Biomolecules & biomedicine最新文献

{"title":"Development and internal validation of prognostic nomograms for overall and breast cancer-specific survival in de novo stage IV HER2-positive breast cancer.","authors":"Xiaojie Yu, Deyuan Fu, Longdi Yao","doi":"10.17305/bb.2026.14655","DOIUrl":"https://doi.org/10.17305/bb.2026.14655","url":null,"abstract":"<p><p>The widespread adoption of contemporary human epidermal growth factor receptor 2 (HER2)-targeted therapies has altered survival in HER2-positive metastatic breast cancer, potentially limiting the applicability of older prognostic models. We aimed to develop and internally validate nomograms for overall survival (OS) and breast cancer-specific survival (BCSS) in patients with de novo stage IV HER2-positive breast cancer diagnosed during 2018-2021. Using the Surveillance, Epidemiology, and End Results (SEER) database, 1,516 patients were randomly assigned to training (n = 1,061) and internal hold-out validation (n = 455) cohorts. Random Survival Forest analysis with a 98% out-of-bag concordance index criterion selected variables for multivariable Cox regression models predicting 1-, 3-, and 5-year survival. Discrimination, calibration, clinical utility, and risk stratification were assessed. Nine variables were retained for OS and seven for BCSS. Concordance indices in the training and validation cohorts were 0.764 and 0.741 for OS and 0.747 and 0.736 for BCSS, respectively. Areas under the time-dependent receiver operating characteristic curves (AUCs) ranged from 0.73 to 0.82. Calibration was generally acceptable, and decision curve analysis suggested potential net clinical benefit. High-risk patients had markedly poorer OS (hazard ratios, 5.05 in training and 5.07 in validation) and BCSS (4.32 and 4.09, respectively; all p < 0.001). Sensitivity analyses addressing the time-varying chemotherapy effect and competing risks broadly supported the primary findings. The nomograms showed good internal discrimination and may support individualized prognostic assessment once initial treatment information is available. However, SEER does not record specific HER2-targeted regimens; therefore, this cohort represents a contemporary calendar period rather than a treatment-confirmed dual-HER2-blockade population. External validation in treatment-annotated cohorts is required, and 5-year estimates should be interpreted cautiously given the median follow-up of 27 months.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of general versus spinal anesthesia with perioperative changes in serum neuron-specific enolase, adiponectin, and visinin-like protein-1.","authors":"Oguzhan Cucu, Ergun Gunduz, Hafize Uzun, Naile Fevziye Misirlioglu, Bagnu Dundar, Seza Apiliogullari","doi":"10.17305/bb.2026.14652","DOIUrl":"https://doi.org/10.17305/bb.2026.14652","url":null,"abstract":"<p><p>Anesthesia and surgical stress may produce distinct neuronal and metabolic responses, but comparative data on perioperative biomarker trajectories after general and spinal anesthesia remain limited. This prospective observational study aimed to compare circulating neuron-specific enolase (NSE), adiponectin, and visinin-like protein-1 (VSNL1) in adults undergoing elective surgery under general anesthesia (GA) or spinal anesthesia (SA). Ninety-seven patients (GA, n = 52; SA, n = 45) underwent serum sampling preoperatively and at 6 and 24 hours postoperatively, and biomarker concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Longitudinal associations were assessed using linear mixed-effects models adjusted for age, body mass index (BMI), operation duration, and surgical procedure type, with additional baseline-adjusted analyses for adiponectin. NSE increased in both groups but rose less in the SA group than in the GA group at 6 hours (adjusted interaction estimate, -7.765 ng/mL; p < 0.001) and 24 hours (-4.005 ng/mL; p < 0.001). Adiponectin decreased postoperatively, but group-by-time interactions were not significant, and baseline-adjusted analyses showed no significant association between anesthesia modality and adiponectin at either postoperative time point. VSNL1 increased over time; the group-by-time interaction was not significant at 6 hours but was significant at 24 hours (estimate, 0.635 ng/mL; p < 0.001), indicating a differential late trajectory. Perioperative biomarker trajectories differed between GA and SA, most consistently for NSE. However, nonrandom anesthesia assignment, substantial differences in surgical case mix and operation duration, and the absence of neurocognitive outcome assessment preclude causal or clinical interpretation. These findings should be regarded as exploratory adjusted associations and validated in larger, more homogeneous surgical cohorts.