Background A comprehensive evaluation between PD-1 and PD-L1 inhibitors is critical for appropriate treatment choice. To evaluate the efficacy and safety of PD-1 and PD-L1 inhibitors, this meta-analysis was conducted through adjusted indirect comparison. Methods Systematic literature search was conducted in PubMed, Embase, and Cochrane Central databases from January 1st 2000 to January 31st 2023. Randomized controlled trials (RCT) comparing PD-1/PD-L1 inhibitors with standard treatments in solid tumors were retrieved. Eligible RCTs regarding PD-1/PD-L1 inhibitors were matched as mirror groups according to the same population and study design. Hazard ratio (HR) for overall survival (OS), progression-free survival (PFS), and disease-free/event-free survival (DFS/EFS), and risk ratio (RR) for objective response rate (ORR) and adverse events (AEs) were generated from indirect comparisons in each mirror group and pooled for overall meta-analysis. Results In total, 96 eligible RCTs with 104 arms of 56,597 patients were identified to construct 32 mirror groups. Patients treated with PD-1 inhibitors exhibited improved OS (HR, 0.86 [95% CI: 0.81, 0.90]; P < 0.001), PFS (HR, 0.85 [95% CI: 0.75, 0.96]; P = 0.01), and DFS/EFS (HR, 0.81 (95% CI: 0.70, 0.94]; P = 0.005) in all populations compared with those with PD-L1 inhibitors, together with a higher ORR (RR, 1.12 [95% CI: 1.04, 1.20]; P = 0.002). While PD-1 inhibitors showed comparable rates of treatment-related AEs with PD-L1 inhibitors, PD-1 inhibitors demonstrated a higher discontinuation rate due to treatment-related AEs (RR, 2.27 [95% CI: 1.91, 2.70]; P < 0.0001). Conclusions This meta-analysis revealed that PD-1 inhibitors exhibited better survival outcomes compared with PD-L1 inhibitors in solid tumors with comparable safety profiles except for a higher discontinuation rate. This systematic review was registered in PROSPERO as CRD42023452639.

BACKGROUND:With steadily rising survival rates, the cause-of-death landscape for breast cancer patients is evolving. This study. AIMS:to delineate mortality patterns and demographic disparities to inform long-term survivorship strategies. METHODS:We performed a retrospective analysis of 839,698 breast cancer patients from U.S. population-based registries (2000-2021). Standardized Mortality Ratios (SMRs) and Incidence Rate Ratios (IRRs) were calculated to assess the risk of non-cancer deaths across age and racial/ethnic groups. RESULTS:By 10 years of follow-up, 48.6% of all deaths were attributed to non-cancer causes. Significant disparities emerged: Black patients (aged 0-54) exhibited the highest all-cause mortality risk (IRR: 1.70; 95% CI: 1.66-1.74), whereas Asian/Pacific Islanders (aged 65-74) showed the lowest (IRR: 0.67; 95% CI: 0.65-0.69). Notably, patients faced drastically elevated risks for external causes, including suicide (SMR: 17.4; 95% CI: 16.1-18.8) and homicide (SMR: 10.1; 95% CI: 8.37-12.13), alongside cardiovascular/non-cancer diseases. CONCLUSION:Mortality in breast cancer survivors is progressively shifting from malignancy to non-cancer causes, with distinct racial and age-dependent patterns. These findings necessitate a paradigm shift toward personalized, risk-stratified survivorship care that integrates cardiovascular monitoring and psychosocial interventions.

