Background and purpose:Immune checkpoint blockade(ICB)has become a promising strategy for treating cervical cancer(CC),but terminal T cell depletion still limits the therapeutic efficacy of ICB.The deletion of sorting nexin-9(SNX9)can inhibit thymocyte selection-associated high mobility group box protein(TOX),alleviate T cell exhaustion,and provide new ideas for preventing T cell exhaustion and enhancing the efficacy of cancer immunotherapy.Therefore,this study aimed to explore the immune escape mechanism mediated by the depletion of CD8+T cells induced by the SNX9/TOX signaling pathway in the CC microenvironment.Methods:Fifty-four peripheral blood samples were collected,including 18 from CC patients,18 from patients with high-grade squamous intraepithelial lesions(HSIL)and 18 from subjects with normal cervix.In addition,the study collected 153 pairs of CC and adjacent tissues from patients who received operation in our hospital for the first time.Clinicopathological features,tumor stages,follow-up records and other relevant clinicopathological data of CC patients were obtained from hospital records.The research was approved by the ethics committee of Changsha Fourth Hospital(approval number:20220206).A total of 24 mice were randomly assigned to the following four groups:immunoglobulin G(IgG)group,Anti-SNX9 group,Anti-programmed death-1(PD-1)group and Anti-SNX9+Anti-PD-1 group,with 6 mice in each group.Each group received intraperitoneal injection of blocking antibody and isotype control treatment respectively.ELISpot was used to detect the ability of CD8+T cells to secrete tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ).The expressions of TOX and SNX9 in cervical cancer tissues were detected by western blot and immunohistochemistry.Results:The expressions of SNX9 and TOX mRNA in peripheral blood mononuclear cell(PBMC)of CC patients were higher compared with HSIL and normal controls(P＜0.05).The positive cell level of SNX9 and TOX immunohistochemical score were higher in CC tissue than in adjacent tissues(t=18.63,21.10,P＜0.001).The high expression of SNX9 in CC was related to low differentiation/undifferentiation,tumor size,parauterine infiltration,vaginal infiltration,late FIGO stage and pelvic lymph node metastasis(P＜0.05).Compared with the low expression group of SNX9,the overall survival time of CC patients in the high expression group of SNX9 was shorter(P＜0.05).The percentage of CD8+SNX9+T cells was significantly higher in CC patients than in normal controls and HSIL patients(P＜0.05).The ability of CD8+SNX9+T cells to secrete cytokines(TNF-α and IFN-γ)was significantly lower compared with CD8+SNX9-T cells(P＜0.05).Compared with the Anti-SNX9 group,the growth and proliferation of cervical tumor,the expression of SNX9 and TOX protein in tumor tissue in the Anti-SNX9+Anti-PD-1 group further decreased(P＜0.05),and the level of infiltrating CD8+T lymphocytes in tumor tissue and the ability of CD8+T lymphocytes to secrete functional factors TNF-α and IFN-γ further increased(P＜0.05).Conclusion:SNX9/TOX signaling pathway exhibits enhanced activity in patients with cervical cancer and mouse models,and is related to immunosuppression.Targeting SNX9/TOX signaling pathway may be a potential therapeutic strategy for CC.

