Introduction,Breast cancer is the most common cancer type in adolescents and young adults<40 years of age,accounting for 30%of cancers in this age group1.Breast cancer in the young presents significant challenges f...Introduction,Breast cancer is the most common cancer type in adolescents and young adults<40 years of age,accounting for 30%of cancers in this age group1.Breast cancer in the young presents significant challenges for patients and society,including more aggressive tumor biology,poor prognosis,genetic susceptibility,fertility preservation,and complex psychosocial issues.Moreover,because of the markedly younger median age of breast cancer,the proportion of young breast cancer patients in China is significantly higher than Western countries2.The first Young Breast Cancer in China(YBCC)consensus meeting was held in Guangzhou,China in December 2021 to address exclusive challenges and requirements facing young patients with breast cancer.Chinese medical experts from multiple specialties had an extensive discussion and formulated a consensus over several hot topics in young patients with breast cancer.The“Expert Consensus on the Diagnosis and Treatment of Young Breast Cancer in China(2022 edition)”published in the Chinese Medical Journal has garnered significant attention3,highlighting enormous interest in the YBCC consensus in the medical community and public.展开更多
Breast cancer(BC)remains the most frequently diagnosed malignancy worldwide,with an estimated 2.3 million new cases and approximately 685,000 deaths reported in 2020.Forecasts suggest a substantial rise in global inci...Breast cancer(BC)remains the most frequently diagnosed malignancy worldwide,with an estimated 2.3 million new cases and approximately 685,000 deaths reported in 2020.Forecasts suggest a substantial rise in global incidence,with new annual cases projected to reach 3.2 million by 2050,representing a 39%increase.Additionally,BC is expected to account for approximately 7.7%of the anticipated$25.2 trillion global economic burden associated with cancer by 2050.These trends underscore an urgent need for affordable,widely accessible and effective therapeutic strategies,particularly in low-and middle-income countries.Statins,commonly prescribed for the treatment of hypercholesterolaemia via inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A(HMG-CoA)reductase,have garnered increasing interest for their potential anticancer properties.This review focuses on the mechanistic underpinnings and therapeutic implications of statin use,particularly simvastatin,in the context of BC.Statins exert their primary effect through inhibition of the mevalonate pathway,which is crucial for cholesterol and isoprenoid biosynthesis.Disruption of this pathway impairs the prenylation of key signalling proteins,including members of the Ras and Rho GTPase families,which are essential for cancer cell proliferation,survival and metastasis.Preclinical evidence has demonstrated that simvastatin can induce tumour cell apoptosis,arrest cell-cycle progression and inhibit oncogenic signalling pathways.These effects have been particularly pronounced in hormone receptor-negative and triple-negative breast cancer(TNBC)subtypes,which are often associated with poor prognosis and limited treatment options.Epidemiological and observational studies further support a potential association between statin use and reduced BC recurrence and mortality.Nevertheless,robust evidence from randomised controlled trials remains limited,and further investigation is required to establish causality and define optimal therapeutic regimens.Given their well-established safety profile,global accessibility and pleiotropic effects,statins,especially simvastatin,represent a promising class of repurposed drugs in the adjuvant treatment of BC.This review synthesises evidence from the past two decades,highlighting the need for continued clinical research to validate and optimise the use of statins as adjunctive agents in BC therapy.展开更多
Breast cancer remains a global health challenge with greater than 2.3 million new cases diagnosed annually 1,according to the World Health Organization1.Management of breast cancer is shaped by a complex interplay of ...Breast cancer remains a global health challenge with greater than 2.3 million new cases diagnosed annually 1,according to the World Health Organization1.Management of breast cancer is shaped by a complex interplay of international guidelines,regional adaptations,and the rapidly evolving fields of precision medicine and artificial intelligence(AI).展开更多
