Whole transcriptome analysis of breast tumors during neoadjuvant chemotherapy: association with response to preoperative chemotherapy

Abstract

Introduction. Treatment of breast cancer often includes systemic neoadjuvant chemotherapy. The frequency of complete morphological response varies significantly depending on the molecular subtype of tumor. However, even in triple negative breast cancer, which is considered the most sensitive, it does not exceed 50 %. Therefore, the search for new genetic predictors of tumor response to preoperative treatment, as well as the assessment of tumor changes during neoadjuvant chemotherapy are highly relevant.Objective – to perform whole-transcriptome analysis of breast cancer during neoadjuvant chemotherapy depending on tumor response to preoperative treatment.Materials and methods. This study included 39 patients with luminal B HER2-positive (human epidermal growth factor receptor 2) breast cancer who received 6 to 8 cycles of neoadjuvant chemotherapy. We performed whole-transcriptome analysis of paired biopsy and surgical specimens using the Clariom™ S Assay, human (Affymetrix, USA).Results. We observed significant differences in the pretreatment expression of 166 genes (13 were up-regulated and 153 were down-regulated) between patients with objective response to therapy and those without it. Comparison of preand post-treatment expression profiles demonstrated 680 differentially expressed genes in patients with complete and partial response and 3240 differentially expressed genes in patients with stable or progressive disease. Venn diagram showed that patients with and without objective response to neoadjuvant chemotherapy shared 105 differentially expressed genes.Conclusion. We performed primary screening of genes in breast tumors before therapy and identified genes whose pretreatment expression differed significantly between patients with objective response to neoadjuvant chemotherapy and those without it. Further validation of these genes in an independent sample will allow the development of a genetic panel to evaluate the response to neoadjuvant chemotherapy. Assessment of changes in the expression of tumor genes during treatment depending on patient’s response to therapy can be useful for further development of a panel of genes, which will enable the evaluation of clinical response to chemotherapy, as well as identification of key cellular processes that change the activity of genes during therapy.

Keywords

• breast cancer
• neoadjuvant chemotherapy
• whole-transcriptome analysis
• tumor expression profile
• differential gene expression