Background and purpose:Accurate preoperative differentiation between vagal nerve cervical schwannomas(SCCS)and sympathetic chain cervical schwannomas(SCCS)in the neck is crucial because of their different postoperative complication.This study aimed to construct and validate a Diagnosis Score and vascular displacement nomogram for the preoperative differentiation of VNCS from SCCS in the neck.Methods:This cross-sectional study retrospectively analyzed patients with pathologically confirmed VNCS and SCCS at Fudan University Shanghai Cancer Center from January 2017 to April 2022.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(approval number:1612167-18).Inclusion criteria:① histopathological diagnosis of VNCS or SCCS through biopsy or surgical resection;② patients with complete clinic data;③availability of preoperative contrast-enhanced computed tomography(CT)or magnetic resonance imaging(MRI)examinations.Patients were excluded for:① contrast agent contraindications;② poor image quality;③ severe artifacts;④ non-standard scanning protocols.The cohort was randomly divided into training and validation sets in a 7∶3 ratio.Two radiologists(one resident and one attending physician)independently evaluated tumor characteristics(location,size and vascular displacement patterns)on preoperative imaging.Independent predictors were selected using LASSO regression analysis to construct a diagnostic scoring system and nomogram,with model performance evaluated by the receiver operating characteristic(ROC)curve.Results:A total of 110 patients were enrolled,with 77 cases allocated to the training set and 33 cases to the validation set.The age range was 24-78 years,and the mean age was(51.22±12.36)years.There were no statistically significant differences in baseline characteristics including age,gender,tumor location and size between the two patient groups(P＞0.05).ICA/ECA splaying was significantly associated with SCCS(P＜0.001),while the ICA/IJV splaying was significantly associated with VNCS(P＜0.001).Lateral and posterior ICA displacement were significantly associated with SCCS(P＜0.001),and medial and anterior ICA displacement were significantly associated with VNCS(P＜0.001).Five features including tumor size,ICA displacement direction,IJV displacement direction,ICA/ECA splaying and ICA/IJV splaying were used to establish the Diagnosis Score and nomogram.The nomogram combined imaging features showed favorable preference value for differentiating VNCS from SCCS,with area under curve(AUC)values of 0.953(95%CI:0.912-0.994)and 0.939(95%CI:0.885-0.993)for the training and validation cohorts,respectively.Conclusion:The Diagnosis Score and vascular displacement nomogram showed favorable predictive efficacy for differentiating VNCS from SCCS in the neck,and might be useful for clinical decision-making.

Breast cancer remains one of the frequently diagnosed malignant tumors among Chinese women,with hereditary cases accounting for 5%-10%of all diagnoses,where BRCA1/2 gene mutations serve as the primary genetic predisposition factors.Although targeted therapies like poly(ADP-ribose)polymerase(PARP)inhibitors have significantly improved prognoses for patients with BRCA-mutated breast cancer in recent years,critical clinical challenges persist,including the standardization of genetic testing protocols,optimization of precision treatment approaches,and refinement of long-term management strategies.In response to these challenges,our expert panel has conducted a comprehensive update to the 2018 Edition of this consensus by integrating the latest global evidence-based medical research with China's unique clinical practice characteristics.This 2025 Edition provides systematic evaluations and recommendations on five key aspects:indications for BRCA1/2 gene testing,testing methodologies,result interpretation,treatment strategies,and risk management.The main updates include:① Increasing the relationship between BRCA1/2 gene mutations and programmed death ligand-1(PD-L1)expression,as well as related content on BRCAness types;② Standardizing the application of genetic testing,such as increasing the significance,timing,and sample selection of clinical testing,and optimizing the BRCA testing population;③ Updating treatment strategies,such as non-drug treatment of BRCA1/2 gene mutation,treatment of triple negative breast cancer(TNBC)patients with BRCA1/2 gene mutation,treatment decisions of hormone receptor(HR)+/human epidermal growth factor receptor 2(HER2)-breast cancer patients with BRCA1/2 gene mutation,clinical use of PARP inhibitors and adverse reaction management;④ Addion of relevant content on long-term risk management,such as covering follow-up management,indications for preventive surgery,quality control and requirements for new genetic testing,updating genetic testing processes,report content and interpretation.This consensus aimed to establish standardized diagnostic and therapeutic frameworks for clinicians,advance precision medicine in BRCA-mutated breast cancer,and ultimately improve patient survival outcomes.As new evidence emerges,continuous updates will be implemented to incorporate the latest research findings.This consensus has been registered on the Practice guideline REgistration for transPAREncy(PREPARE)platform(registration number:PREPARE-2025CN1085).