Background:Sclerosing adenosis(SA)and breast cancer(BC)often exhibit overlapping clinical,imaging,and pathological characteristics,making them difficult to differentiate.SA may also coexist with BC(SA+BC),including du...Background:Sclerosing adenosis(SA)and breast cancer(BC)often exhibit overlapping clinical,imaging,and pathological characteristics,making them difficult to differentiate.SA may also coexist with BC(SA+BC),including ductal carcinoma in situ(SA-DCIS)and invasive breast cancer(SA-IBC),which complicates diagnosis even when core-needle biopsy(CNB)suggests SA.This study aimed to develop interpretable AI-based binary and ternary classification models that leverage clinical and imaging features to distinguish SA-only from SA+BC and to further differentiate among SA-only,SA-DCIS,and SA-IBC.Methods:We retrospectively analyzed a cohort of 726 patients with SA(January 2006 to December 2021),comprising 537 SA-only and 189 SA+BC cases(90 SA-DCIS,99 SA-IBC).Multiple machine learning algorithms-logistic regression,support vector machine,decision tree,XGBoost,and random forest-were compared using AUC,accuracy,F1-score,and C-index.Model interpretability was assessed with SHAP to elucidate feature contributions and identify key predictors.Additionally,we incorporated an independent external validation cohort consisting of 113 patients to verify the model's effectiveness.展开更多
The landscape of breast cancer treatment has undergone a transformative shift with the integration of immunotherapy.Historically considered a“cold”tumor with limited immunogenicity,breast cancer management was domin...The landscape of breast cancer treatment has undergone a transformative shift with the integration of immunotherapy.Historically considered a“cold”tumor with limited immunogenicity,breast cancer management was dominated by surgery,chemotherapy,radiotherapy,and targeted therapies1.However,the advent of immune checkpoint inhibitors(ICIs)has challenged this paradigm,opening a new frontier.The initial breakthrough in triple-negative breast cancer(TNBC)demonstrated that a subset of patients could derive profound and durable clinical benefit from pembrolizumab and atezolizumab2,3.Today,precision immunotherapy aims to identify the patients most likely to respond,to convert immunologically silent tumors into responsive tumors,and to strategically combine immunotherapies with other modalities to overcome resistance.This evolution from empirical application to biomarker-driven strategies marks the critical juncture at which we stand,transitioning promising clinical trial data into refined,effective,and accessible clinical practice4.Recent key clinical studies on breast cancer immunotherapy are summarized in Table 1.展开更多
Neoadjuvant therapy(NAT)has become the standard treatment for patients with locally advanced breast cancer and stage II-III HER2-positive(HER2+)or triple-negative breast cancer(TNBC)1,2.It is essential to accurately m...Neoadjuvant therapy(NAT)has become the standard treatment for patients with locally advanced breast cancer and stage II-III HER2-positive(HER2+)or triple-negative breast cancer(TNBC)1,2.It is essential to accurately mark the primary breast tumor and positive axillary lymph nodes(ALNs)prior to NAT to ensure precise surgical excision,guide axillary downstaging,and guarantee reliable lesion retrieval for pathologic evaluation3.The false-negative rate of sentinel lymph node biopsy(SLNB)after NAT can be reduced to<10%by applying modalities,such as the identification of≥3 sentinel lymph nodes(SLNs)with dual-mapping techniques or removal of the marked lymph node with target axillary dissection(TAD)according to the ASCO,NCCN,and CBCS guidelines3-5.However,there is a lack of consensus regarding the optimal methods and materials for accurate marking6,7.Conventional techniques include clip placement,guidewire localization,and carbon or ink tattooing,whereas wireless technologies,such as MagseedR,radiofrequency identification tags,SAVI SCOUTR,and radioactive iodine-125(125I)seeds,have also been adopted.Traditional marking techniques have a localization failure rate of approximately 10%.In contrast,the use of 125I seeds(with a radiation dose of 0.1-0.3 mCi)has significantly improved localization accuracy8,9.Nevertheless,owing to radioactive properties,concerns have been raised regarding the potential impact of 125I seed marking on assessing the pathologic complete response(pCR)after NAT10.Moreover,whether the influence of 125I seed marking on pCR could lead to suboptimal adjuvant treatment decisions and potentially compromise long-term oncologic outcomes has not been established.To investigate the potential impact of 125I seed placement on the pCR rate and long-term outcomes in breast cancer patients receiving NAT,we conducted a retrospective cohort study utilizing propensity score matching(PSM).展开更多
Breast cancer stands as the most prevalent malignancy among women worldwide and a leading cause of cancer-related mortality,posing a persistent challenge to global public health1.In recent decades,the landscape of bre...Breast cancer stands as the most prevalent malignancy among women worldwide and a leading cause of cancer-related mortality,posing a persistent challenge to global public health1.In recent decades,the landscape of breast cancer care has been profoundly reshaped by the rapid development of precision medicine,targeted therapy,immunotherapy,and clinical translational research.展开更多
Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance pati...Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance patients remains limited.This study examined real-world outcomes of palbociclib plus endocrine therapy in Asian patients,with additional subgroup analyses by age and performance status.Methods:We retrospectively analyzed 46 consecutive Asian patients with recurrent or de novo HR+/HER2−breast cancer treated with first-line palbociclib plus ET between April 2021 and March 2025.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall response rate(ORR),disease control rate(DCR),and safety.Subgroup analyses were performed by age(<70 vs.≥70 years)and performance status(PS;0–1 vs.2–3).Results:The median PFS was 26.6 months(range,1.4–69.5).Stratified by age,median PFS was 26.9 months in patients<70 years and 26.2 months in those≥70 years(p=0.760).By PS,PFS was 26.9 months for PS 0–1 and 17.8 months for PS 2–3(p=0.099).ORR was 60.9%and DCR 93.5%;notably,all PS 2–3 patients achieved disease control.Hematologic toxicities were common,with neutropenia(80.4%)and leukopenia(86.7%)predominating,but grade≥3 anemia was rare(2.2%).Elderly patients experienced anemia more frequently,while overall toxicity remained manageable.Dose reductions occurred in 47.8%without loss of efficacy.Conclusions:In routine Japanese practice,palbociclib plus ET provided prolonged PFS and high disease control consistent with pivotal trials and international real-world evidence.Importantly,elderly patients tolerated treatment well,and selected PS 2–3 patients also derived clinical benefit.These findings indicate that neither age nor PS alone should preclude the use of palbociclib in carefully monitored real-world patients.展开更多
Objective:To investigate the long-term prognosis and postoperative cosmetic outcomes of breast-conserving surgery combined with sentinel lymph node biopsy in patients with early-stage breast cancer,providing a referen...Objective:To investigate the long-term prognosis and postoperative cosmetic outcomes of breast-conserving surgery combined with sentinel lymph node biopsy in patients with early-stage breast cancer,providing a reference for the selection of clinical treatment plans.Methods:A retrospective analysis was conducted on the clinical data of 68 patients with early-stage breast cancer admitted from January 2022 to December 2025.Based on the surgical approach,patients were divided into an observation group(breast-conserving surgery+sentinel lymph node biopsy)and a control group(other surgical methods such as modified radical mastectomy/total mastectomy).Clinical and pathological characteristics,incidence of postoperative complications,follow-up prognosis,and satisfaction with cosmetic outcomes were compared between the two groups.Results:Among the 68 patients,41 were in the observation group and 27 in the control group.The average age of patients in the observation group was(54.32±8.15)years,while that in the control group was(62.45±9.76)years.The average tumor size in the observation group was(1.86±0.72)cm,compared to(3.21±1.45)cm in the control group.The incidence of postoperative complications in the observation group was 9.76%,significantly lower than that in the control group at 33.33%(P<0.05).The 6-month disease-free survival rate was 95.12%in the observation group and 88.89%in the control group,with no statistically significant difference between the two groups(P>0.05).The excellent and good rate of cosmetic outcomes in the observation group was 87.80%,significantly higher than that in the control group at 29.63%(P<0.05).Conclusion:Breast-conserving surgery combined with sentinel lymph node biopsy for early-stage breast cancer can achieve long-term prognostic outcomes comparable to those of traditional radical surgery,with the advantages of fewer postoperative complications and superior cosmetic results.This approach is worthy of clinical promotion and application,particularly for early-stage breast cancer patients who have a demand for preserving breast morphology.展开更多
BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probi...BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.展开更多