Tumor necrosis factor-α-stimulated gene-6(TSG-6), a secreted protein with anti-inflammatory and tissue-protective properties, mediates a cascade of proinflammatory cytokines and ameliorates tissue fibrosis. Previous studies have found that TSG-6 can attenuate the degree of fibrosis, inhibit the inflammatory response, and reduce adipogenesis in orbital tissues in a Thyroid Eye Disease (TED) mouse model of thyroid-eye disease; however, the exact mechanism has not been elucidated. In the present study, we investigated the mechanism by which TSG-6 exerts its anti-inflammatory and antifibrotic effects in an in vitro cellular model of TED. Human orbital connective tissue was collected from primary and passaged cultures and 3-5 passages-cells were used in subsequent experiments. The expression of relevant inflammatory markers, including tumor necrosis factor-α(TNF-α), Interleukin-6(IL-6), monocyte chemoattractant protein-1(MCP-1), Cyclooxygenase-2(COX-2), and intercellular cell adhesion molecule-1(ICAM-1), was detected by western blotting with 5, 10, and 15 ng/ml TSG-6 pretreatment in the presence or absence of 10 ng/ml Interleukin-1beta (IL-1β) and H2DCFDA (DCFH-DA) fluorescent staining, and flow cytometry was used to detect reactive oxygen species(ROS) indices. Orbital fibroblasts (OF) were treated with TSG-6 in the presence or absence of transforming growth factor-beta 1(TGF-β1) agonist (SRI-011381:MCE, HY-100347) and the expression of TGF-β1/Smad pathway-associated fibrosis factors, including α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), and collagen type 1 (COL1A1). TSG-6 inhibited IL-1β-induced production of the inflammatory mediators TNF-α, IL-6, MCP-1, COX-2, and ICAM-1, and the release of ROS in a dose-dependent manner in an in vitro cell model of TED. TSG-6 downregulated the expression of TGF-β1, Smad2/3, p-smad2/3, α-SMA, CTGF, and COL1A1 in a dose-dependent manner after TGF-β1 pretreatment and reduced the phosphorylation of Smad2/3, suggesting that TSG-6 inhibits the TGF-β1 signaling cascade response in orbital fibroblasts. TSG-6 inhibited the production of inflammatory mediators and the release of ROS, and suppressed fibrosis of human orbital fibroblasts by downregulating the TGF-β1/Smad pathway. These data suggest a potential application of TSG-6 in the treatment of TED and provide a novel target for the treatment of TED.

BACKGROUND:The role of angiogenesis inhibitors in breast cancer (BC) remains unclear. Potential synergistic activity is observed between antiangiogenic tyrosine kinase inhibitors and cyclin-dependent kinase 4/6 inhibitors. This trial evaluated the feasibility of combining the angiogenesis-targeting tyrosine kinase inhibitor famitinib with the cyclin-dependent kinase 4/6 inhibitor dalpiciclib in patients with hormone receptor-positive human epidermal growth factor receptor 2-negative (HR+/HER2-) BC. METHODS:Patients with HR+/HER2- advanced BC were enrolled and treated with famitinib and dalpiciclib in combination with fulvestrant. A phase Ib dose-escalation study using a standard 3+3 design was conducted to determine the recommended phase II dose (RP2D). Phase II subsequently assessed the efficacy and safety of the RP2D. Exploratory biomarker analyses were performed to evaluate key gene mutations associated with this BC subtype, including PIK3CA and BRCA1/2. RESULTS:Based on dose-limiting toxicities and preliminary efficacy, daily famitinib 10 mg combined with dalpiciclib 100 mg plus fulvestrant was selected as the RP2D. An additional 28 patients were enrolled in phase II. The confirmed objective response rate (ORR) was 51.9% (95% confidence interval [CI]: 32.0%-71.3%), with a median progression-free survival (PFS) of 15.7 (95% CI: 7.3-25.4) months. The 2-year overall survival rate was 96.3% (95% CI: 76.5%-99.5%). Comparable ORRs and median PFS were observed regardless of PIK3CA or BRCA1/2 mutation status. Treatment-related adverse events of grade ≥3 were predominantly hematologic, including decreased neutrophil count (96.4%), decreased leukocyte count (75.0%), and decreased platelet count (10.7%). Patient enrollment was terminated after a comprehensive assessment of the benefit-risk profile of this regimen. CONCLUSIONS:Although the objective response threshold in the first stage of phase II was met, the median PFS did not demonstrate superiority over standard front-line regimens for HR+/HER2- advanced BC, and overlapping hematologic toxicities were observed. TRIAL REGISTRATION:ClinicalTrials.gov (NCT05176080) and Chictr.org.cn (ChiCTR2100053950).

