Comparison of Clinical, Histological and Molecular Features of Primary Operable Breast Cancer in Patients from Kosovar and Croatian University Hospitals

Background The aim of this study was to explore the clinical, patohistological and molecular characteristics of primary operable breast cancer in patients from Croatia and Kosovo, in order to compare disease stage at the time of diagnosis, in country with implemented mammography screening and early diagnostic methods with country without it. Methods The study prospectively included 213 female patients with breast cancer (BC) ranging from 28 to 87 years of age, from which 100 from Kosovo and 113 from Croatia. Age and menopausal status of the patients were recorded before surgery. Subsequent to surgery, histopathology and immunohistochemistry analysis was carried out and data were statistically analysed. Categorical variables were compared using chi-square analysis and presented as frequencies and percentages. For non-parametric data, Mann-Whitney U test was used in order to compare means of two independent groups. A value of P < 0.05 was considered statistically significant. Results There were larger tumors, more patients with metastatic axillary lymph nodes and more stage III patients in Kosovo cohort. In addition, the rate of lympho-vascular invasion (LVI) and the expression of progesteron receptor (PR) were significantly higher in Kosovar patients. The other histological and immunohistochemical features were not found to be any different in the two cohorts. Conclusions The results of this study from two university hospitals from Croatia and Kosovo demonstrate that the BC patients in Kosovo have more advanced stage of disease at the time of diagnosis compared to Croatia.

AGE-RELATED FEATURES OF SYSTEMIC ANTITUMOR IMMUNE RESPONSE IN PATIENTS WITH PRIMARY OPERABLE BREAST CANCER AND CANCER OF THE ORAL MUCOSA

Introduction. Age is considered as an important clinical and pathological factor in cancer patients. Malignant tumors are more likely to develop in older people, but the disease is less aggressive than in young patients. According to various authors, the influence of age on the development of tumors largely depends on the age-related features of the immune system.The aim of the present study was to determine the relationship of indicators of systemic antitumor immune response with the age of patients with primary operable breast cancer and cancer of the oral mucosa.Materials and methods. The study included patients with all subtypes of primary-operable breast cancer (n = 145) and patients with cancer of the oral mucosa (n = 29). Immunophenotyping of peripheral blood lymphocytes was performed using a wide panel of monoclonal antibodies to markers of adaptive and innate immunity cells.Results. In elder patients (40 years and older) with primary-operable breast cancer, the percentage of activated CD25+ lymphocytes and CD4+CD25+ and CD3+CD4+ T cells, NKT cells, activated HLA-DR+ lymphocytes, including activated CD3+HLA-DR+ T cells before treatment, was statistically significantly higher than in patients younger than 40 years. Patients of this group showed increase of CD8+CD - 11b+CD28– CTLs and a decrease in the number of naive lymphocytes (CD4 – CD62L+ and CD8+CD11b – CD28+) in comparison with control percentage, and the downward trend in CD4+CD25+CD127– Treg, with increased numbers of CD4+CD25+ T cells. In patients with cancer of the oral mucosa, an increase in the number of cells of some populations of the immune effector link and a decrease in the number of suppressor lymphocytes were revealed with age.Conclusion. The results suggest that age-related differences in the state of systemic antitumor immune response contribute to a more favorable course of breast cancer and some other malignancies in older persons. It is obvious that the features of age differences in the immune response to the tumor should be taken into account when prescribing systemic therapy, including immunotherapy.All patients gave written informed consent to participate in the study

Primary operable breast cancer: molecular subtypes and morphological prognostic factors