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hantavirus infections in Southeastern Europe - Epidemiology, outbreak dynamics, and One Health preparedness: A narrative review.","authors":"Edmond Puca, Rok Čivljak, Aleksandra Barac, Luka Laura, Goran Stevanovic, Magdalena Baymakova, Sotirios Tsiodras, Casandra Bulescu, Gramoz Bunjaku, Jurica Arapović","doi":"10.17305/bb.2026.14790","DOIUrl":"https://doi.org/10.17305/bb.2026.14790","url":null,"abstract":"<p><p>Human-pathogenic orthohantaviruses are significant rodent-borne zoonotic pathogens in Europe. Southeastern Europe (SEE) is a distinct endemic region where Dobrava-Belgrade virus (DOBV) and Puumala virus (PUUV) co-circulate, causing hemorrhagic fever with renal syndrome (HFRS) of varying severity. This narrative review synthesizes the epidemiology, transmission dynamics, clinical characteristics, ecological drivers, and public health challenges of hantavirus infections across SEE, identifying priorities for regional preparedness. We searched PubMed, Scopus, and Web of Science from their inception through June 2026, supplementing with reference screening. Regional epidemiological patterns were assessed descriptively using national surveillance data, European surveillance reports, published studies, and available population-based incidence estimates. Long-term surveillance reveals persistent endemic transmission with significant geographic and interannual heterogeneity. Slovenia and Croatia exhibit the highest cumulative burden and most pronounced periods of increased HFRS activity. Several years-2008, 2012, 2014, 2017, 2019, 2021, and 2023-showed partially synchronized increases across multiple neighboring countries. These patterns align with shared ecological influences, including rodent population fluctuations, mast-seeding events, and climatic variability. However, local ecology, human exposure, and differences in surveillance capacity modify their magnitude. The coexistence of generally milder PUUV-associated disease and more severe DOBV-associated HFRS further distinguishes SEE's clinical landscape. Therefore, hantavirus epidemiology in SEE is best understood as an interconnected regional ecological system. Integrated human, animal, environmental, and genomic surveillance within a coordinated One Health framework is crucial for improving outbreak prediction, cross-border preparedness, and future disease control.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota-associated metabolites and microbial components in acute ischemic stroke - Neuroimmune inflammation, biomarkers, and therapeutic targets: A narrative review.","authors":"Zhiyuan Hou, Yingyue Ding, Xu Wang, Meilin Pan, Jinjian Li, Dexi Zhao","doi":"10.17305/bb.2026.14621","DOIUrl":"https://doi.org/10.17305/bb.2026.14621","url":null,"abstract":"<p><p>Acute ischemic stroke (AIS) induces gut microbiota dysbiosis and intestinal barrier disruption, potentially influencing neuroimmune inflammation via altered microbial metabolites and components. This narrative review synthesizes current evidence on the mechanisms, biomarker potential, and therapeutic implications of gut microbiota-associated molecules in AIS. We searched PubMed, Web of Science, and Scopus for peer-reviewed studies published between May 1999 and May 2026. From 283 identified records, 87 animal and clinical studies met eligibility and were included. Evidence indicates that trimethylamine N-oxide (TMAO), lipopolysaccharide (LPS), and the tryptophan (TRP)-derived metabolite quinolinic acid predominantly promote neuroinflammation. They achieve this by disrupting blood-brain barrier integrity, activating pro-inflammatory signaling, inducing excitotoxicity, or enhancing thrombosis. Conversely, short-chain fatty acids (SCFAs), kynurenic acid, indole-3-propionic acid, and secondary bile acids exert anti-inflammatory and neuroprotective effects through immune modulation and microglial polarization. Clinical studies suggest TMAO may aid first-stroke risk stratification, while fecal SCFAs, TRP-related metabolites, and circulating bile acids show potential for assessing stroke severity or functional prognosis. However, findings vary based on specimen type, disease stage, and sampling time. Therapeutic approaches targeting these molecules-including metabolite supplementation, modulation of endogenous metabolite production, and nanodelivery systems-have shown encouraging effects, primarily in preclinical models. In conclusion, gut microbiota-associated metabolites and microbial components represent promising AIS biomarkers and therapeutic targets. However, substantial methodological heterogeneity and limited clinical validation currently restrict their translation into routine practice for ischemic stroke management.