Predictive and prognostic significance of stemness gene amplifications in the breast tumor in patients who received neoadjuvant chemotherapy


P.V. Kazantseva (1), E.M. Slonimskaya (1, 2), M.M. Tsyganov (1), M.K. Ibragimova (1, 3), A.V. Doroshenko (1), N.A. Tarabanovskaya (1), N.V. Litviakov (1, 3)

1) Scientific Research Institute of Oncology, Tomsk National Research Medical Center of RAS, Tomsk, Russia; 2) Siberian State Medical University, Tomsk, Russia; 3) National Research Tomsk State University, Tomsk, Russia
Background. There is evidence that neoadjuvant chemotherapy (NACT) in some cases stimulates metastasis of breast cancer (BC), and the increased aggressiveness and metastasis of the tumor under the action of chemotherapy are associated with stimulation of tumor stem cells, the activity of which is determined by increased expression of stemness genes (SG). New tumor markers associated with a high risk of disease progression against the background of the treatment are required, and it has a greatest importance for patients receiving NACT in the preoperative period.
Objective. Assessment of the immediate effectiveness of NACT and metastatic-free survival in patients with breast cancer depending on the presence of amplifications of regions of SG localization. in the primary breast tumor.
Methods. Evaluation of the predictive and prognostic significance of the presence of amplifications of the SG loci 3q, 5p, 6p, 7q, 8q, 9p, 9q, 10p, 10q21.1, 12p, 13q, 16p, 18q, 19p in a breast tumor was carried out before treatment in 103 patients receiving NACT. Depending on the number of amplifications in the tumor, the patients were divided into two groups: with the presence of ≥2 amplifications in the tumor and with or without a single stemness gene amplification. SG amplification was determined using a high density CytoScanTM HD Array, Affymetrix (USA).
Results. It has been established that SG amplifications in the primary tumor do not have predictive significance. The main result of the study was the identification of their prognostic significance. It was shown that the achievement of both complete and partial regression of neoplasm against NACT in breast cancer patients with ≥2 amplifications of any regions of SG localization in primary tumor tissue leads to a significant increase in metastatic-free survival (Log Rank [Mantel-Cox] p=0,025). At the same time, even a good response to NACT does not lead to an increase in the survival rate of patients with 0–1 amplification of SG.
Conclusion. Thus, the results show that only patients with ≥2 SG amplifications have benefit from the treatment with NACT in terms of increasing survival, and these patients should receive NACT.
Keywords: breast cancer, prognostic criteria, stemness gene amplification

About the Autors

Corresponding author: Polina V. Kazantseva, PhD, Researcher at the Department of General Oncology, Scientific Research Institute of Oncology, Tomsk National Research Medical Center of RAS, Tomsk, Russia; e-mail:
Address: 5, Kooperativny Lane, Tomsk, 634050, Russian Federation

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