Aim. To study the immediate and long - term results of treatment of patients with a primary operable breast cancer, depending on the morphological and biological characteristics of the tumor. Materials and methods. The retrospective study included 974 patients aged from 30 to 82 years (a mean age of54.5 years) with a primary operable breast cancer (T1-2N0-1M0) observed from 2005 to 2012. The overall survival (OS) and disease - free survival (DFS) were studied depending on the histological type, molecular - biological subtype of breast cancer, axillary status, lymphovascular invasion, tumor histologic grade, proliferation index (by Ki-67 staining) and HER2 protein expression. Statistical data processing included a comparison of the frequencies of the studied traits, analysis of survival curves by the Kaplan-Meier method.Results. Indicators of a 5-year OS and 5 and 10-year OS and DFS were lower in carcinomas of mixed type compared with invasive carcinoma of no special type ( p =0.03) and invasive lobular carcinoma ( p =0.01). In the absence of metastases in regional lymph nodes, indicators of 5 and 10-year OS were higher compared with the macrometastatic involvement of one ( p =0.02) or two or more lymph nodes ( p =0.004): 96.0% and 89.3%; 95.4% and 79.0%; 88.9% and 79.3%, respectively. A similar trend has been noted for indicators of 5 and 10-year DFS. The OS in the absence of metastases in the lymph nodes was greater with the luminal B HER2-positive subtype and triple - negative breast cancer. The degree of malignancy of the tumor had no effect on OS. The probability of disease recurrence was significantly higher in patients with a degree of G3 compared with G1 ( p =0.00001) and G2 ( p =0.002): the rates of 5 and 10-year - old DFS were: 84.8 and 55.0%; 94.1 and 86.0%; 88.9 and 72.2%, respectively. The expression of HER2 and Ki-67 proliferation index influenced the DFS without affecting the OS.Conclusions. The morphological factors deteriorating the OS and DFS of patients with primary operable breast cancer are the presence of macrometastases in regional lymph nodes, the defeat of two or more lymph nodes, the presence of lymphovascular invasion, mixed histological form of breast cancer. The subtypes with a more aggressive course include: HER2-positive tumors, triple negative breast cancer.

Correlation between TopIIα and ki-67 expression in tumors of luminal, primary operable breast cancer without HER2/neu overexpression in postmenopausal women as a prognostic factor.

e12065 Background: Assessment of proliferative activity is important in terms of tumor prognosis. Topoisomerase IIα (TopIIα) and ki-67 are common markers of breast cancer (BC) cell proliferation. The purpose of the study was to assess the correlation between TopIIα and ki-67 expression as a prognostic factor in luminal, primary operable breast cancer without Her 2 neu overexpression in postmenopausal women. Methods: 60 postmenopausal patients with BC (invasive ductal carcinoma) were equally divided into 3 groups: I –luminal A BC, surgical treatment with subsequent radiotherapy and hormonal therapy; II – luminal B BC, surgical treatment with subsequent radiotherapy and hormonal therapy; III – luminal B BC, surgical treatment with subsequent radiotherapy, polychemotherapy and hormonal therapy. Mean age of patients: I – 76.16±3.14 years, II – 65.0±3.91, III – 74.0±2.54 years. Immunohistochemical study was performed with mouse monoclonal ki-67 (Thermo scientific) and TopIIα (Santa Cruz Biotechnology) antibodies using the Reveal Polyvalent HRP-DAB Detection System. Results were analyzed using the STATISTICA 10.0 program (StatSoftInc., USA). Results: The average expression levels of the ki-67 marker in the groups were: I - 12.3±1.4%, II - 15.1±3.1%, III - 37.0±7.1%; TopIIα expression – 3.5±1.6%, 16.0±5.9%, 21.7±6.4%, respectively. The statistically significant Spearman correlation between TopIIα and ki-67 was observed both as general in groups (r = 0.787 at p < 0.001) and in groups with luminal B subtype (groups II and III). Strong positive correlation between TopIIα and ki-67 was registered in groups II (r = 0.941 at p < 0.01) and III (r = 0.864 at p < 0.001) with luminal B subtype. Weak correlation was observed in group I with luminal A subtype (r = 0.477 at p≥0.05). Conclusions: The study revealed a correlative increase in the level of TopIIα with simultaneous overexpression of the ki-67 protein in the studied groups. This indicator can be considered predictive for breast cancer.

The modern trends in diagnosis and treatment of primary operable breast cancer

The article considers the modern methods of diagnosis and treatment of primary operable breast cancer depending on molecular biological profile of the tumor.