Breast cancer is one of the most prevalent malignancies among women and comprises a heterogeneous spectrum of molecular subtypes with distinct biological behaviors.Among various regulatory molecules,sphingolipids play...Breast cancer is one of the most prevalent malignancies among women and comprises a heterogeneous spectrum of molecular subtypes with distinct biological behaviors.Among various regulatory molecules,sphingolipids play pivotal roles in dynamically modulating fundamental cellular processes such as proliferation,apoptosis,and metastasis through metabolic interconversions,including phosphorylation,glycosylation,and the generation of sphingosine-1-phosphate.This review aims to elucidate the mechanisms through which sphingolipid metabolism orchestrates cancer cell fate and drives breast cancer progression.Particular emphasis is placed on the balance between proapoptotic ceramides and pro-survival metabolites,such as sphingosine-1-phosphate,which collectively influence tumor growth and the therapeutic response.Additional sphingolipid species,including glucosylceramide and gangliosides(GD2,GD3,GM1,and GM3),have also been implicated in promoting breast cancer development.Furthermore,sphingolipid-based therapeutic strategies,including immunotherapy and antibody therapy,are discussed.By providing a comprehensive overview of sphingolipid metabolism,this review aims to identify novel therapeutic targets that may help overcome treatment resistance and improve clinical outcomes in breast cancer.展开更多
Background:As a heterogeneous disease,breast cancer requires refined classification frameworks that can effectively guide targeted therapies.However,traditional methods fail to capture the comprehensive molecular insi...Background:As a heterogeneous disease,breast cancer requires refined classification frameworks that can effectively guide targeted therapies.However,traditional methods fail to capture the comprehensive molecular insights needed for this purpose.Methods:To comprehensively capture breast cancer heterogeneity,we employed integrative clustering that incorporates six molecular features from 670 breast cancer samples.Ten distinct clustering algorithms were combined to ensure robust subtype identification,and the identified subtypes were validated in four independent datasets.Subsequently,we constructed a survival support vector machine prognostic model based on key molecular features to enhance survival prediction and clinical applicability.Results:Five novel subtypes were identified:consensus subtypes 1–5(CS1–CS5).CS2 was an aggressive subtype with elevated TP53 mutation rates,high tumor mutational burden,and strong sensitivity to YM-155 and ispinesib.Conversely,CS5 exhibited stable genomics with enhanced nucleotide excision repair and favorable prognoses.CS2 and CS4 showed enriched immune checkpoint expression,indicating potential immunotherapy responsiveness,while CS1 and CS5 exhibited immune-cold profiles.The survival support vector machine model effectively predicted survival outcomes across independent datasets.Conclusions:The refined breast cancer classification framework developed in this research uncovers new insights into molecular heterogeneity,enhances risk stratification,and enables the identification of promising therapeutic targets.The potential of this framework to optimize personalized treatment strategies warrants further clinical validation.展开更多
Breast cancer is the most common malignant tumor among women globally and poses a major public health challenge due to limitations in traditional diagnostic and treatment processes,such as subjective interpretation bi...Breast cancer is the most common malignant tumor among women globally and poses a major public health challenge due to limitations in traditional diagnostic and treatment processes,such as subjective interpretation biases and inefficient multidimensional data integration.Artificial intelligence(AI),particularly deep learning and machine learning technologies,has emerged as a transformative tool in addressing these issues.Clinically,AI has been widely applied in imaging screening to improve detection rates and reduce reading time,digital pathology for precise tumor typing and gene mutation prediction,treatment decisionsupport systems to enhance guideline compliance,and drug research and development to accelerate target identification and virtual screening.Despite these achievements,AI implementation faces challenges,such as data standardization issues,limited model generalization,low clinical accessibility,and unclear ethical-legal responsibilities,which require targeted solutions that include national data standards,multi-center training,hierarchical physician training,and explainable AI.Future directions involve multimodal data integration,human-AI collaborative multidisciplinary team models,and extension to full-cycle health management from prevention-to-rehabilitation.This review provides a systematic overview of the role of AI in breast cancer care,offering insights for clinical practice and scientific research innovation,and supporting the transition toward personalized and intelligent medicine in oncology.展开更多