Breast cancer is the most common malignancy among women worldwide and exhibits marked heterogeneity. Among its various subtypes, triple-negative breast cancer (TNBC) is associated with an inferior prognosis. Although molecular stratification tools such as Oncotype DX and MammaPrint have been adopted in clinical settings, prognostic models based on chromosomal instability remain inadequate. The centromere protein (CENP) family, as a key regulator of genomic stability, has been closely linked to tumor progression due to its aberrant expression. In this study, we integrated multi-omics data—including RNA transcriptomic profiles and single-cell RNA sequencing—and employed weighted gene co-expression network analysis (WGCNA) to identify core gene modules associated with CENPA. A prognostic risk model was developed using Cox regression analysis and the LASSO algorithm. Validation in independent cohorts demonstrated that the model effectively stratified patients into high- and low-risk groups, with the high-risk group showing significantly reduced five-year survival (p < 0.001). Furthermore, the single-cell analysis revealed that CENPA-high subpopulations were enriched in proliferative tumor cells and were associated with an immunosuppressive tumor microenvironment. This study is the first to systematically construct a CENP-based prognostic model for breast cancer, providing novel molecular biomarkers and potential therapeutic targets for personalized treatment. The biological function of the key molecule MMP1 in breast cancer was further validated through both in vitro and in vivo experiments.

The clinical efficacy of immunotherapy in advanced esophageal squamous cell carcinoma (ESCC) remains suboptimal, as most patients eventually develop drug resistance and experience disease progression. Here, we identify Collagen Triple Helix Repeat Containing 1 (CTHRC1) as a critical mediator of immunotherapy resistance in ESCC. Elevated CTHRC1 expression was observed in tumors unresponsive to immune checkpoint blockade and was associated with enhanced platelet activity and infiltration of megakaryocytes (MKs) into the tumor microenvironment. Mechanistically, CTHRC1 facilitated MK activation and recruitment, fostering an immunosuppressive niche that impaired cytotoxic T-cell activity and promoted cell exhaustion. To therapeutically target this axis, we developed a lipid nanoparticle (LNP)-encapsulated mRNA vaccine encoding CTHRC1. In preclinical ESCC models, the CTHRC1-mRNA-LNP vaccine elicited robust antitumor immunity. Notably, the combination of CTHRC1-mRNA vaccination with anti–PD-1 therapy induced synergistic intratumoral T-cell infiltration, depletion of MKs, reversal of immunosuppression, and durable tumor regression. Collectively, these findings uncover an unrecognized immunoregulatory function of CTHRC1 in ESCC and highlight its therapeutic targeting as a promising strategy to enhance the efficacy of immune checkpoint blockade. CTHRC1 directly engages integrin αIIbβ3 and to drive megakaryocyte and activates the TLR4–NF-κB-IL-8 axis to promote megakaryocyte/platelet infiltration, promoting an immunosuppressive ESCC TME and T-cell dysfunction. Administration of a CTHRC1 mRNA–LNP vaccine elicits potent antigen-specific humoral and cellular immunity, dismantles megakaryocyte-mediated immune exclusion, converts a cold TME into an inflamed state, and restores sensitivity to PD-1 blockade.

Breast cancer remains a leading cause of morbidity and mortality among women worldwide, with significant heterogeneity in its development and treatment response. Recent advances in understanding the roles of the microbiome and epigenetic regulation have opened new avenues for addressing the complexities of breast cancer progression and therapeutic resistance. This review explores the intricate relationship between the gut and intratumoral microbiomes and epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNAs. Specifically, we examine how microbial metabolites, particularly short-chain fatty acids (SCFAs), regulate gene expression via epigenetic mechanisms, influencing tumor growth, metastasis, and treatment response. The impact of metabolic diseases, including obesity and type 2 diabetes mellitus (T2DM), on breast cancer risk through microbiome-mediated epigenetic changes is also discussed. Furthermore, the review highlights emerging therapeutic strategies that integrate microbiome modulation with epigenetic therapies, including the use of probiotics, dietary interventions, and fecal microbiota transplantation (FMT), as well as DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors. These innovative approaches hold promise for overcoming treatment resistance and improving clinical outcomes in breast cancer patients. Future research should focus on elucidating the molecular pathways through which the microbiome influences epigenetic regulation and developing personalized, microbiome-targeted therapies that enhance the efficacy of existing treatments. By targeting both the genetic and epigenetic drivers of breast cancer, microbiome-based interventions represent a novel frontier in the fight against this challenging disease.

