T15

Abstract

Background

Despite the abundance of theoretical evidences displaying the considerable role of the “soil” in metastasis progression, the majority of cancer research and cancer therapy pathogenetic methods focused mainly on the tumor cells. There is still no clear clinical data showing the role of “soil” in the metastasis. Identification of factors and mechanisms driving the conditions promoting tumor dissemination may lead to therapeutic strategy to detect and prevent metastases at the earliest step. It has been established that bone marrow-derived hematopoietic progenitor cells home to pre-metastatic sites before tumor cells infiltrate in these sites. These hematopoietic progenitor cells form regulatory cell cluster of stromal microenvironment (premetastatic niche) to promote secondary tumor growth. In this context, the aim of our study was to evaluate the level of different pools of circulating tumor cells and bone marrow progenitor cells in the blood of patients with breast cancer in the dynamics of neoadjuvant chemotherapy.

Materials and methods

Patients (prospective study) with newly diagnosed invasive breast cancer in the age range 18–50 years and tumor volume of 2.0(> or =) cm, referred at the Tomsk Cancer Research Institute for treatment were included into the study. Eligibility criteria were as follows: the patient’s informed consent to participate in research; morphologically verified diagnosis of invasive carcinoma of non-specific type; luminal B-1, -2, triple negative (basal-like subtype included), HER2 positive breast cancer; T2-4N0-3M0; preserved menstrual function; satisfactory performance status (on a scale (< or =) ECOG 2). Exclusion Criteria were: other than luminal histological type of breast cancer, multiple primary cancer; chronic inflammatory diseases in the acute stage. Samples of venous blood taken from breast cancer patients before biopsy, after biopsy and after each subsequent course of neoadjuvant chemotherapy (NACHT) were served as a study material. The various pools of circulating tumor cells and bone-marrow derived progenitor cells were determined using monoclonal antibodies to EpCam, CD44, CD45, CD24, N-cadherin, CD34, CD133, CD202, VEGFR1 and CD90, labeled with different fluorochromes on flow cytometry BD FACSCanto ™ II.

Results

The study showed that each succeeding course of NACHT increased blood levels of circulating tumor cells, and bone marrow progenitor cells with a phenotype characteristic of EPC (endothelial progenitor cells) (CD34 + CD45–VEGFR + CD133 + CD202 +) and MSC (mesenchymal progenitor stem cells fibroblasts) (CD34–CD90 + VEGFR1–CD45–CD202–). Influence of the NACHT on hematopoietic stem cells HSC (VEGFR1 + CD34 + CD45lowSD202–) and progenitor cells HPC – CD34 + CD45 + CD90–VEGFR1 + CD133 – was ambiguous.

Conclusion

Neoadjuvant chemotherapy increases blood levels of circulating tumor cells, endothelial progenitor cells and mesenchymal stem cells progenitor fibroblasts, thus promoting the formation of premetastatic niche.

The study was conducted with financial support from the Council for Grants of the President of the Russian Federation (Russia) for the state support of young philosophy doctors, agreements of SC 114.120.14.168-MD Russian Scientific Foundation (Russia), Grant No. 14-15-00318 (sample collection) and Russian Foundation for Basic Research (Russia), Grant No. 15-34-20864. We acknowledge support of this work by the Tomsk State University Competitiveness Improvement Program (Russia).