Objectives:Vascular endothelial growth factor(VEGF)regulates tumor vascularization in response to hypoxia and inflammatory signals.The polyphenol curcumin is supposed to interfere with inflammation-induced VEGF secret...Objectives:Vascular endothelial growth factor(VEGF)regulates tumor vascularization in response to hypoxia and inflammatory signals.The polyphenol curcumin is supposed to interfere with inflammation-induced VEGF secretion and might therefore support anti-VEGF-based treatments.We aimed to investigate the interaction between curcumin and the inflammatory cytokine Interleukin-1β(IL-1β)for VEGF secretion in breast cancer cell lines representing major breast cancer subtypes.Methods:VEGF in cell cultures was detected by Western blot and enzyme-linked immunosorbent assay(ELISA).Kinase phosphorylation was investigated by Western blotting.Gene expressions were analyzed by correlation tests.VEGF was evaluated in a retrospective breast cancer cohort by immunohistochemistry.Survival analysis was performed by the Kaplan-Meier algorithm.Results:VEGF secretion and kinase signaling in response to IL-1βand curcumin varied significantly for the cell lines MCF-7(Luminal A),SK-BR-3(HER2/neu+),MDA-MB-231,and UACC-3199(triple negative breast cancer).All cell lines increased VEGF secretion under hypoxia,but IL-1βincreased VEGF secretion only in MCF-7 cells.Curcumin inhibited VEGF secretion in MDA-MB-231,but increased it in MCF-7 and UACC-3199 cells.Curcumin induced phosphorylation of extracellular signal-regulated kinase(ERK)and p38-mitogen-activated protein kinase(p38-MAPK).However,inhibitor experiments demonstrated that ERK was more important for VEGF secretion.In gene expression data from the METABRIC study,no clear correlation of hypoxia-induced factor(HIF1A),IL-1β,and VEGF mRNA expression was observed;however,a suggested crosstalk of hypoxia and inflammatory pathways was observed.Conclusion:These dissimilar responses of breast cancer cell lines suggest that therapy efficiency with anti-VEGF,anti-IL-1β,or curcumin will also vary within breast cancers.展开更多
Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strateg...Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strategies imperative.Although elevated expression of discs large homolog 3(DLG3)has been reported in BRCA,its functional role in disease progression remains unclear.We performed bioinformatic analyses of clinical datasets to evaluate the prognostic significance of DLG3 expression in BRCA patients.In vitro gain-and loss-of-function experiments were conducted to assess the impact of DLG3 on BRCA cell proliferation,migration,and colony formation.Transcriptomic profiling,coupled with pharmacological inhibition,was employed to identify and validate downstream signaling pathways.Additionally,we extended our validation to an in vivo model to assess the role of DLG3 in tumor progression.We found that elevated DLG3 levels correlated with poor prognosis in breast cancer patients.Functionally,DLG3 overexpression significantly promoted cell proliferation and migration in estrogen receptor-positive MCF7 and triple-negative MDA-MB-231 breast cancer cells,whereas its knockdown suppressed these effects.Transcriptomic analyses revealed that DLG3 activates signal transducer and activator of transcription 3(STAT3)signaling,a finding further corroborated by Western blot.Critically,treatment with the STAT3 inhibitor Stattic attenuated DLG3-driven proliferation and migration,supporting a DLG3-STAT3 oncogenic axis.Furthermore,in vivo studies validated the role of DLG3 in promoting tumor growth and its correlation with elevated STAT3 signaling,consistent with our in vitro findings.Our findings establish DLG3 as a novel driver of breast cancer progression that directly activates STAT3 signaling.DLG3 thus represents both a potential prognostic biomarker and a promising therapeutic target for aggressive breast cancer subtypes,including triple-negative breast cancer.展开更多
Although the combination of chemotherapy and immunotherapy can improve the treatment of breast cancer,traditional drugs are highly toxic because they do not specifically target tumors.In this study,we developed a self...Although the combination of chemotherapy and immunotherapy can improve the treatment of breast cancer,traditional drugs are highly toxic because they do not specifically target tumors.In this study,we developed a self-driving bacteria/nanoparticle biohybrid called Bif@PDA-aPD1/DOX-Lip by attaching polydopamine(PDA)coated doxorubicin(DOX)liposomes and the immune checkpoint inhibitor anti-programmed cell death protein 1 antibody(aPD-1)to Bifidobacterium infantis(B.infantis,Bif).Using the homing abilities of bacteria,Bif@PDA-aPD1/DOX-Lip could actively accumulate in tumor tissue,releasing DOX and aPD-1 in the acidic environment to have a synergistic anti-tumor effect.Results show that the concentration of DOX in tumors of the Bif@PDA-aPD1/DOX-Lip group was 6.31 times higher than in the free DOX group.The combination of DOX and aPD-1 not only killed tumor cells but also promoted immune normalization by maturing dendritic cells(DCs),increasing M1 macrophage ratio,and enhancing infiltration of CD8^(+) and CD4^(+)T cells in tumors and spleen.Therefore,Bif@PDA-aPD1/DOX-Lip therapy significantly inhibited tumor growth and increased the average survival time of mice to over 80 days.The Bif@PDA-aPD1/DOX-Lip biomotors offer a highly effective method for enhancing chemo-immunotherapy in solid tumors.展开更多