Gastric cancer is a highly prevalent and aggressive malignancy worldwide,with generally poor prognosis.There are differences in epidemiology,clinicopathological characteristics,treatment modalities,and drug selection for gastric cancer between Eastern and Western populations.Recent advancements in targeted therapy and immunotherapy,the maturation of precision treatment concepts,and the promotion of multidisciplinary therapy have led to continuous updates in clinical research outcomes.Gastric cancer guidelines are annually updated to meet evolving diagnostic and therapeutic needs.This article compared the latest versions of three authoritative global gastric cancer guidelines[National Comprehensive Cancer Network(NCCN)clinical practice guidelines for gastric cancer 2024 version 5,European Society for Medical Oncology(ESMO)online guidelines for gastric cancer 2024,and Chinese Society of Clinical Oncology(CSCO)guidelines for gastric cancer diagnosis and treatment 2024],focusing on clinical treatment strategies for unresectable locally advanced or metastatic esophagogastric junction/gastric adenocarcinoma,and on the whole-process management and precise implementation guided by targets such as human epidermal growth factor receptor 2(HER2)expression,programmed cell death ligand 1(PD-L1)expression,mismatch repair(MMR)status,,and novel targets such as Claudin 18.2.Meanwhile,HER2-positive advanced gastric cancer has entered the era of full-line anti-HER2 treatment.Anti-HER2 antibody-drug conjugates(ADCs)has become a new option after first-line trastuzumab resistance.Immunotherapy combined with chemotherapy is regarded as a new standard for the first-line treatment of advanced gastric cancer.The diagnosis and treatment mode based on MMR status and PD-L1 expression promote the precision of immunotherapy.However,the detection of PD-L1 expression has difficulties in clinical promotion and implementation.The three guidelines in 2024 integrate the latest clinical study results,the new indication approval and the updated health care system.In particular,the CSCO gastric cancer guidelines are rewritten based on the rapid development of independently developed drugs in China and the approval of new indications.The three guidelines differ in the recommendation and adoption of targeted therapy and immunotherapy.This article showed different perspectives and focuses based on different guidelines,enriched the dimensions of clinical decision-making,helped the clinical adaptability of evidence-based guidelines to better enlightens clinical practice.

The diagnosis rate of early breast cancer has significantly increased with the proliferation of tumor screening and heightened health awareness.Clinical research,as the evidence base for guidelines and consensus,provides optimized treatment plans for breast cancer.This article summarized and classified several pivotal clinical studies that changed the clinical practice of early breast cancer,according to updates in domestic and international guidelines and consensus from 2023 to 2024.These included the optimization of neoadjuvant and adjuvant therapies,the escalation of adjuvant endocrine therapy,the optimization of local treatment,and attention to quality of life,etc.In the optimization of neoadjuvant and adjuvant therapies,the KEYNOTE-522 study established the therapeutic role of pembrolizumab combined with chemotherapy in early high-risk triple-negative breast cancer(TNBC).The FDChina study confirmed the non-inferiority of the subcutaneous formulation of trastuzumab combined with pertuzumab(H+P)in neoadjuvant treatment of human epidermal growth factor receptor 2(HER2)-positive breast cancer,offering a more convenient administration method.The KATHERINE study clarified the adjuvant role of trastuzumab emtansine(T-DM1)in HER2-positive breast cancer patients who did not achieve a pathologic complete response(pCR)after neoadjuvant therapy.In the escalation of adjuvant endocrine therapy,the MonarchE and NATALEE studies confirmed the efficacy of abemaciclib and ribociclib combined with endocrine therapy in high-risk hormone receptor(HR)-positive HER2-negative early breast cancer patients,promoting the application of cyclin-dependent kinase(CDK)4/6 inhibitors in early breast cancer treatment.In the optimization of local treatment,the ACOSOG Z11102 study supported the feasibility of breast-conserving surgery for multicentric breast cancer,the SENOMAC study provided evidence for exempting sentinel lymph node(SLN)low-burden breast cancer patients from axillary lymph node dissection(ALND),the SOUND study supported the exemption of sentinel lymph node biopsy(SLNB)for T1 and cN0 breast cancer patients,and the ICARO study suggested the feasibility of exempting ALND for patients with isolated tumor cells(ITCs)found after neoadjuvant chemotherapy with SLNB or targeted axillary dissection(TAD).The NSABP B-51/RTOG 1304 study provided a basis for the de-escalation of regional lymph node irradiation(RNI)and local treatment in ypN0 breast cancer after neoadjuvant therapy.In terms of quality of life and chemoprevention,the POSITIVE study proposed a protocol for pausing endocrine therapy for breast cancer patients with fertility needs,and the TAM-01 and IBIS-Ⅱ studies provided strong evidence-based medical evidence for chemoprevention in high-risk breast cancer patients.These pivotal clinical studies have profoundly impacted the clinical practice of early-stage breast cancer,not only optimizing treatment plans but also focusing on the quality of life and disease prevention of breast cancer patients.This article discussed the impact of the aforementioned clinical studies on the clinical practice of early breast cancer,centered on updates to various domestic and international breast cancer diagnosis and treatment guidelines and consensus.