Introduction Survival outcomes for early-stage breast cancer have improved substantially; however, many survivors experience persistent treatment-related toxicities that adversely affect long-term quality of life (QoL) and functional recovery. Prospective survivorship data from China remain limited. The PERSEVERE study aims to characterise longitudinal trajectories of QoL and treatment-related toxicities among Chinese women treated for stage I–III breast cancer and to identify factors associated with suboptimal recovery.Methods and analysis PERSEVERE is a prospective, multicentre, observational cohort study enrolling approximately 3000 women with newly diagnosed stage I–III invasive breast cancer across cancer centres in China. Data are collected at baseline and serially for up to 5 years, including clinical variables, a validated suite of patient-reported outcome measures collected via a centralised REDCap electronic platform and baseline biospecimens. The primary outcome is the change in the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 global health status/QoL score from baseline to 12 months. Longitudinal and time-to-event analytical approaches appropriate for observational cohort studies will be applied, with exploratory analyses planned to investigate symptom trajectories and biological correlates.Ethics and dissemination The study protocol (ID: NCC25/629-5575) has been approved by the Independent Ethics Committee of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences. Written informed consent will be obtained from all participants. Study findings will be disseminated through peer-reviewed open-access publications and presentations at national and international conferences, with summaries shared with clinicians and patient advocacy groups.Trial registration number NCT07010939.

Although cancer immunotherapy has revolutionized oncology, its clinical efficacy remains substantially limited by both primary and acquired resistance. These resistance mechanisms are largely driven by complex biological barriers within the tumor microenvironment (TME) and insufficient tumor immunogenicity. Nanotechnology offers a promising strategy to overcome these barriers by enabling precise spatiotemporal control of immune activation. This review provides a comprehensive analysis of emerging nanoparticle-based strategies designed to overcome immunotherapy resistance. Moving beyond conventional drug delivery, we highlight the paradigm shift from empirical engineering to artificial intelligence (AI)-driven design and precision medicine. We critically examine advanced mechanisms for remodeling the hypoxic TME, normalizing tumor vasculature, and reversing immunosuppression by activating the Stimulator of Interferon Genes (STING) pathway and inducing immunogenic cell death (ICD). Furthermore, we discuss integrating AI and machine learning to predict tumor-specific neoantigens and optimize nanocarrier properties, enabling the development of personalized mRNA nanovaccines. Finally, we address key translational challenges—including safety considerations, scalable manufacturing, and regulatory frameworks—that must be addressed to bridge the gap between laboratory innovation and clinical application. Collectively, these advances provide a roadmap for the next generation of smart, mechanism-driven nano-immunotherapeutics capable of transforming immunologically "cold" tumors into "hot" ones.

BACKGROUND:Suspicious calcifications in breast cancer (BC) often limit eligibility for breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC). This study assessed the impact of ductal carcinoma in situ (DCIS) status and post-NAC imaging changes on pathological complete response (pCR), BCS feasibility, and prognosis. METHODS:We retrospectively analyzed 163 BC patients with suspicious calcifications treated with NAC (median follow-up, 38.9 months). Logistic regression identified predictors of pCR, associations between calcification changes and pCR were assessed using Cramer's V, and OS and DFS were evaluated using Kaplan-Meier analysis. RESULTS:73 patients had DCIS and 90 had non-DCIS. Calcification reduction after NAC was more frequent in non-DCIS group (56.7%; p = 0.012). pCR rates were higher in non-DCIS group than in DCIS group (73.7% vs 26.3%; p = 0.015). After adjustment, DCIS was associated with reduced pCR rates (OR: 0.26, 95% CI: 0.08-0.73). Overall BCS rate was 11%. Calcification reduction showed a weak correlation with pCR (Cramer's V = 0.321). No significant OS, DFS, or BCS differences were observed by DCIS status or calcification change within follow-up. CONCLUSION:DCIS is associated with reduced pCR after NAC. Calcification findings alone should be interpreted cautiously, and BCS feasibility should be assessed using comprehensive surgical criteria.

