Amplifications of Stemness Gene Loci—New Markers for the Determination of the Need for Neoadjuvant Chemotherapy for Patients with Breast Cancer. A Prospective Study

In this prospective study, a new strategy for the prescription of neoadjuvant chemotherapy (NAC) was prospectively tested and depended on the presence of stemness gene amplifications in the tumor before treatment, which in our early studies showed a connection with metastasis. The study included 92...

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Main Authors: Nikolai V. Litviakov, Marina K. Ibragimova, Matvey M. Tsyganov, Polina V. Kazantseva, Artem V. Doroshenko, Eugeniy Yu. Garbukov, Irina G. Frolova, Elena M. Slonimskaya
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Journal of Personalized Medicine
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Online Access:https://www.mdpi.com/2075-4426/11/5/397
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author Nikolai V. Litviakov
Marina K. Ibragimova
Matvey M. Tsyganov
Polina V. Kazantseva
Artem V. Doroshenko
Eugeniy Yu. Garbukov
Irina G. Frolova
Elena M. Slonimskaya
author_facet Nikolai V. Litviakov
Marina K. Ibragimova
Matvey M. Tsyganov
Polina V. Kazantseva
Artem V. Doroshenko
Eugeniy Yu. Garbukov
Irina G. Frolova
Elena M. Slonimskaya
author_sort Nikolai V. Litviakov
collection DOAJ
description In this prospective study, a new strategy for the prescription of neoadjuvant chemotherapy (NAC) was prospectively tested and depended on the presence of stemness gene amplifications in the tumor before treatment, which in our early studies showed a connection with metastasis. The study included 92 patients with grade IIA–IIIB luminal B breast cancer. Patients underwent a biopsy before treatment, and with the use of a CytoScan HD Array microarray (Affymetrix, Santa Clara, CA, USA), the presence of stemness gene amplifications (3q, 5p, 6p, 7q, 8q, 13q, 9p, 9q, 10p, 10q21.1, 16p, 18chr, 19p) in the tumor was determined. In group 1 (<i>n</i> = 41), in the presence of two or more amplifications, patients were prescribed a personalized NAC regimen. In group 2 (<i>n</i> = 21), if there was no amplification of stemness genes in the tumor, then patients were not prescribed NAC, and treatment began with surgery. Group 3 (<i>n</i> = 30) served as a historical control. The frequency of an objective response to NAC in groups 1 and 3 was 79%. Nonmetastatic survival was found in 100% of patients in group 2, who did not undergo NAC. In patients in group 1, the frequency of metastasis was 10% (4/41). At the same time, in patients in group 3, who received NAC, the rate of metastasis was 47% (14/30). The differences between group 1 and group 3 and between group 2 and group 3 were statistically significant, both by Fisher’s criterion and a log-rank test. The appointment of NAC was most feasible in patients with clones with stemness gene amplifications in the primary tumor, while in the absence of amplifications, preoperative chemotherapy led to a sharp decrease in metastasis-free survival. This strategy of NAC prescription allowed us to achieve 93% metastatic survival in patients with breast cancer.
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spelling doaj.art-c565c6bc1eac4b71b354c1496fa3252b2023-11-21T19:10:07ZengMDPI AGJournal of Personalized Medicine2075-44262021-05-0111539710.3390/jpm11050397Amplifications of Stemness Gene Loci—New Markers for the Determination of the Need for Neoadjuvant Chemotherapy for Patients with Breast Cancer. A Prospective StudyNikolai V. Litviakov0Marina K. Ibragimova1Matvey M. Tsyganov2Polina V. Kazantseva3Artem V. Doroshenko4Eugeniy Yu. Garbukov5Irina G. Frolova6Elena M. Slonimskaya7Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, RussiaCancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, RussiaCancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, RussiaCancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, RussiaCancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, RussiaCancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, RussiaCancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, RussiaCancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, RussiaIn this prospective study, a new strategy for the prescription of neoadjuvant chemotherapy (NAC) was prospectively tested and depended on the presence of stemness gene amplifications in the tumor before treatment, which in our early studies showed a connection with metastasis. The study included 92 patients with grade IIA–IIIB luminal B breast cancer. Patients underwent a biopsy before treatment, and with the use of a CytoScan HD Array microarray (Affymetrix, Santa Clara, CA, USA), the presence of stemness gene amplifications (3q, 5p, 6p, 7q, 8q, 13q, 9p, 9q, 10p, 10q21.1, 16p, 18chr, 19p) in the tumor was determined. In group 1 (<i>n</i> = 41), in the presence of two or more amplifications, patients were prescribed a personalized NAC regimen. In group 2 (<i>n</i> = 21), if there was no amplification of stemness genes in the tumor, then patients were not prescribed NAC, and treatment began with surgery. Group 3 (<i>n</i> = 30) served as a historical control. The frequency of an objective response to NAC in groups 1 and 3 was 79%. Nonmetastatic survival was found in 100% of patients in group 2, who did not undergo NAC. In patients in group 1, the frequency of metastasis was 10% (4/41). At the same time, in patients in group 3, who received NAC, the rate of metastasis was 47% (14/30). The differences between group 1 and group 3 and between group 2 and group 3 were statistically significant, both by Fisher’s criterion and a log-rank test. The appointment of NAC was most feasible in patients with clones with stemness gene amplifications in the primary tumor, while in the absence of amplifications, preoperative chemotherapy led to a sharp decrease in metastasis-free survival. This strategy of NAC prescription allowed us to achieve 93% metastatic survival in patients with breast cancer.https://www.mdpi.com/2075-4426/11/5/397breast cancerneoadjuvant chemotherapystemness genesmarkers of metastasisprospective study
spellingShingle Nikolai V. Litviakov
Marina K. Ibragimova
Matvey M. Tsyganov
Polina V. Kazantseva
Artem V. Doroshenko
Eugeniy Yu. Garbukov
Irina G. Frolova
Elena M. Slonimskaya
Amplifications of Stemness Gene Loci—New Markers for the Determination of the Need for Neoadjuvant Chemotherapy for Patients with Breast Cancer. A Prospective Study
Journal of Personalized Medicine
breast cancer
neoadjuvant chemotherapy
stemness genes
markers of metastasis
prospective study
title Amplifications of Stemness Gene Loci—New Markers for the Determination of the Need for Neoadjuvant Chemotherapy for Patients with Breast Cancer. A Prospective Study
title_full Amplifications of Stemness Gene Loci—New Markers for the Determination of the Need for Neoadjuvant Chemotherapy for Patients with Breast Cancer. A Prospective Study
title_fullStr Amplifications of Stemness Gene Loci—New Markers for the Determination of the Need for Neoadjuvant Chemotherapy for Patients with Breast Cancer. A Prospective Study
title_full_unstemmed Amplifications of Stemness Gene Loci—New Markers for the Determination of the Need for Neoadjuvant Chemotherapy for Patients with Breast Cancer. A Prospective Study
title_short Amplifications of Stemness Gene Loci—New Markers for the Determination of the Need for Neoadjuvant Chemotherapy for Patients with Breast Cancer. A Prospective Study
title_sort amplifications of stemness gene loci new markers for the determination of the need for neoadjuvant chemotherapy for patients with breast cancer a prospective study
topic breast cancer
neoadjuvant chemotherapy
stemness genes
markers of metastasis
prospective study
url https://www.mdpi.com/2075-4426/11/5/397
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