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ESAT-6-specific antibody features and Fcγ receptor expression during pulmonary tuberculosis treatment: Implications for therapeutic monitoring.","authors":"Christian Elugo, Sandra Palma Albornoz, Yomara Romero, Sandra Delgado-Málaga, Iskra Tuero","doi":"10.17305/bb.2026.14489","DOIUrl":"https://doi.org/10.17305/bb.2026.14489","url":null,"abstract":"<p><p>Tuberculosis (TB) remains a leading cause of global mortality, yet the long-term dynamics of antibody-mediated immunity during successful treatment are not fully understood. This study aimed to characterize how ESAT-6-specific antibody profiles, Fc gamma receptor (FcγR) expression, and antibody effector functions change in pulmonary TB patients undergoing treatment. In this exploratory longitudinal study, 21 adults with active pulmonary TB, who completed standard six-month therapy and achieved microbiological cure, were sampled at three time points: before treatment, after two months, and at treatment completion. We quantified ESAT-6-specific immunoglobulin G (IgG) and its subclasses using enzyme-linked immunosorbent assay (ELISA). FcγR expression was assessed via flow cytometry, and antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) were evaluated with cell-based assays. Upon treatment completion, ESAT-6-specific total IgG and IgG4 significantly decreased from baseline in 85.7% and 81.0% of participants, respectively (both q < 0.001). Conversely, ADCP and ADCC increased in 76.2% of participants (q = 0.0017 and q = 0.0014, respectively). Activating FcγR expression also declined, most consistently for CD64 on granulocytes and monocytes, with additional reductions in CD16 and CD32 on monocytes. These findings reveal a coordinated remodeling of ESAT-6-specific humoral immunity during successful TB treatment. We identify IgG4 levels, FcγR expression, ADCP, and ADCC as potential correlates of treatment response. Further validation in larger prospective cohorts, including patients experiencing treatment failure and relapse, is necessary.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced E-cadherin, claudin-1, and claudin-6 expression and compartment-specific lymphocyte distribution in recurrent aphthous ulceration.","authors":"Efe Yetişgin, Çiğdem Sercan, Ertuğrul Çelik, Eda Yılmaz Akçay, Ömer Günhan","doi":"10.17305/bb.2026.14856","DOIUrl":"https://doi.org/10.17305/bb.2026.14856","url":null,"abstract":"<p><p>Recurrent aphthous ulceration (RAU) is a prevalent inflammatory condition affecting the oral mucosa. However, the localized epithelial junctional changes and their connection to immune cell distribution are not well understood. This study sought to characterize junction-associated protein expression and compartment-specific lymphocyte distribution in RAU. This retrospective, multicenter, paired tissue study included 56 consecutive patients with clinically and histopathologically confirmed RAU. Semiquantitative immunohistochemistry was employed to compare E-cadherin, claudin-1, and claudin-6 expression. Comparisons were made between ulcer-adjacent non-ulcerated regenerative epithelium and morphologically preserved distant mucosa from the same patient. The study also evaluated cluster of differentiation 4 (CD4)-, cluster of differentiation 8 (CD8)-, and cluster of differentiation 20 (CD20)-positive lymphocytes in both intraepithelial and subepithelial/ulcer-base compartments. All distant mucosal samples exhibited strong expression of the three junctional proteins. In contrast, within the ulcer-adjacent epithelium, E-cadherin expression was weak in 35.7% and moderate in 64.3% of cases. Claudin-1 was absent in 17.9% and weak in 82.1%, while claudin-6 was absent in 71.4% and weak in 28.6%. Each marker demonstrated significantly lower expression in all paired cases (p < 0.001). Descriptively, CD8-positive lymphocytes were consistently present intraepithelially in all cases, whereas CD20-positive lymphocytes were absent. The ulcer base and adjacent subepithelial tissue contained CD4-, CD8-, and CD20-positive lymphocytes in all cases. RAU is consistently linked to a localized reduction of epithelial junctional proteins and distinct compartmental lymphocyte patterns. These findings suggest epithelial junctional remodeling within the RAU microenvironment, though they do not confirm functional barrier impairment or causality.