ObjectiveTo compare long-term survival in early-stage breast cancer patients treated with different radiation therapy modalities.MethodsData was retrospectively derived from SEER database. We compared overall survival (OS), breast cancer specific survival (BCSS) and second primary malignancies (SPM) in early-stage breast cancer patients treated with postoperative radiotherapy (PORT) versus those treated neoadjuvant radiotherapy (NART) and intraoperative radiotherapy (IORT) after propensity score matching by 1:1.ResultsA total of 457,166 patients were included in this study. After matching, the 20-year OS of 1441 patients in NART cohort was lower than that in PORT cohort (p < 0.01), particularly in hormone receptor positive patients (p < 0.01). NART were dependent prognostic factors for 20-year OS [Hazard Ratio (HR):1.21, 95%CI: 1.06-1.38, p < 0.01). No significant difference in BCSS was observed between NART and PORT treatments. Additionally, patients undergoing NART had a lower risk of all SPM (p = 0.01) and second solid cancers (p = 0.02) but a comparable risk of second hematological malignancies (p = 0.55) than patients administered PORT. HR-positive was a risk factor for SPM. No OS, BCSS or SPM risk difference were significantly observed in the 2096 pairs of IORT and PORT groups.ConclusionCompared to PORT, NART and IORT don't offer survival advantages for early-stage breast cancer patients. Altering the sequence of radiotherapy requires careful evaluation.

BACKGROUND:Breast cancer-related lymphedema (BCRL) is relatively common in postoperative breast cancer patients, requiring early, lifelong prevention. However, these patients often have low preventive behavioral intention, with unclear influencing factors, and their internal links urgently need a systematic analysis of these interrelationships. METHODS:A cross-sectional survey was conducted on 672 breast cancer survivors at different postoperative stages to collect sociodemographic data and psychological variables related to lymphedema preventive intention. After univariate analysis of sociodemographic data, binary logistic regression identified significant predictors of intention, and path analysis elucidated the directional relationships between psychological variables and preventive intention. RESULTS:Multidimensional interventions that strengthen lymphedema prevention knowledge and enhance self-efficacy, risk perception, and positive expectations are likely to increase the preventive behavioral intentions of breast cancer survivors and promote active self-management after hospital discharge. CONCLUSIONS:Multidimensional interventions that reinforce lymphedema prevention knowledge and enhance self-efficacy, risk perception, and positive expectation are likely to increase the preventive behavioral intention of breast cancer survivors and encourage active self-management after hospital discharge.

