NEOADJUVANT CHEMOTHERAPY FOR HEREDITARY BREAST CANCER

This article presents the immediate results of neoadjuvant systemic cytotoxic therapy in patients with hereditary breast cancer

Material and methods. In our study, a comparative analysis of the efficacy of non-adjuvant polychemotherapy in
accordance with the molecular biological characteristics of 266 patients with locally advanced breast cancer T2-3N1-2M0
was performed in 45 of which the tumor was associated with a mutation in the BRCA1, CHEK2 or BLM genes.
Results. The complete pathological response in the group of hereditary breast cancer was achieved more often than in the control group in a comparative evaluation of the immediate results of neoadjuvant chemotherapy, 17,8% vs 8,6% (p=0,04). The complete pathological response was recorded with presence of germinal mutations of BRCA1 genes at 34,1%, BLM с. 1642С>T (Q548X) in 20% and did not occur in patients with CHEK2 1100delC. The incidence of complete pathological response in the group of triple negative breast cancer with the «founder mutation» was higher in comparison with the control group – 26,1% vs 7,8% (p=0,01). Among patients with BRCA1 5382insC-associated triple negative breast cancer the greatest efficacy was observed after anthracyclinecontaining neoadjuvant chemotherapy compared with taxane-containing chemotherapy (pCR=57,1% vs 9,1% (p=0,04)). A high incidence of the general objective response (OR) to neoadjuvant endocrine therapy with aromatase inhibitors in comparison with cytotoxic therapy was identified in patients with luminal A breast cancer (80% vs 40,6% (p=0,001)). The magnitude of the overall objective response (OR) after neoadjuvant chemotherapy was higher in patients with BRCA1/ CHECK2/ BLM-associated luminal A breast cancer compared with sporadic breast cancer – 58,8% vs 34% (p=0,048).
Conclusions. Hereditary breast cancer is overwhelmingly associated with BRCA1 5382insC mutation. The predictive value for neoadjuvant chemotherapy of triplе negative and luminal A breast cancer had mutations in the BRCA1 gene. A marker of high sensitivity to anthracyclinecontaining neoadjuvant chemotherapy in comparison with taxanecontaining regimens in patients with triple negative breast cancer is the mutation BRCA1 5382insC.