Title:Neoadjuvant Chemotherapy Induces the Appearance of New Copy Number Aberrations in Breast Tumor and is Associated with Metastasis
Volume: 20
Issue: 9
Author(s): Nikolai V. Litviakov*, Marina K. Ibragimova, Matvey M. Tsyganov, Artem V. Doroshenko, Eugeniy Y. Garbukov and Elena M. Slonimskaya
Affiliation:
- Laboratory of Oncovirology, Cancer Research Institute, Tomsk National Research Medical Center, Russia Academy of Science, Tomsk,Russian Federation
Keywords:
Clonal evolution, breast cancer, chemotherapy, copy number aberration, metastasis, CNA-genetic landscape.
Abstract:
Background: In this study, we examined the CNA-genetic landscape (CNA – copy number
aberration) of breast cancer prior to and following neoadjuvant chemotherapy (NAC) and correlated
changes in the tumor landscape with chemotherapy efficiency as well as metastasis-free survival.
Objective: Breast cancer patients (n = 30) with luminal B molecular subtypes were treated with anthracycline-
based therapy.
Methods: To study CNAs in breast tumors, microarray analysis was performed.
Results: Three effects of NAC on tumor CNA landscape were identified: 1 - the number of CNAbearing
tumor clones decreased following NAC; 2 - there were no alterations in the number of CNAcontaining
clones after NAC; 3 - the treatment with NAC increased the number of CNA-bearing
clones (new clones appeared). All NAC-treated patients who had new tumor clones with amplification
(20%) had a 100% likelihood of metastasis formation. In these cases, NAC contributed to the
emergence of potential metastatic clones. Our study identified the following loci - 5p, 6p, 7q, 8q, 9p,
10p, 10q22.1, 13q, 16p, 18Chr and 19p - that were amplified during the treatment with NAC and
maybe the markers of potential metastatic clones. In other patients who showed total or partial
elimination of CNA-bearing cell clones, no new amplification clones were observed after NAC, and
no evidence of metastases was found with follow-up for 5 years (р = 0.00000).
Conclusion: Our data suggest that the main therapeutic result from NAC is the elimination of potential
metastatic clones present in the tumor before treatment. The results showed the necessity of an
intelligent approach to NAC to avoid metastasis stimulation.