Traditional artificial intelligence(AI)-based methods for breast cancer diagnosis often rely on a single modality,such as ultrasound images.With the rise of multimodal approaches,multiple data sources,including imagin...Traditional artificial intelligence(AI)-based methods for breast cancer diagnosis often rely on a single modality,such as ultrasound images.With the rise of multimodal approaches,multiple data sources,including imaging from diverse medical modalities,structured clinical information,and unstructured medical reports,are increasingly integrated to provide richer and more informative signals for model training.This survey reviews the data modalities employed in AI-based breast cancer research,examines common multimodal combinations and fusion strategies,and discusses their applications across clinical tasks such as diagnosis,treatment planning,and outcome prediction.By consolidating current literature and identifying critical gaps,this survey aims to guide future research toward the development of reliable,clinically relevant multimodal AI systems for use in breast cancer management.展开更多
Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabo...Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabolism,in the aggressiveness and metastatic behavior of BC.Methods:A comprehensive analysis was performed using in silico transcriptomic data(n=2509 patients),immunohistochemical profiling of BC tissues(n=103),and validation through western blotting in multiple BC cell lines.Gene expression and survival analyses were conducted using Tumor Immune Estimation Resource(TIMER),Gene Expression Profiling Interactive Analysis 2(GEPIA2),and the cBioPortal for cancer genomics(cBioPortal)platforms.Correlations between PNP and key epithelial–mesenchymal transition(EMT)markers,molecular subtypes,tumor grades,and stages were examined.Results:PNP was significantly overexpressed in human epidermal growth factor receptor 2(HER-2)-positive and triple-negative BCs compared to luminal subtypes.High PNP levels were strongly associated with advanced BC stages,high-grade tumors,EMT phenotypes,and poor overall survival.Notably,HER-2 inhibition suppressed PNP expression,while PNP gene silencing induced HER-2 upregulation,revealing a reciprocal regulatory loop.Dual inhibition of PNP and HER-2 resulted in a significant reduction in cell viability compared to HER-2 inhibition alone.Conclusion:Collectively,PNP emerges as a promising biomarker of BC aggressiveness and progression.Its reciprocal interaction with HER-2 underscores its potential as a therapeutic target.Dual targeting of PNP and HER-2 may offer a novel strategy for improving outcomes in aggressive BC subtypes.展开更多
Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis....Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis.Herein,the targeted theranostic platform of cysteine-modified gold nanodots-sulfhydrated luteinizing hormone releasing hormone(CGN-SLR)nanosystem was designed for target recognition and precise dual-mode imaging-guided photothermal therapy(PTT)against TNBC.On the one hand,the CGN-SLR nanosystem can serve as an ideal targeting fluorescent probe and computed tomography(CT)enhancer to facilitate the accurate diagnosis and surgical guidance of TNBC.On the other hand,the CGN-SLR nanosystem with great targeting and PTT ability can significantly inhibit the growth of TNBC,without causing harm to normal tissues and healthy organs.It provides an effective strategy for the diagnosis and treatment of TNBC through the rational design of multifunctional nanoplatform with target recognition,multiple imaging guidance/monitoring,and high-efficiency PTT.展开更多
Breast cancer exhibits profound biological and spatial heterogeneity,which contributes to variable responses to neoadjuvant chemotherapy(NAC)and challenges precision treatment planning.Radiomics,an emerging discipline...Breast cancer exhibits profound biological and spatial heterogeneity,which contributes to variable responses to neoadjuvant chemotherapy(NAC)and challenges precision treatment planning.Radiomics,an emerging discipline that converts standard medical images into high-dimensional quantitative data,offers a non-invasive and reproducible means to capture tumor phenotype,heterogeneity,and treatment-induced changes.This review provides a comprehensive overview of recent advances in radiomics for breast cancer NAC,emphasizing the roles in predicting a pathologic complete response(pCR),monitoring early therapeutic efficacy,and quantifying intratumoral heterogeneity.Among imaging modalities,magnetic resonance imaging(MRI)-based radiomics,particularly utilizing dynamic contrast-enhanced and diffusion-weighted sequences,demonstrates robust predictive performance for the pCR,with multi-center studies reporting area under the curve(AUC)values>0.80.Longitudinal and delta-radiomics