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Molecular subtype of breast cancer has a great clinical significance and used as one of the major criteria for therapeutic strategy. Recently, for anticancer therapy, the trend for oncologists is the predominant determination of biomarkers in the existing foci of the disease. In the case of adjuvant therapy prescribed for distant metastases prevention, CTCs could be a suitable object for investigation. CTCs as one of the factors responsible for tumor metastatic potential could be more convenient and informative for evaluation of hormone receptors, Ki-67 and HER2 expression, which are determine molecular subtype in breast cancer patient. In our study, we aimed to investigate the molecular subtype discordance between the primary tumor and CTCs in breast cancer patients. We established conversion of molecular subtype in most of the cases. Namely, conversion was detected in 90% of untreated patients and in 82% of breast cancer patients treated by neoadjuvant chemotherapy. At the same time, molecular subtype conversions in patients treated by neoadjuvant chemotherapy were more diverse. Molecular subtype conversions resulted more often in the unfavorable variants in circulating tumor cells. We stratified all patients according to the adequacy of treatment against converted CTCs molecular subtype. Our study revealed that good response to neoadjuvant chemotherapy observed in case of adequate therapy, namely, when chemotherapy scheme was sufficient against CTCs. It turned out that patients with inadequate therapy were characterized by decreased simulated 5-year metastasis-free survival compared to patients who received appropriate therapy. Thus, detection of molecular subtype conversion in circulating tumor cells could be a perspective tool for optimization of antitumor therapy. [ABSTRACT FROM AUTHOR]

Aim. To investigate the expression of the TGFB1, TNF, CSF1, CSF2, VEGFA and HIF1A genes in the patients with invasive breast carcinoma of no special type considering the intratumoral morphological heterogeneity. Methods. The technology of laser capture microdissection PALM was used to isolate five types of morphological tumor structures from three patients with invasive carcinoma of no special type (IC NST), luminal A subtype, T1-2NxMx. The level of expression of the cytokine (TNF), growth factors (TGFB1, CSF1, CSF2, VEGFA) and the HIF1A genes was assessed in the samples obtained using quantitative real-time PCR. Results. The study demonstrated the absence of the expression of the growth factor CSF2 gene in tumor cells of IC NST, and the expression of the CSF1 gene, independent from the metastasis status and tumor structure type. The prevalence of the expression of the VEGFA and TGFB1 genes was revealed in the alveolar and solid structures along with the rare expression of the TNF gene. Conclusions. The expression of pre-metastatic niche genes in the tumors of patients with IC NST is heterogeneous. The hypoxia-mediated change in the cytokine gene expression may be expected in the alveolar and solid structures, which ultimately results in the formation of microenvironment, facilitating tumor growth and the formation of tumor metastatic potential. [ABSTRACT FROM AUTHOR]