Breast cancer is the most prevalent malignant tumor that poses a threat to women's health in China,with incidence and mortality rates persistently increasing.Given this critical situation,there is an urgent need to optimize therapeutic options through basic translational research to address current treatment challenges.This article provided a comprehensive overview of the significant advancements in fundamental translational breast cancer research in China over the past five years,aiming to provide a scientific basis and new directions for precision treatment of breast cancer.This research encompasses a range of subjects,including molecular typing,biomarker identification,exploration of drug resistance mechanisms,optimization of precision treatment strategies,and identification of new targets in breast cancer.In the domain of molecular typing,researchers have revealed substantial disparities in treatment responses among distinct subtypes of breast cancer through in-depth analysis.This has led to the proposal of specific therapeutic strategies for each subtype,thereby establishing a robust theoretical foundation for individualized treatment approaches.The identification of biomarkers plays a pivotal role in selecting appropriate treatment options for patients.Recent research advancements have demonstrated the potential of liquid biopsy and proteomics technologies in uncovering promising biomarkers,offering novel prospects for the early diagnosis and prognostic assessment of breast cancer.In the investigation of resistance mechanisms,researchers have elucidated the molecular underpinnings of resistance to endocrine therapy and human epidermal growth factor receptor 2(HER2)-targeted therapy and proposed potential strategies to overcome resistance.This has paved the way for novel approaches to enhance therapeutic efficacy.In the context of immunotherapy and targeted therapies,the discernment of novel targets and biomarkers has facilitated novel perspectives on breast cancer treatment.Based on advanced comprehension of tumor heterogeneity,researchers constantly optimize precision treatment strategies through multiomics analysis,thus offering patients with breast cancer enhanced personalized treatment options.Concurrently,the implementation of novel technologies has been instrumental in facilitating the advancement of precision treatment for breast cancer.For instance,the application of artificial intelligence technology has demonstrated considerable potential in the early screening,diagnosis,efficacy assessment and prognosis prediction of breast cancer.Conversely,the advent of innovative drug delivery systems facilitated by nanotechnology has led to enhanced targeting and efficacy of pharmaceutical agents.Furthermore,research into hydrogel patch technology and tumor vaccines has yielded novel strategies for the treatment of breast cancer.Overall,China has accomplished remarkable achievements in the field of basic translational research on breast cancer.These findings not only enhance our understanding of the molecular mechanisms of breast cancer,but also provide new directions and hope for the development of future therapeutic strategies.With the advancement of multidisciplinary integration and the application of new emerging technologies,precision therapy is expected to provide more benefits to breast cancer patients.

