The introduction in clinical practice of selective cyclin-dependent kinase (CDK) 4/6 inhibitors improves the outcome of patients with hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC). In Romania, the three available CDK 4/6 inhibitors (Palbociclib, Ribociclib and Ademaciclib) have been approved by the National Agency for Medicines (ANM) in 2019, 2020 and 2021. We conducted a retrospective study from 2019 to 2022 on 107 patients with metastatic breast cancer HR+ that have been treated with CDK 4/6 inhibitors in addition to hormone therapy in the Oncology Department of Colțea Clinical Hospital in Bucharest. The purpose of this study is to calculate the median progression-free survival (PFS) and to compare it with the median PFS from other randomized clinical trials. A key difference from other studies is that our study evaluated both patients with non-visceral mBC and patients with visceral mBC, as these two groups often have different outcomes. A total of 79.4% were postmenopausal patients and 20.6% were premenopausal; 42.1% had different stages at the beginning of disease and 57.9% presented newly metastatic disease. Median PFS was 17 months, unlike randomized clinical trials which reported a median PFS of 25.3 months. The combination of CDK 4/6 inhibitors with endocrine therapy is the golden standard treatment in HR-positive, HER2-negative metastatic breast cancer, bringing a prolongation of survival for these patients. Our results show no major differences compared to randomized clinical trials, despite the smaller patient group. In order to have a picture of the efficacy of the treatment as close as possible to the real-world data, we believe that it would be very useful to have a collaboration between several oncology departments in different institutions to carry out a multi-center study on large groups of patients.

This review explores the interconnection between precursor lesions of breast cancer (typical ductal hyperplasia, atypical ductal/lobular hyperplasia) and the subclinical of multiple organ failure syndrome, both representing early stages marked by alterations preceding clinical symptoms, undetectable through conventional diagnostic methods. Addressing the question “Why patients with breast cancer exhibit a tendency to deteriorate”, this study investigates the biological progression from a subclinical multiple organ failure syndrome, characterized by insidious but indisputable lesions, to an acute (clinical) state resembling a cascade akin to a waterfall or domino effect, often culminating in the patient’s demise. A comprehensive literature search was conducted using PubMed, Google Scholar, and Scopus databases in October 2023, employing keywords such as “MODS”, “SIRS”, “sepsis”, “pathophysiology of MODS”, “MODS in cancer patients”, “multiple organ failure”, “risk factors”, “cancer”, “ICU”, “quality of life”, and “breast cancer”. Supplementary references were extracted from the retrieved articles. This study emphasizes the importance of early identification and prevention of the multiple organ failure cascade at the inception of the malignant state, aiming to enhance the quality of life and extend survival. This pursuit contributes to a deeper understanding of risk factors and viable therapeutic options. Despite the existence of the subclinical multiple organ failure syndrome, current diagnostic methodologies remain inadequate, prompting consideration of AI as an increasingly crucial tool for early identification in the diagnostic process.

Breast cancer (BC) significantly impacts the quality of life (QoL) of affected individuals. This study, conducted at Colțea Clinical Hospital, Bucharest, aimed to assess the impact of organ failures and metastases on QoL in breast cancer patients using EORTC QLQ-C30 and EORTC QLQ-BR45 questionnaires and the survival rate to understand the clinical journey and the quality of life status in breast cancer patients. From January 2019 to October 2022, a prospective, observational study surveyed 874 patients, revealing 201 fatalities, 66 refusals, and 607 eligible participants. Results indicated statistically significant differences in various QoL aspects for patients experiencing heart failure, including physical functioning, pain, insomnia, global health status, and overall summary score. Kidney failure exhibited significance in physical functioning for QLQ-C30 and body image, sexual functioning, and endocrine sexual symptoms for QLQ-BR45. Respiratory failure demonstrated significant differences across multiple QoL domains. Patients with bone metastases reported lower physical functioning (p = 0.006) and increased pain (p = 0.002). This study has revealed an overall 5-year life expectancy of 68.8%, with survival rates of 93.8% for Stage I, 86.3% for Stage II, and 77.2% for Stage III breast cancer. Metastatic cancer patients have shown a 35.6% survival rate over 45 months, with a median survival duration of 36 months. A significant limitation of our study was the administration of the questionnaire only once, preventing us from quantifying the impact of specific treatment types on quality of life. This study emphasizes the necessity of using standardized QoL assessments in clinical practice from the initial presentation to ongoing follow-up.

