EVALUATION OF THE TUMOR PROLIFERATIVE ACTIVITY INDEX PCNA IN A VARIETY OF ROUTES OF DELIVERY OF CHEMOTHERAPEUTIC DRUGS IN PATIENTS WITH LOCALLY ADVANCED BREAST CANCER

Abstract

Introduction. Breast cancer is one of the most live issue of the modern oncology, as it holds the leading position among the causes of female mortality and disability. A special place in the structure of this pathology is occupied by locally advanced forms of malignant tumor in which the effectiveness of the treatments used is unfortunately very low, therefore the prognosis is rather unfavorable. This determines there levance of them search for new methods of diagnosis and treatment in such patients. In the context of this research, we identified the role of neoadjuvant selective intra-arterial polychemotherapy in adverse primary inoperable forms of breast cancer. To determine and predict the effectiveness of this treatment, we used tumor proliferative activity. The research examined the expression of a PCNA nuclear proliferation marker for prognostic and diagnostic evaluation in the light of unsatisfactory literature on the subject in the context of determining similar parameters by other criteria. PCNA level was taken as the main dichotomous point of prognostic assessment of neoadjuvant therapy based on the results of retrospective analysis of the efficacy of preoperative treatment and determination of statistically significant difference between the results in the subgroups with lower and higher marker levels, which in our study were divided according to the median value of the immunohistochemical parameter level in the total sample of 25 %. Objective. Evaluation of the effectiveness of neoadjuvant treatment using systemic and selective intraarterial routes of chemotherapy administration in patients with locally advanced breast cancer using the tumor proliferative index based on the PCNA marker. Materials and methods. A retrospective analysis of the results of a comprehensive treatment of patients with initially inoperable locally advanced breast cancer based on selective and systemic routes of administration of chemotherapy was performed. The study included 63 patients. The sample was divided into 2groups depending on the selected type of neoadjuvant polychemotherapy: 1st group – control group were formed (based on systemic therapy) and 2nd group – study group (the selective intraarterial delivery route was used). The control group consisted of 22 patients, the study – 41 patients. All patients revealed stage IIIb of the disease. In accordance with the clinical manifestations, the patients were distributed as follows: control group include 12 patients with сT4bN1M0, 6 patients with сT4aN1M0 and 4 patients with сT4cN1M0; study group include 23 patients with сT4bN1M0, 7 patients with сT4aN1M0 and 11 patients with сT4cN1M0. All patients included in the study had luminal type B. In parallel with routine methods, the dynamics of proliferative activity of the tumor by the PCNA nuclear antigen was additionally studied in all patients. This study demonstrates the level of the PCNA marker at the start of treatment and after the completion of polychemotherapy (PCT). After PCT, all patients underwent surgical intervention. Taking into account the pathological examination, the patients were reassigned as follows: in the control group, 4 patients has pT4aN0M0, 2 patients – pT4aN1M0, 4 patients – pT4bN0M0, 8 patients – pT4bN1M0, 1 patient – pT4cN0M0 and 3 patients – pT4cN1M0; in the study group, 3 patients has PT4aN1M0, 4 patients – PT4aN0M0, 15 patients – PT4bN1M0, 8 patients – PT4bN0M0, 6 patients – PT4cN1M0 and 5 patients – PT4cN0M0. Since the patients belonged to the group with Luminal type of tumor, each of them received hormone therapy in an adjuvant regimen. Patients of reproductive age were treated with the group of estrogen antagonists, while postmenopausal patients received aromatase inhibitors. Targeted therapy was not used in the study. A statistical analysis was performed between the comparison groups; the median marker level in 25 % was taken as the critical value. Results. According to the degree of PCNA regression, it was determined that selective intra-arterial chemotherapy for breast cancer with a low proliferative activity index has a statistical advantage in overall survival and average life expectancy (p < 0.05) compared with control group. Conclusions. Using the PCNA indicator, one can reliably evaluate the proliferative activity of the tumor, thus predicting the effect of neoadjuvant chemotherapy and choosing the optimal tactics of complex treatment. Keywords: locally advanced breast cancer, proliferative activity index, marker of nuclear antigen of proliferating cells, systemic polychemotherapy, selective intra-arterial polychemotherapy.