1123 Background: TROP2 and HER3 are frequently overexpressed in most of solid tumors. JSKN016 is a first-in-class bispecific ADC targeting TROP2/HER3, site specifically conjugated to topoisomerase I inhibitor via a cleavable linker (DAR4). Glycan conjugation provides high stability and minimizes off-target toxicity. Methods: JSKN016-101 (NCT06592417) is a first-in-human, dose-escalation and expansion study in China, enrolling patients with advanced solid tumors to receive JSKN016 monotherapy. This analysis focused on the HER2-negative BC cohort. Results: As of December 22, 2025, JSKN016 was escalated to 8 mg/kg IV Q3W without reaching the maximum tolerated dose. A total of 82 HER2- BC pts were enrolled: 50 TNBC and 32 HR+/HER2- BC, treated at 4 mg/kg (n=14), 6 mg/kg (recommended phase II dose [RP2D]; n=65), and 8 mg/kg (n=3). Overall, 98.8% (81/82) had stage IV disease including 13.4% (11/82) with brain metastases. Median age was 50 (TNBC) and 52y (HR+/HER2- BC); ECOG PS 1 was reported in 78.7% and 76.7%, respectively. All TNBC pts had prior taxane-based chemotherapy, 28.0% had received ≥3 prior systemic regimens. All HR+/HER2- BC pts had progressed after ≥1 endocrine therapy with CDK4/6 inhibition and ≥1 chemotherapy. Among 47 efficacy-evaluable TNBC pts, objective response rate (ORR) was 61.7% (by INV and IRC). At RP2D (n=31), ORR was 64.5% (INV) and 61.3% (IRC), with disease control rates (DCR) of 83.9% and 90.3%. The median PFS was 7.9 months (95%CI: 5.5, NE) by IRC and 7.6 months (95%CI: 4.1, NE) by INV. Among 30 efficacy-evaluable HR+/HER2- BC pts, ORR was 50.0% (INV) and 53.3% (IRC); at RP2D (n=29), ORR was 51.7% (INV) and 55.2% (IRC), with DCR of both 100%. The median PFS was 11.1 months (8.3, NE) by IRC and was not yet mature by INV. With a median follow-up of 8 months, grade 3 or above TRAEs occurred in 25.6% (21/82) pts, with no G4 or 5 events reported. The most common G3 TRAEs were neutrophil count decreased (6.1%), amylase increased (4.9%), white blood cell count decreased (4.9%), stomatitis (3.7%), asthenia (2.4%), lymphopenia (2.4%). The incidence of TRAEs was 9.8%. Only one TRAE (G3 conjunctivitis) led to treatment discontinuation. No interstitial lung disease (ILD) was reported. Conclusions: JSKN016 demonstrated robust antitumor activity with good safety profile in pts with HER2-negative BC. The results support further development of JSKN016 as monotherapy or in combination. Clinical trial information: NCT06592417 . Efficacy of JSKN016 in HER2-BC at 6 mg/kg Q3W. TNBC (N=31) HR+/HER2- BC (N=29) Assessed by INV IRC INV IRC uORR, % (95% CI) 64.5 (45.4, 80.8) 61.3 (42.2, 78.2) 51.7 (32.5, 70.6) 55.2 (35.7, 73.6) DCR, % (95% CI) 83.9 (66.3, 94.5) 90.3 (74.2, 98.0) 100 (88.1, 100) 100 (88.1, 100) mPFS, mos (95% CI) 7.6 (4.1, NE) 7.9 (5.5, NE) NR 11.1 (8.3, NE) 6-months PFS rate, % 57.7 (38.5, 72.9) 68.4 (47.9, 82.2) 74.0 (53.0, 86.7) 84.5 (63.8, 93.9)

The present study aimed to evaluate the incidence of short-term complications and health-related quality of life (HRQoL) in patients with breast cancer undergoing breast-conserving surgery (BCS) with intraoperative radiotherapy (IORT), and to identify associated influencing factors. The study prospectively analyzed clinical data from women who underwent BCS with IORT at Tianjin Medical University Cancer Institute and Hospital (Tianjin, China) between March 2021 and June 2023. Telephone follow-up was conducted within 3 months post-surgery to assess surgery- and radiotherapy-related complications. HRQoL was evaluated using the BREAST-Q BCS module and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. Statistical analyses were performed using SPSS 27.0. Among 102 enrolled patients, common complications included incision site sclerosis (84.3%), pain (58.8%) and skin indentation (44.1%). Severe complications such as infection (7.8%) and delayed healing (12.7%) were less frequent. Grade I-II acute radiation dermatitis occurred in 73.5% of patients. Univariate analysis revealed that larger applicator size was significantly associated with higher-grade skin toxicity, skin indentation and irritation (P<0.01). Older age was a risk factor for incision infection and delayed healing (P<0.05). Larger tumor size (T stage) adversely affected satisfaction with breasts and chest physical well-being scores (P<0.01). The study concluded that, in patients with early-stage breast cancer treated with BCS plus IORT, 3-month postoperative complications are predominantly mild localized tissue reactions with rare severe events. Applicator size, age and tumor stage are significantly associated with early complications and acute-phase QoL, informing preoperative counseling and perioperative management optimization. However, this study only reflects acute recovery outcomes; long-term follow-up of the cohort is ongoing to evaluate late toxicities, cosmetic results and sustained QoL.

