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
CNA-bearing tumor clones decreased following NAC; 2 – there were no alterations in the
number of CNA-containing 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 may be 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.