approaches further enhance early response evaluation by tracking temporal alterations in imaging features that precede measurable morphologic regression.Radiomic assessment of tumor heterogeneity,especially in triple-negative breast cancer(TNBC),reveals strong associations with immune infiltration,metabolic reprogramming,and therapeutic resistance,providing mechanistic insight into radiomic biomarkers.Integrative multi-omics frameworks,combining radiomics with genomics,transcriptomics and pathomics,are increasingly elucidating the biological underpinnings of imaging phenotypes,improving both model interpretability and clinical relevance.Despite these advances,widespread clinical adoption of radiomics is limited by methodologic variability,lack of standardization,and insufficient external validation.Future efforts should focus on harmonized imaging protocols,explainable artificial intelligence,and prospective multi-center trials to translate radiomics into a clinically actionable tool.Collectively,radiomics represents a transformative approach for individualized response prediction and dynamic treatment optimization in precision breast cancer management(Figure 1).展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82230057 and 82272859)the National Key R&D Program of China(Grant No.2022YFC2505101).
文摘Introduction,Breast cancer is the most common cancer type in adolescents and young adults<40 years of age,accounting for 30%of cancers in this age group1.Breast cancer in the young presents significant challenges for patients and society,including more aggressive tumor biology,poor prognosis,genetic susceptibility,fertility preservation,and complex psychosocial issues.Moreover,because of the markedly younger median age of breast cancer,the proportion of young breast cancer patients in China is significantly higher than Western countries2.The first Young Breast Cancer in China(YBCC)consensus meeting was held in Guangzhou,China in December 2021 to address exclusive challenges and requirements facing young patients with breast cancer.Chinese medical experts from multiple specialties had an extensive discussion and formulated a consensus over several hot topics in young patients with breast cancer.The“Expert Consensus on the Diagnosis and Treatment of Young Breast Cancer in China(2022 edition)”published in the Chinese Medical Journal has garnered significant attention3,highlighting enormous interest in the YBCC consensus in the medical community and public.
基金supported by Rural Health Research Institute,Charles Sturt University.
文摘Breast cancer(BC)remains the most frequently diagnosed malignancy worldwide,with an estimated 2.3 million new cases and approximately 685,000 deaths reported in 2020.Forecasts suggest a substantial rise in global incidence,with new annual cases projected to reach 3.2 million by 2050,representing a 39%increase.Additionally,BC is expected to account for approximately 7.7%of the anticipated$25.2 trillion global economic burden associated with cancer by 2050.These trends underscore an urgent need for affordable,widely accessible and effective therapeutic strategies,particularly in low-and middle-income countries.Statins,commonly prescribed for the treatment of hypercholesterolaemia via inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A(HMG-CoA)reductase,have garnered increasing interest for their potential anticancer properties.This review focuses on the mechanistic underpinnings and therapeutic implications of statin use,particularly simvastatin,in the context of BC.Statins exert their primary effect through inhibition of the mevalonate pathway,which is crucial for cholesterol and isoprenoid biosynthesis.Disruption of this pathway impairs the prenylation of key signalling proteins,including members of the Ras and Rho GTPase families,which are essential for cancer cell proliferation,survival and metastasis.Preclinical evidence has demonstrated that simvastatin can induce tumour cell apoptosis,arrest cell-cycle progression and inhibit oncogenic signalling pathways.These effects have been particularly pronounced in hormone receptor-negative and triple-negative breast cancer(TNBC)subtypes,which are often associated with poor prognosis and limited treatment options.Epidemiological and observational studies further support a potential association between statin use and reduced BC recurrence and mortality.Nevertheless,robust evidence from randomised controlled trials remains limited,and further investigation is required to establish causality and define optimal therapeutic regimens.Given their well-established safety profile,global accessibility and pleiotropic effects,statins,especially simvastatin,represent a promising class of repurposed drugs in the adjuvant treatment of BC.This review synthesises evidence from the past two decades,highlighting the need for continued clinical research to validate and optimise the use of statins as adjunctive agents in BC therapy.
