[Alterations in the transcriptional profile of genes in tumors as a prerequisite for personalization of treatment in breast cancer patients].

OBJECTIVE

To evaluate changes in gene expression activity during preoperative testing for tumor hormone sensitivity to aromatase inhibitors and tamoxifen in postmenopausal women with ESR+/HER2- breast cancer.

MATERIAL AND

METHODS

The study included 174 breast cancer patients. Pathological examination of FFPE core biopsy specimens, performed before the hormone response test, and surgical specimens were examined, as well as immunohistochemistry (Ki67, ER, PR, HER2/neu) and molecular genetic testing of an expression panel of 45 target genes using quantitative real-time PCR.

RESULTS

The use of aromatase inhibitors in the preoperative hormone response test is accompanied by statistically significant changes in the mRNA expression of 37 genes in breast tumors, of which a decrease in the expression level was found for 35 genes (ESR1, PGR, AR, ERBB2, FGFR4, MKI67, MYBL2, CCNB1, AURKA, BIRC5, CCND1, CCNE1, CDKN2A, KIF14, PPP2R2A, PTTG1, TMEM45B, TPX2, ANLN, MMP11, CTSL2, EMSY, PAK1, BCL2, BAG1, PTEN, TYMS, EXO1, UBE2T, NAT1, SCGB2A2, GATA3, FOXA1, ZNF703, CD274/PD-L1), an increase - for two genes (SFRP1, KRT5). While the use of tamoxifen statistically significantly correlates with a decrease in the level of mRNA expression of 35 genes: ESR1, PGR, AR, EGFR, ERBB2, FGFR4, MKI67, MYBL2, CCNB1, AURKA, BIRC5, CCND1, CCNE1, CDKN2A, KIF14, PPP2R2A, PTTG1, TMEM45A, TMEM45B, TPX2, ANLN, MMP11, EMSY, PAK1, BCL2, BAG1, PTEN, TYMS, EXO1, UBE2T, NAT1, GATA3, FOXA1, ZNF703, CD274/PD-L1, and an increase in only one gene - MYC.

CONCLUSION

Comparative mRNA expression analysis confirms that a short preoperative course of aromatase inhibitors induces a more potent and uniform molecular response, characterized by profound suppression of proliferation and complete inhibition of estrogen-dependent signaling. Tamoxifen therapy is also effective but results in less pronounced suppression of key targets and, crucially, may be accompanied by early activation of the MYC oncogene, a potential marker for resistance development.