Cardio-oncology最新文献

Cardiovascular disease is the prevailing cause of death among cancer survivors. Remarkable increase in cardiac disease burden in this group is likely due to the effects of cancer itself and, especially, cardiotoxic cancer treatments. Of the cardiotoxic cancer treatments, anthracyclines are notoriously known for causing vascular damage and severe cardiovascular complications. A defining feature of cardiac damage by doxorubicin (Dox), a prototypical anthracycline, is that it typically progresses after completion of chemotherapy. As the nature of delayed deterioration is not understood, we focused in this study on the events that occur upon completion of chemotherapy. We adopted the Dox treatment/washout model to examine its lasting effects on endothelial cells. Our ChIP sequencing, transcriptomic, reporter plasmid, and Smad2/3 phosphorylation experiments demonstrated enhanced activity of the canonical TGF-β and activin pathways during Dox washout. Another notable feature was sustained mesenchymal reprogramming with significant upregulation of transcripts characteristic of fibroblastic and smooth muscle lineages, both in endothelial cultures and cardiac microvascular endothelial cells in vivo. We utilized a selective ALK4/5/7 receptor kinase inhibitor, SB431542 (SB), to probe the role of the canonical TGF-β/activin pathways in endothelial-to-mesenchymal reprogramming by Dox. When present during Dox washout, SB blocked increased expression of both mesenchymal transcripts and protein markers, and prevented cytoskeletal changes and fibronectin production by the treated endothelial cells. Cytoskeletal rearrangements led to increased endothelial monolayer permeability that was abolished by SB treatment. Thus, increased production of ALK4/5 receptor ligands, TGF-β2 and activin, and heightened Smad2/3 activation response to these ligands during Dox washout leads to sustained mesenchymal reprogramming of endothelial cells and compromised endothelial barrier function.

Background: Breast cancer is the most common malignancy among women globally and the second most frequently diagnosed cancer overall, with 2.3 million new cases reported in 2022. While advances in therapy have substantially improved survival, cardiovascular disease (CVD) has emerged as the leading cause of non-cancer mortality in this population. Real-world evidence on the incidence and trajectory of heart failure (HF) and treatment-related cardiotoxicity remains limited, with existing studies often constrained by small sample sizes or narrow therapeutic focus. This scoping review aimed to synthesise evidence on the incidence of HF, cardiovascular mortality, and all-cause mortality in individuals with breast cancer, map additional cardiovascular outcomes, and identify high-risk subgroups.

Methods: The review followed the Joanna Briggs Institute methodology, applying the Participant-Concept-Context framework to identify eligible studies. Inclusion criteria comprised peer-reviewed, observational studies in English published up to July 2024 that reported HF incidence in breast cancer patients; clinical trials, reviews, and prevalence studies were excluded. Comprehensive searches of PubMed, MEDLINE, CINAHL, and Embase were undertaken, with independent dual screening. Data were synthesised descriptively and thematically, and study quality was assessed using the CASP tool.

Results: Fifteen population-based cohort studies were included, with sample sizes ranging from 294 to 122,217 and follow-up durations of 3 to 19 years. Most cohorts included women with early-stage (I-III) disease and displayed heterogeneity in demographics, comorbidities, and treatments. Hypertension, diabetes, and dyslipidaemia were the most common comorbidities. Chemotherapy and radiotherapy were administered in up to 58% and 78.5% of patients, respectively. HF risk was significantly elevated (hazard ratios [HRs] up to 2.71), peaking within the first-year post-diagnosis and persisting for up to 17 years. All-cause mortality was consistently higher than in non-cancer controls (HRs > 3.0), whereas cardiovascular mortality findings were mixed. Younger age, cardiometabolic comorbidities, advanced cancer stage, and exposure to anthracyclines (HR 1.74) or trastuzumab (HR 2.34) were key risk factors. Additional cardiovascular outcomes-including ischaemic heart disease, atrial fibrillation, stroke, and thromboembolism-were frequently observed, particularly in early survivorship. Most studies were rated as high quality.

Conclusion: Breast cancer survivors face a substantial and sustained cardiovascular burden, particularly for HF and all-cause mortality. These findings emphasise the need for early CVD risk assessment, targeted cardioprotective interventions, and long-term surveillance. Large, prospective studies are essential to inform precision cardio-oncology and optimise survivorship outcomes.