The detection of microcalcifications in the breast by mammography is of great importance for the early diagnostics of breast cancer. This study aimed to establish the basic morphological and crystal-chemical properties of microscopic calcifications and their impact on breast cancer tissue. During the retrospective study, 55 out of 469 breast cancer samples had microcalcifications. The expression of the estrogen and progesterone receptors and Her2-neu showed no significant difference from the non-calcified samples. An in-depth study of 60 tumor samples revealed a higher expression of osteopontin in the calcified breast cancer samples (p ˂ 0.01). The mineral deposits had a hydroxyapatite composition. Within the group of calcified breast cancer samples, we detected six cases of colocalization of oxalate microcalcifications together with biominerals of the usual “hydroxyapatite” phase composition. The simultaneous presence of calcium oxalate and hydroxyapatite was accompanied by a different spatial localization of microcalcifications. Thus, the phase compositions of microcalcifications could not be used as criteria for the differential diagnostics of breast tumors.

Introduction Patients with lung cancer receive treatment according to National Cancer Comprehensive Network (NCCN) standards. However, disease recurrence is reported in about 30% of patients during the first five years. Our study aimed to establish independent predictors of lung cancer...

The global aging population has led to a growing incidence of malignancies, including metastatic non-small-cell lung cancer (mNSCLC). Immunosenescence may affect the efficacy of immune checkpoint inhibitors (ICIs). The prognostic role of age in ICI-treated mNSCLC remains uncertain. Objectives: This study aims to assess whether age independently influences survival, response, and toxicity in mNSCLC patients treated with ICIs, and to examine potential interactions with clinical factors. Methods: In this retrospective cohort study, 105 patients with mNSCLC treated with ICIs were enrolled. Patients were stratified into four groups based on age quartiles. Clinical, pathological, and treatment data were collected. Survival outcomes were analyzed using Kaplan–Meier curves, ROC curve and multivariable Cox regression models adjusted for confounders. Interaction and restricted cubic spline analyses were performed to explore age-related effects. The p < 0.05 was considered as statistically significant. Results: The median age was 60.8 years. Clinical benefit—defined as objective response rate (51.4%) and disease control rate (86.6%)—did not significantly differ across age quartiles (p = 0.551 and p = 0.257, respectively). Median overall survival also did not differ significantly (p = 0.2853). Cox regression and spline modeling demonstrated no independent association between chronological age and all-cause mortality (Model 3: HR = 1.00, 95% CI: 0.95–1.04, p = 0.889). However, interaction analyses revealed that poor ECOG performance status (p = 0.001), longer duration of ICI treatment (p < 0.0001), and low PD-L1 expression (p = 0.017) were stronger predictors of mortality in older patients. Age was associated with increased immune-related adverse events and higher Charlson Comorbidity Index scores, suggesting the need for age-specific management strategies. Conclusions: Age alone does not predict survival in mNSCLC patients receiving ICIs. However, functional status, treatment duration and PD-L1 expression may modify age-related outcomes.

Background. The association between body mass index and prognosis in patients with HER2-positive metastatic breast cancer (mBC) is unclear. Purpose – the first purpose of our study was to determine whether BMI is an independent prognostic factor for progression-free survival (PFS) and overall survival (OS) in HER2-positive mBC patients. The second objective was to assess the mutual impact of baseline clinicopathological characteristics on survival outcomes. Materials and Methods. The study group included patients treated at the Sumy Regional Clinical Oncology Center. We considered the underweight patients if their BMI was <18.5 kg/m2, normal weight 18.5–24.9 kg/m2, overweight 25.0–29.9 kg/m2, and obese ≥ 30 kg/m2. The following formula was used for calculations: weight/height2 (kilograms/meter2). Information about the height, weight, and other clinicopathological characteristics of the patient at the time of the start of drug therapy was taken from the primary medical documentation. Pearson’s test and Chi2 test for categorical variables were used to compare baseline clinicopathological characteristics in groups with normal, overweight, and obesity. The Kaplan-Meier method was used to establish the medians of PFS and OS. Cox regression analysis assessed the mutual impact on the survival of various clinicopathological characteristics. The statistical significance threshold was considered P ≤0.05. Results. Seventy-eight patients with HER2-positive mBC were enrolled and categorized according to their BMI in normal weight, overweight, and obese groups. BMI had a different impact on PFS and OS. Median PFS was 14.9, 11.9, and 14.2 months for normal-weight, overweight, and obese patients, respectively. There is no statistically significant difference in PFS between groups (Р = 0.110). Multivariable regression analysis confirmed no impact of BMI on PFS. Nevertheless, metastases in bones and kidneys and the nuclear grade were statistically significant determinants of PFS. Median OS was 26.4, 28.8, and 37.9 months for normal-weight, overweight, and obese patients, respectively. BMI, kidney metastases, and nuclear grade were prognostically significant determinants of OS. Conclusions. BMI is an independent prognostic factor of OS in patients with HER2-positive mBC. Obesity is associated with better OS but does not impact PFS. Metastases in bones and kidneys and the nuclear grade can predict survival outcomes.

Immune checkpoint inhibitors have opened up new possibilities in clinical oncology. Monoclonal antibodies have shown their high clinical efficiency. They block CTLA-4, PD-1, and PD-L1 receptors and activate the immune response. Many patients have stable and even complete responses. However, some patients have primary or acquired resistance. Therefore, the treatment results in this category of patients are not predictable. Mechanisms of resistance to immune checkpoint inhibitors have not been definitively studied. Many theories try to explain the mechanisms of this phenomenon. Our study aimed to structure and combine the data into groups depending on the etiological factor that reduces the immune response. In addition, based on understanding the mechanisms of resistance and the results of recent clinical studies, we aimed to identify the main ways to overcome it. Therefore, mechanisms that lead to resistance may be associated with tumor properties, tumor microenvironment, or patient characteristics. Tumor properties that reduce the immune response include a) low tumor mutation burden and loss of tumor neoantigens, b) changes in the processing or presentation of neoantigens, and c) changes in signaling pathways of tumor development and epigenetic modifications in genes. The tumor microenvironment is represented by stromal and immune cells, extracellular matrix, cytokines, and blood vessels. Each structure can enhance or reduce the immune response and contribute to the acquired resistance to immune checkpoint inhibitors. The effectiveness of the treatment depends not only on the cells in the tumor microenvironment but also on the metabolic background. In addition, the basic characteristics of the patient ( gender, gut microbiota, HLA-I genotype) can modify the immune response. Based on knowledge about the mechanisms of resistance to immune checkpoint inhibitors, several therapeutic strategies aimed at activating antitumor activity have been evaluated. All of them are based on combining immune checkpoint inhibitors with other drugs. One of the most common options is a combination of PD-1/PD-L1 and CTLA-4 inhibitors. Alternative immune checkpoints are TIM-3, LAG-3, TIGIT and VISTA. Combining immunotherapy with chemotherapy, targeted therapy, neoangiogenesis inhibitors, epigenetic modifiers, PARP or TGF-β inhibitors enhances antitumor response by preventing depletion of effector T cells, enhancing T cell infiltration in the tumor, changes on the tumor microenvironment, and decreasing the accumulation of immunosuppressive cells. This review explores the biological mechanisms of resistance and potential ways of solving this problem.