MOLECULAR-GENETIC MARKERS OF RESPONSE TO NEOADJUVANT CHEMOTHERAPY WITH ANTHRACYCLINES IN BREAST CANCER PATIENTS

Abstract

The purpose of the study: to evaluate the response to neoadjuvant anthracycline-based chemotherapy depending on the presence of deletions and amplifications of different chromosomal loci and the expression level of topoisomerase 2а in tumor tissue of breast cancer patients. Materials and methods. The study included 46 patients with stage T2–4N0–3M0 breast cancer, who received 2–6 cycles of neoadjuvant chemotherapy with FAC and CAX regimens. Results. The relationship between the expression level of Тор2а>5, deletions of ABCB1, ABCB3, 18р11.21, 11q22.1 loci and amplification of 1q24.1-43 and the response to preoperative treatment was found. Of the 34 patients having at least one of these markers in the tumor tissue, 85.3 % of them demonstrated partial response to neoadjuvant chemotherapy (> 50 % reduction of tumor) and 14.7 % had stable disease and disease progression. No above markers were found in the tumor tissue of 12 patients, who did not respond to preoperative treatment. Conclusion. High levels of Тор2а>5 expression, deletions of ABCB1; ABCB3; 18р11.21; 11q22.1 loci and 1q24.1-43 amplification were shown to be predictive markers of response to neoadjuvant anthracycline-based chemotherapy. The presence of at least one of these markers allowed us to predict response to preoperative treatment in 85 % of cases.

Keywords

• breast cancer
• neoadjuvant chemotherapy
• predictive markers
• level of тор2а>5 expression
• deletion of abc-transporter genes
• dna copy number variations