Background:Adding immune checkpoint inhibitors (ICIs) to neoadjuvant chemotherapy (NAC) enhances systemic efficacy in triple-negative breast cancer (TNBC). However, its impact on the survival outcomes of axillary surgical de-escalation remains undefined. This study evaluates whether chemo-immunotherapy mitigates survival risks historically associated with omitting axillary lymph node dissection (ALND) for sentinel lymph node biopsy (SLNB) in clinically node-positive (cN+) disease. Methods:In this retrospective cohort study using the National Cancer Database (2018-2022), we identified women with cN1-3, cM0 TNBC who received NAC ± ICIs and achieved ypN0 (axillary pathological complete response), followed by axillary surgery (SLNB or ALND). Overall survival (OS) was evaluated using restricted mean survival time (RMST) and propensity score matching. Multivariable Cox models assessed the independent effect of surgical extent (SLNB vs. ALND) on OS. Results:Out of 1,315,170 breast cancer cases, 4,336 eligible patients were included. The therapeutic regimen significantly interacted with the survival impact of axillary de-escalation. With NAC alone, SLNB was independently associated with inferior OS compared to ALND [5-year OS: 83.0% vs. 87.8%, P = .027; adjusted hazard ratio (aHR)=1.63, 95% CI = 1.12-2.38, P = .01]. Strikingly, adding ICIs neutralized this disparity: in the NAC+ICI cohort, SLNB yielded OS comparable to ALND (5-year OS: 90.1% vs. 93.6%, P = .99; identical 48-month RMST), with no significant survival detriment in multivariable analysis (aHR=1.19, 95% CI = 0.54-2.61, P = .67). Conclusions:The enhanced systemic control conferred by ICIs appears to compensate for the reduced surgical clearance of the axilla when ALND is omitted, effectively mitigating the survival risks associated with omitting ALND in cN+ TNBC. These real-world findings suggest modern chemo-immunotherapy facilitates axillary de-escalation without compromising overall survival, establishing a compelling rationale for prospective clinical trials.

This file contains Supplementary Table 1, pertaining to the proteomic classification of RPPA antibodies

Objective:To investigate the relationship between the C-reactive protein-albumin-lymphocyte index (CALLY) and clinicopathological characteristics, as well as its prognostic value in stage III breast cancer patients. Methods:A retrospective analysis was conducted on the clinicopathological data of 187 stage III breast cancer patients who were treated in our hospital from 2010 to 2015. The optimal cut-off value for CALLY index was determined by ROC curve. Chi-square tests and Fisher's exact tests were used for intergroup analysis. Survival curves were plotted using Kaplan-Meier method, and comparisons between groups were made using Log Rank test. Univariate and multivariate analyses were performed using the COX regression model. A nomogram prediction model was constructed based on the results of multivariate analysis and validated using the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Results:According to ROC curve, the optimal cut-off value for CALLY was determined to be 0.10, dividing the patients into a low CALLY group (54 patients) and a high CALLY group (133 patients). CALLY was identified as a potential independent prognostic factor for stage III breast cancer patients. Patients with high CALLY values had longer survival time than those with low CALLY values (DFS: χ2 = 9.109, P = 0.0025; OS: χ2 = 5.637, P = 0.0176). The C-indices for the nomograms predicting DFS and OS were 0.692 (95% CI: 0.541-0.811) and 0.730 (95% CI: 0.586-0.838), respectively. The calibration curves showed excellent calibration performance for predicting 1-year and 3-year DFS and OS. Decision curve analysis revealed that the nomogram model had better clinical performance than the CALLY model in predicting 3-year, 5-year, and 10-year DFS and OS. Conclusion:CALLY index is a potential independent prognostic factor for stage III breast cancer patients. It provides new insights and methods for clinical diagnosis and treatment of breast cancer.

