[Increased activity of inflammation-related signaling pathways in anthracycline- paclitaxel resistant breast carcinomas].

Abstract

A frequently recommended systemic therapy for breast cancer involves a combination of anthracyclines and taxanes, however, approximately 30% of patients experience recurrence. We aimed to investigate the mechanisms of resistance to anthracycline-paclitaxel based treatment by analyzing gene expression patterns in tumor samples collected during surgery and subsequent therapeutic responses. A database of 187 patients with information about relapse-free survival (RFS) allowed the analysis of 10,017 genes. Patients were divided into responders and nonresponders based on whether relapse occurred within sixty months. The expression of each gene was compared between the two groups using the Mann-Whitney U-test, with a statistical significance set at p <0.05 and fold change (FC) ≥1.44. We identified 51 up-regulated genes among nonresponders, primarily associated with inflammatory processes and the innate immune response. The high expression of SLC7A5, encoding an amino acid transporter, was linked to worse overall survival (p = 2.3E-10), with elevated expression in tumors (p = 2.94E-20), and further increase in metastases (p = 1.33E-10). Our results emphasize the significance of tumor microenvironment and metabolism in therapy resistance. These findings may allow better patient classification and identification of relevant treatment targets.