Antibody-drug conjugates(ADCs)represent a breakthrough in precision therapy for breast cancer,offering a unique targeted drug delivery mechanism that enhances tumor selectivity while reducing the nonspecific toxicity associated with conventional chemotherapy.In recent years,the clinical applications of ADCs in breast cancer have expanded significantly,particularly in human epidermal growth factor receptor 2(HER2)-positive and HER2-low breast cancer,reshaping the therapeutic landscape.Trastuzumab emtanserin(T-DM1)was the first ADC drug to replace lapatinib plus capecitabine as a second-line treatment for HER2-positive breast cancer,while trastuzumab deruxtecan(T-DXd)demonstrated remarkable efficacy in HER2-low breast cancer in the DESTINY-Breast04 trial,becoming the first approved ADC for this patient subgroup.Furthermore,trophoblast cell surface antigen 2(Trop-2)-targeting ADCs,such as sacituzumab govitecan(SG),have shown promising clinical benefits in patients with triple-negative breast cancer(TNBC)and hormone receptor-positive/HER2-negative breast cancer.Advances in next-generation ADC technologies,including improvements in linker stability,drug-to-antibody ratio(DAR)optimization,and enhanced bystander effects,have further improved the therapeutic efficacy and safety profile of these agents,reinforcing their role in the precision treatment of breast cancer.Although ADCs have demonstrated substantial clinical benefits,they are associated with target-and payload-related toxicities.However,with ongoing advancements in management strategies,their safety profile has been significantly improved.HER2-targeting ADCs present specific adverse events,including interstitial lung disease(ILD)associated with T-DXd,thrombocytopenia,and liver function abnormalities observed with T-DM1,while Trop-2-targeting ADCs such as SG are linked to hematologic toxicity and gastrointestinal side effects.Notably,structural optimizations in next-generation ADCs have led to significant improvements in their safety profile.Early monitoring,individualized dose modifications,and supportive care measures have been shown to effectively reduce the incidence of severe adverse events.Clinical studies indicate that toxicity management strategies for ADCs have matured,with most adverse effects being effectively controlled through optimized treatment regimens and adjunctive supportive care.Thus,in clinical practice,it is essential to consider patient-specific factors,prior treatment history,and comorbidities to devise an optimal ADC treatment strategy that maximizes both efficacy and safety.As ADC technology continues to evolve,breast cancer treatment is expected to become increasingly precise.The development of novel HER2-Trop-2 bispecific ADCs offers new therapeutic options for patients with HER2-low and HER2-negative breast cancer.Additionally,studies investigating the combination of T-DXd with immune checkpoint inhibitors(ICIs),CDK4/6 inhibitors,and poly(ADP-ribose)polymerase(PARP)inhibitors have demonstrated synergistic antitumor effects,further expanding the prospects for precision medicine in breast cancer.This review systematically summarized the latest advancements in ADCs for breast cancer,with a focus on the clinical applications,safety management strategies,and future development of HER2-and Trop-2-targeting ADCs,aiming to provide valuable insights for the future of precision breast cancer treatment.

Breast cancer,is the cancer type with highest incidence rate in women globally.To improve the treatment for breast cancer patients,Chinese scientists have done extensive research on breast cancer.Reviewing the progress made in 2024,Chinese scholars have achieved significant advancements in various aspects of breast cancer research.In the field of surgery,new optical imaging techniques have aided the accurate assessment of surgical margins,and targeted axillary dissection(TAD)continues to provide evidence-based support for de-escalation therapy in surgery.Radiomics combined with artificial intelligence(AI)also assists in surgical decision-making.In targeted therapy,tyrosine kinase inhibitors(TKIs)have shown excellent clinical outcomes.The PILHLE-001 study explored new subtypes for the use of pyrotinib,offering new therapeutic approaches for luminal/human epidermal growth factor receptor 2(HER2)low breast cancer.The efficacy and safety of anlotinib and apatinib are also reliable.Dual-targeted HER2 regimens in neoadjuvant therapy(NAT)and adjuvant therapy for early HER2-positive patients have demonstrated significant benefits over single-target regimens,improving survival rates.Various antibody-drug conjugates(ADCs)have shown significant clinical applicability,enhancing patient survival benefits,and novel drugs developed in China are making their way onto the international stage,increasing their global influence.Additionally,immunotherapy and precision treatment based on Fudan subtypes have shown varied degrees of survival improvement.In chemotherapy,different NAT strategies have been explored,offering more treatment options for doctors and patients.In endocrine therapy,the critical role of CDK4/6 inhibitors(CDK4/6i)in advanced hormone receptor positive/HER2-negative breast cancer has been further solidified,and issues concerning previously undetermined drug formulations of gonadotrophin releasing hormone analogue(GnRHa)have been examined.In radiotherapy,local radiotherapy combined with targeted therapy has significantly extended the survival of HER2-positive breast cancer patients with brain metastases,and optimizations have been made regarding the cardiotoxic side effects associated with radiotherapy.This article summarized the key clinical research on breast cancer in China in 2024,providing a reference for scholars and experts in related fields.