Background:Breast cancer is the most common malignancy and a leading cause of cancer-related deaths among women worldwide. Although treatment advances have improved outcomes, the 5-year survival rate for metastatic breast cancer remains low. Understanding the anatomical distribution, associated risks, and prognostic features of metastases in patients with newly diagnosed stage IV breast cancer is essential for improving clinical management. This study aims to comprehensively investigate these aspects using data from the SEER database. Methods:This study utilized a retrospective cohort design, examining data from the Surveillance, Epidemiology, and End Results (SEER) database. The investigation considered patients diagnosed with stage IV breast cancer from SEER database. Using logistic regression, odds ratios (ORs) were calculated to determine the risk of various metastases, stratified based on sociodemographic and clinicopathological variables. Survival analyses were executed with Kaplan-Meier methodology in tandem with Cox regression analyses. Results:Out of 356,789 breast cancer patients considered, 18,036 (5.06%) were diagnosed with de novo stage IV disease. Bone metastasis predominated with a composition ratio of 42.6%. Patients with the HR-/HER2+ subtype exhibited the highest metastasis incidence at the time of diagnosis, constituting 8.7% of the entire cohort. Male patients displayed heightened susceptibility to bone, lung, and brain metastases compared to female counterparts. Hispanic individuals exhibited the highest propensity for brain metastases. Relative to other subtypes, the HR-/HER2- patients were more inclined toward lung metastases. Those with bone metastasis had a median survival period of 27 months. Grade III patients with brain or liver metastases faced the most adverse prognoses. A comprehensive profile detailing metastasis patterns by demographics, tumor site and stage, biology, and treatment was presented. Conclusions:This study represents the most comprehensive analysis of metastasis' anatomical distribution and prognosis in breast cancer, offering invaluable insights into metastatic tendencies and characteristics.

Tall Cell Carcinoma with Reversed Polarity (TCCRP) is a rare and distinct subtype of invasive breast carcinoma, first described in 2003. It is histologically characterized by tall columnar epithelial cells with reversed nuclear polarity and shares morphological features with papillary thyroid carcinoma (PTC). However, its unique molecular signature, including IDH2 and PIK3CA mutations, differentiates it from other breast cancer subtypes. A retrospective systematic study of 91 published cases of TCCRP was conducted, including two cases from our institution. Clinical, pathological, molecular, and treatment-related data were collected and analyzed. Descriptive statistics and Kaplan-Meier survival analysis were employed to evaluate disease-free survival (DFS) and overall survival (OS). Subgroup analyses explored associations between clinical features, molecular markers, and outcomes. The median age at diagnosis was 64 years, with a predominance of small tumors (mean size: 10.4 mm, T1 stage). Histologically, hallmark features included reversed nuclear polarity (100 %), nuclear grooves, and intranuclear pseudoinclusions. Immunohistochemical analysis confirmed a triple-negative profile (ER-/PR-/HER2-) in most cases, with consistent breast-specific marker expression (GATA3, CK7). Molecular testing revealed frequent IDH2 R172 (84.6 %) and PIK3CA (72.5 %) mutations. Surgical management, predominantly breast-conserving surgery (BCS), was the primary treatment, with adjuvant therapies rarely utilized. At a median follow-up of 35.8 months, recurrence occurred in only 2.2 % of cases, and the overall survival rate was 100 %. TCCRP is a rare, low-grade breast cancer subtype with a favorable prognosis and low recurrence risk based on currently available data, but longer follow-up studies are needed to confirm this observation. Its distinct histological and molecular features enable accurate diagnosis and differentiation from other breast cancers and metastatic thyroid carcinoma. Given its indolent nature, conservative treatment strategies, including BCS, are effective, and adjuvant therapies can be minimized. Future research should explore targeted therapies for IDH2 and PIK3CA mutations to expand treatment options for this unique subtype.