluster 2 was represented only by luminal subtypes. There were more patients with luminal A subtype in cluster 2 (p=0,06). Only 6 CTCs phenotypes were significantly different in two clusters. All phenotypes were characterized by absence of EMT traits and did not have the ability to proliferate. It is noteworthy that in cluster 2 the TN phenotypes of CTCs were predominant, while there were no patients with TN molecular subtype this cluster. A comparative analysis of the two clusters, depending on the clinicopathological parameters, revealed significant differences between patients having menstrual cycle and menopausal patients in cluster 2. Menopausal patients had more CTCs corresponding to TN phenotype, with no features of stemness, EMT and proliferation. Subpopulation of CTCs corresponding to luminal A subtype, with CD133 expression, without traits of EMT and proliferation, on the contrary, were less in menopausal patients.

Conclusions

The presence of CTCs corresponding to TN subtype in the cluster 2 confirms the possibility of tumor cells to converse molecular subtype during extravasation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Russian Science Foundation (grant #19-75-30016).

Disclosure

All authors have declared no conflicts of interest.

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