Expression of excision repair genes in breast tumors during neoadjuvant chemotherapy

The main anticancer drugs (particularly anthracyclines and taxanes) widely used in neoadjuvant breast cancer therapy can cause DNA damage in tumor cells. Activation of excision repair systems in these cells can reduce treatment effectiveness, promoting damage repair and the development of resistance. Therefore, studying the expression level of excision repair genes is a promising approach for identifying potential predictive markers of treatment efficacy and potential prognostic markers of hematogenous metastasis. this study assessed changes in the expression level of excision repair genes in luminal B HER2-subtype breast tumors during treatment with standard neoadjuvant chemotherapy regimens.

Material and Methods. Paired biopsy samples (pre-treatment and post-NAC tumor tissue) from each patient were used. The tumor expression landscape was assessed using full-transcriptome microarray analysis with Clariom™ S Assay, human microarrays (Affymetrix, USA).

Results. A study assessing the excision repair gene expression in breast tumors before therapy with anthracycline-containing regimens found that the expression levels of 3 genes (DDB1, FAN1, GTF2H3) changed significantly depending on how the patients responded to neoadjuvant chemotherapy. Before treatment with taxane-containing regimens, 5 genes CDK2AP2, MMS19, DDB1, CCNL2, TDG showed significant changes. The assessment of the excision repair gene expression in breast tumors after therapy with anthracycline-containing regimens found that the expression levels of 5 genes (RFC1, RAD23B, CCNH, POLB, RPA4) changed significantly depending on hematogenous metastasis status. After therapy with taxane-containing regimens, 7 genes (PARP1, NTHL1, ERCC8, XAB2, DUT, CCNL2, MNAT1) showed significant changes. Analysis of metastasis-free survival of patients revealed statistically significant changes in the expression levels of NTHL1, XAB2 and DUT genes in the tumor after taxane-containing treatment.

Conclusion. Potential gene expression markers for predicting hematogenous metastasis of HER2-negative breast tumors treated with taxane-containing NAC regimens were identified.

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