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood urea nitrogen-to-albumin ratio and in-hospital mortality in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.","authors":"Şükriye Uslu, Ahmet Genç, Gülsüm Meral Yılmaz Öztekin, Görkem Kuş, Şakir Arslan","doi":"10.17305/bb.2026.14730","DOIUrl":"https://doi.org/10.17305/bb.2026.14730","url":null,"abstract":"<p><p>In-hospital mortality remains an important concern in patients with ST-elevation myocardial infarction (STEMI), highlighting the need for simple and readily available markers for early risk stratification. This study investigated the prognostic value of the blood urea nitrogen-to-serum albumin ratio (BAR) for in-hospital mortality in patients with STEMI undergoing primary percutaneous coronary intervention (pPCI). This single-center retrospective cohort study included 388 consecutive patients who underwent pPCI in 2024. Admission BAR was calculated using blood urea nitrogen (mg/dL) and serum albumin (g/L). Its association with in-hospital mortality was evaluated using receiver operating characteristic analysis and exploratory multivariable logistic regression, with Firth-penalized regression and bootstrap validation performed as sensitivity analyses. In-hospital death occurred in 18 patients (4.6%). Patients who died had significantly higher BAR values than survivors (0.7 vs. 0.4, p < 0.001). BAR showed good discrimination for in-hospital mortality, with an area under the curve of 0.869 (p < 0.001); the bootstrap-corrected area under the curve was also 0.869. An exploratory cut-off of 0.475 yielded 83.3% sensitivity and 75.4% specificity. In the multivariable model, each 0.1-unit increase in BAR was associated with higher odds of in-hospital mortality (odds ratio 1.412, 95% confidence interval 1.161-1.718; p = 0.0006), with a similar estimate in the Firth-penalized analysis (odds ratio 1.346, 95% confidence interval 1.121-1.616; p = 0.0008). Admission BAR may represent a simple candidate marker for early mortality risk stratification in STEMI patients undergoing pPCI; however, its prognostic performance and clinical utility require validation in larger prospective multicenter cohorts.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-translational modifications in sepsis-induced myocardial dysfunction - Molecular mechanisms and therapeutic targets: A review.","authors":"Xuan Liu, Haihua Pan, Jun Cha, Ruochen Sun, Chaojie He","doi":"10.17305/bb.2026.14517","DOIUrl":"https://doi.org/10.17305/bb.2026.14517","url":null,"abstract":"<p><p>Sepsis-induced myocardial dysfunction (SIMD) is a frequent and life-threatening complication of sepsis driven by interconnected inflammatory, oxidative, metabolic, and mitochondrial disturbances. Post-translational modifications (PTMs) have emerged as key regulators of these processes by dynamically altering protein activity, stability, localization, and signaling. This narrative review aimed to summarize the roles of major PTMs in SIMD and evaluate their potential as therapeutic targets. Relevant original studies and authoritative reviews published predominantly within the past decade were identified through targeted searches of PubMed and Web of Science and qualitatively synthesized. Current evidence indicates that phosphorylation, acetylation, ubiquitination, protein methylation, ADP-ribosylation, and palmitoylation regulate major pathways involved in myocardial inflammation, oxidative stress, mitochondrial dysfunction, metabolic reprogramming, apoptosis, and impaired contractility. Crosstalk among these modifications further integrates signaling networks, while upstream epigenetic mechanisms, including DNA methylation and N6-methyladenosine RNA modification, can influence PTM-related enzymes and downstream signaling. Experimental studies also suggest that pharmacological modulation of PTM-regulated pathways may attenuate myocardial injury; however, most mechanistic and therapeutic evidence derives from animal models and cultured cells, with limited validation in human septic myocardium. PTMs therefore represent promising mechanistic and therapeutic targets in SIMD, but systematic characterization of PTM crosstalk and rigorous human translational studies are required before PTM-directed strategies can be incorporated into clinical practice.