Breast cancer is one of the most prevalent malignant tumor in women worldwide,in which,triple-negative breast cancer(TNBC)is highly invasive and metastatic.In recent years,the incidence rate of TNBC has gradually increased and shown a trend of younger age.With the in-depth research on the molecular mechanism of breast cancer,neuropilin-1(NRP-1),a transmembrane protein,has been found to be associated with metastasis and prognosis of breast cancer,particularly TNBC.Therefore,NRP-1 has become a promising target for the diagnosis and treatment of breast cancer.The expression and distribution of NRP-1 in breast cancer can be detected by nuclear medicine,optical imaging and multimodal imaging methods in a non-invasive,real-time and accurate manner,which has significant application value in the early diagnosis,staging,treatment,and prognosis evaluation of breast cancer.Nuclear medicine probes specifically target tumor cells or tissues by combining radionuclides(e.g.,68Ga and 99mTc)with specific molecular ligands,and the signal is captured using positron emission tomography(PET)or single-photon emission computed tomography(SPECT),allowing for sensitive diagnosis of breast cancer.With the development of medical imaging and other interdisciplinary subjects,the NRP-1 targeted multimodal molecular probe[68Ga]Ga-NODAGA-K(Cy5)DKPPR combined the high sensitivity of PET with the high resolution advantage of near-infrared fluorescence(NIRF)to achieve precise diagnosis of breast cancer and provide real-time fluorescence navigation during surgery,enhancing the accuracy of tumor tissue identification and excision.In this paper,the advantages and disadvantages of NRP-1 targeted molecular probes in the diagnosis of breast cancer were systematically compared,and the application scope and latest research progress of various probes in the diagnosis and treatment of breast cancer were described,in order to provide reference for the development and clinical application of breast cancer targeted molecular probes.

With advancements in molecular biology research and precision medicine,treatment options for advanced breast cancer have become increasingly diverse.In 2024,significant research progress has been achieved across different molecular subtypes of advanced breast cancer.Endocrine therapy combined with cyclin-dependent kinase 4/6(CDK4/6)inhibitors has become the standard first-line treatment for hormone receptor-positive advanced breast cancer.Fulvestrant combined with abemaciclib serves as a treatment option after failure in CDK4/6 inhibitors.For patients with mutations in the AKT pathway,fulvestrant combined with the AKT inhibitor capivasertib provides significant long-term survival benefits.Trastuzumab deruxtecan(T-DXd)has emerged as a novel treatment option for patients with HER2 ultra-low expression.For HER2-positive advanced breast cancer,taxanes combined with trastuzumab and pertuzumab or pyrotinib remain the standard first-line treatments for trastuzumab-sensitive patients.The DESTINY-Breast07 trial evaluated the feasibility of using T-DXd as a first-line treatment,showing that whether used as monotherapy or in combination with pertuzumab,progression-free survival(PFS)was non-inferior to standard regimens reported in previous studies.For HER2-positive patients with brain metastases,updated results from the PERMEATE trial indicated that the combination of pyrotinib and capecitabine could provide overall survival benefits.The DESTINY-Breast12 trial demonstrated that T-DXd had similar antitumor activity against systemic and intracranial lesions,making it an effective treatment option for HER2-positive patients with brain metastases.Treatment strategies for advanced triple-negative breast cancer(TNBC)are shifting from conventional chemotherapy to regimens centered on chemotherapy combined with immunotherapy and antibody-drug conjugates(ADCs).The TORCHLIGHT trial showed that chemotherapy combined with the immune checkpoint inhibitor toripalimab improved the prognosis of patients with advanced TNBC.The NCC2167 trial found that when chemotherapy was combined with immunotherapy,metronomic chemotherapy offered superior efficacy and lower toxicity compared to conventional approaches.This article reviewed the significant research progress in advanced breast cancer in 2024.By summarizing related research data,it provides insights into the clinical experience of managing and making treatment decisions for patients with advanced breast cancer,serving as a reference for peers.Looking ahead,future clinical research should focus on individual differences among patients,tumor heterogeneity,and treatment resistance,aiming to improve treatment outcomes and the quality of life for patients with advanced breast cancer.