Abstract
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 (n = 41), in the presence of two or more amplifications, patients were prescribed a personalized NAC regimen. In group 2 (n = 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 (n = 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.
Highlights
An increasing number of works are devoted to the fact that chemotherapy and targeted therapy in some patients can stimulate the formation of new mutations, which leads to the formation of treatment resistance and tumor metastasis [1,2]
Neoadjuvant chemotherapy in some patients stimulated breast cancer metastasis [9] and facilitated the progression of the metastatic process: stimulating EMT in tumor cells, invasion, intravasation and inflammation [10]. It has been demonstrated in experimental models that, in some cases, chemotherapy can significantly enhance the invasive properties of tumor cells and promote the formation of metastatic niches and the ability to extravasate [11,12]
It is time to review the indications for neoadjuvant chemotherapy (NAC) and to emphasize other aspects of treatment, which would take the rate of chemoinduced evolution of tumor cells in the patient and the probability of the formation of treatment resistance and tumor metastasis into account
Summary
An increasing number of works are devoted to the fact that chemotherapy and targeted therapy in some patients can stimulate the formation of new mutations, which leads to the formation of treatment resistance and tumor metastasis [1,2]. Such data were presented for many types of cancer, such as acute lymphoblastic leukemia [3], chronic lymphocytic leukemia [4], acute myeloid leukemia [5], esophageal adenocarcinoma [6], glioblastoma [7], and lung cancer [8]. Neoadjuvant chemotherapy in some patients stimulated breast cancer metastasis [9] and facilitated the progression of the metastatic process: stimulating EMT (epithelial-mesenchymal transition) in tumor cells, invasion, intravasation and inflammation [10]. Preoperative chemotherapy is a kind of competition between the rate of the elimination of tumor cells and the rate of clonal chemoinduced evolution of tumor cells
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