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel peptide inhibitors targeting the TGF-β receptor I/II complex modulate SMAD and ERK signaling <i>in vitro</i>.","authors":"Jacek Plichta, Michał Seweryn Karbownik, Piotr Kuna, Michał Panek","doi":"10.17305/bb.2026.14724","DOIUrl":"https://doi.org/10.17305/bb.2026.14724","url":null,"abstract":"<p><p>Transforming growth factor-β (TGF-β) contributes to fibrosis, immunosuppression, and tumor progression, but systemic TGF-β inhibition is limited by toxicity and lack of selectivity. This exploratory proof-of-concept study evaluated novel peptides designed to target the TGF-β receptor I/II complex and examined their effects on canonical and noncanonical TGF-β signaling in vitro. Peptides 2_5 and 2_6, selected by in silico docking of receptor-ligand interface-derived sequences, were tested in human embryonic kidney 293T (HEK293T) cells at 20 and 50 μM, with the TGF-β receptor I inhibitor SD-208 as a reference. Total and phosphorylated SMAD2, SMAD3, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) were assessed by Western blotting and densitometry. Peptide 2_5 showed the strongest activity, reducing total ERK1/2 by 65% at 50 μM and phosphorylated ERK1/2 by 90.4% and 83.4% at 20 and 50 μM, respectively; SD-208 reduced total and phosphorylated ERK1/2 by 64.3% and 54.5%, respectively. Peptide 2_5 also reduced total SMAD2 by 81% at 50 μM, whereas its effect on SMAD2 phosphorylation was inconsistent. Peptide 2_6 showed minimal effects, JNK was largely unaffected, and SMAD3 results were inconclusive because of weak signals. These preliminary findings suggest that peptide 2_5 may differentially modulate TGF-β signaling, with a stronger effect on ERK1/2 than on SMAD2; however, receptor targeting and pathway selectivity require confirmation in fully replicated quantitative studies.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulatory and other-cause mortality after neoadjuvant versus adjuvant chemotherapy in women with stage II-III breast cancer.","authors":"Burcu Zihni, İsmail Zihni, Mehmet Zafer Sabuncuoğlu","doi":"10.17305/bb.2026.14742","DOIUrl":"https://doi.org/10.17305/bb.2026.14742","url":null,"abstract":"<p><p>Most women with operable breast cancer increasingly survive long enough for non-cancer causes to become important contributors to mortality, particularly at older ages. We investigated whether the recorded sequence of systemic therapy relative to surgery among women receiving chemotherapy was associated with circulatory mortality and examined how causes of death evolve in long-term survivors. This retrospective population-based cohort study included 74,233 women with stage II-III non-metastatic invasive breast cancer diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database who received chemotherapy and definitive surgery. A six-month landmark was used to reduce immortal-time bias, and treatment groups were balanced using stabilized inverse-probability-of-treatment weighting. Weighted cumulative incidence, cause-specific hazard, and Fine-Gray subdistribution models were used to evaluate circulatory mortality, while mortality patterns after a five-year landmark were examined descriptively by age. Median follow-up was 10.8 years. The weighted 10-year cumulative incidence of circulatory death was 2.06% after recorded preoperative systemic therapy and 2.10% after postoperative therapy, corresponding to a risk difference of -0.05 percentage points (95% confidence interval [CI], -0.31 to 0.18). The cause-specific hazard ratio was 1.092 (95% CI, 0.968-1.231), and the subdistribution hazard ratio was 1.024 (95% CI, 0.920-1.140). Among deaths occurring after the five-year landmark, the circulatory share increased with age, reaching 25.5% in women aged ≥75 years at diagnosis; however, other non-circulatory causes remained the largest category (49.9%). In women aged ≥75 years who survived five years, circulatory mortality approached and eventually exceeded breast-cancer mortality, but the difference was not significant at the prespecified seven-year time point. The recorded systemic-therapy/surgery sequence was not associated with long-term circulatory mortality. In older long-term breast-cancer survivors, late mortality is predominantly multimorbid rather than circulatory-dominant, supporting survivorship care that addresses cardiovascular risk within a broader framework of age-related competing health risks.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}