Background: Immunotherapy with immune checkpoint inhibitors (ICIs) has fundamentally transformed cancer treatments. Unfortunately, its benefits are accompanied by the occurrence of immune-related adverse events (irAEs). While non-cardiac irAEs have been consistently associated with a favorable prognosis, the impact of cardiac toxicities remains insufficiently explored. Methods: We conducted a retrospective, observational study at the Oncology Department of Colțea Clinical Hospital, Bucharest. All the patients treated with ICIs between 1 May 2019 and 1 February 2024 were selected in the initial cohort. Of 512 eligible patients, 435 were included in the final analysis, with comprehensive recordings of clinical, oncological, and cardiac monitoring parameters, and at least one complete cycle of ICI treatment. Adverse events were classified according to CTCAE v5.0, and overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier estimates and Cox regression models. Results: Our results showed that patients who developed non-cardiac irAEs experienced a significant survival benefit: median OS 26.0 months (95% CI, 15.5–NA) vs. 13.9 months (95% CI, 12.4–16.5), 0.66 (95% CI, 0.49–0.9) hazard ratio (HR); median PFS 12.3 months (95% CI, 8.1–26.0) vs. 8.7 months (95% CI, 7.3–10.3), 0.74 (95% CI, 0.56–0.97) HR. Conversely, patients with cardiac toxicities did not derive the same advantage, with similar OS and PFS values that did not reach statistical significance: median OS 15.0 months (95% CI, 13.3–19.3) vs. 15.8 months (95% CI, 12.0–30.3), 1.11 (95% CI, 0.78–1.57) HR; median PFS 9.1 months (95% CI, 7.6–10.4) vs. 8.1 months (95% CI, 5.3–19.3), 1.003 (95% CI, 0.72–1.39) HR. Conclusions: These findings support the role of non-cardiac irAEs as markers of favorable therapeutic response, while cardiac irAEs do not confer the same prognostic benefit. The results underscore the importance of active cardiovascular monitoring and close multidisciplinary collaboration in the management of patients receiving ICIs.

Background/Objectives: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), including cardiac toxicities, which may have significant clinical impact. Data regarding predictors of immune-mediated cardiac toxicity remain limited. The aim of this study was to evaluate the association between cardiovascular comorbidities and the development of cardiac irAEs, as well as to assess their potential role in predicting non-cardiac irAEs. Methods: We conducted a retrospective observational study including oncological patients treated with immune checkpoint inhibitors at Colțea Clinical Hospital. Patients with complete clinical data and documented cardiac and non-cardiac irAEs were included. Demographic characteristics, prior oncological treatments, cardiovascular comorbidities, and relevant clinical parameters were analyzed. Univariate and multivariate logistic regression analyses were performed to identify predictors of immune-related adverse events. Results: Hypercholesterolemia, atrial fibrillation, history of acute coronary syndrome, and heart failure were significantly associated with the development of cardiac irAEs. In multivariate analysis, hypercholesterolemia and pre-existing cardiovascular disease remained independent predictors of cardiac toxicity. No significant association was observed between non-cardiac irAEs and cardiac irAEs. The predictive model demonstrated high specificity but moderate sensitivity. Conclusions: Cardiovascular comorbidities play a significant role in the development of immune-related cardiac toxicities. Identification of these risk factors may improve patient stratification and support individualized monitoring strategies in patients receiving immune checkpoint inhibitors.

Since the first approval of CTLA-4 blockade for melanoma, immune checkpoint inhibitors (ICIs) have expanded into a major class of cancer therapy, with more than 100 FDA-approved oncological indications across metastatic and earlier-stage disease settings, including use as monotherapy and in combination regimens. Preclinical research has largely focused on myocarditis and atherosclerosis, but a wider set of phenotypes, such as non-inflammatory left ventricular dysfunction (NILVD), arrhythmias, and vasculitis, can be observed, and they are rarely connected within a single mechanistic model. We aim to build a systems-oriented, mechanistic framework of the most widely studied biological processes; it will link the main checkpoint pathways to relevant cardiac and vascular cell types, molecular pathways, immune synapses, and candidate biomarkers. We searched PubMed, Scopus, and Web of Science using combinations of terms for immune checkpoint inhibition and cardiovascular-immune-related adverse events that provide mechanistic insight into cardiac-immune-related adverse reactions (irAEs). An AI-assisted semantic clustering approach was used only to organize the included literature. The integrated framework identifies PD-1/PD-L1 as the dominant mechanistic hub linking T-cell activation, endothelial recruitment, myocardial injury, and vascular inflammation. Across phenotypes, a shared immune core involving checkpoint pathways, cytokine signaling, and leukocyte trafficking coexists with phenotype-restricted mediators that may bias injury toward myocarditis, vascular inflammation, conduction-system disease, or NILVD. KEGG analyses support the enrichment of T-cell receptor signaling, Th17 differentiation, JAK-STAT signaling, cytokine–cytokine receptor interaction, and lipid and atherosclerosis pathways. Candidate biomarkers emerging from the reviewed literature include troponin, IL-6, CXCL9/CXCL10/CXCL13, S100A family proteins, ROCK2, HLA-linked susceptibility signals, and T-cell receptor clonality markers. The AI-assisted clustering broadly recapitulated the expert-defined thematic structure while identifying finer semantic neighborhoods within the literature. This framework provides a support map for further hypotheses about toxicity patterns with current and next-generation checkpoint strategies on the cardiac system, while AI-assisted clustering provides a complementary method for organizing the literature rather than an independent source of biological inference.