文摘Breast cancer remains a global health challenge with greater than 2.3 million new cases diagnosed annually 1,according to the World Health Organization1.Management of breast cancer is shaped by a complex interplay of international guidelines,regional adaptations,and the rapidly evolving fields of precision medicine and artificial intelligence(AI).
基金National High Level Hospital Clinical Research Funding,Grant/Award Numbers:2025-PUMCH-A-147,2022-PUMCH-B-039Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFM),Grant/Award Number:2021-I2M-1-014。
文摘Background:Sclerosing adenosis(SA)and breast cancer(BC)often exhibit overlapping clinical,imaging,and pathological characteristics,making them difficult to differentiate.SA may also coexist with BC(SA+BC),including ductal carcinoma in situ(SA-DCIS)and invasive breast cancer(SA-IBC),which complicates diagnosis even when core-needle biopsy(CNB)suggests SA.This study aimed to develop interpretable AI-based binary and ternary classification models that leverage clinical and imaging features to distinguish SA-only from SA+BC and to further differentiate among SA-only,SA-DCIS,and SA-IBC.Methods:We retrospectively analyzed a cohort of 726 patients with SA(January 2006 to December 2021),comprising 537 SA-only and 189 SA+BC cases(90 SA-DCIS,99 SA-IBC).Multiple machine learning algorithms-logistic regression,support vector machine,decision tree,XGBoost,and random forest-were compared using AUC,accuracy,F1-score,and C-index.Model interpretability was assessed with SHAP to elucidate feature contributions and identify key predictors.Additionally,we incorporated an independent external validation cohort consisting of 113 patients to verify the model's effectiveness.
基金supported by the Non-communicable Chronic Diseases National Science and Technology Major Project(Grant No.2025ZD0544003).
文摘The landscape of breast cancer treatment has undergone a transformative shift with the integration of immunotherapy.Historically considered a“cold”tumor with limited immunogenicity,breast cancer management was dominated by surgery,chemotherapy,radiotherapy,and targeted therapies1.However,the advent of immune checkpoint inhibitors(ICIs)has challenged this paradigm,opening a new frontier.The initial breakthrough in triple-negative breast cancer(TNBC)demonstrated that a subset of patients could derive profound and durable clinical benefit from pembrolizumab and atezolizumab2,3.Today,precision immunotherapy aims to identify the patients most likely to respond,to convert immunologically silent tumors into responsive tumors,and to strategically combine immunotherapies with other modalities to overcome resistance.This evolution from empirical application to biomarker-driven strategies marks the critical juncture at which we stand,transitioning promising clinical trial data into refined,effective,and accessible clinical practice4.Recent key clinical studies on breast cancer immunotherapy are summarized in Table 1.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82573747,82172873,W2421095,and 82503888)National Science and Technology Major Project(Grant No.2025ZD0543900)+2 种基金Natural Science Foundation of Shandong Province(Grant Nos.ZR2024LMB011 and ZR2024QH058)Taishan Scholars Program of Shandong Province(Grant No.tsqn202211337)Collaborative Academic Innovation Project of Shandong Cancer Hospital(Grant No.GF003).
文摘Neoadjuvant therapy(NAT)has become the standard treatment for patients with locally advanced breast cancer and stage II-III HER2-positive(HER2+)or triple-negative breast cancer(TNBC)1,2.It is essential to accurately mark the primary breast tumor and positive axillary lymph nodes(ALNs)prior to NAT to ensure precise surgical excision,guide axillary downstaging,and guarantee reliable lesion retrieval for pathologic evaluation3.The false-negative rate of sentinel lymph node biopsy(SLNB)after NAT can be reduced to<10%by applying modalities,such as the identification of≥3 sentinel lymph nodes(SLNs)with dual-mapping techniques or removal of the marked lymph node with target axillary dissection(TAD)according to the ASCO,NCCN,and CBCS guidelines3-5.However,there is a lack of consensus regarding the optimal methods and materials for accurate marking6,7.Conventional techniques include clip placement,guidewire localization,and carbon or ink tattooing,whereas wireless technologies,such as MagseedR,radiofrequency identification tags,SAVI SCOUTR,and radioactive iodine-125(125I)seeds,have also been adopted.Traditional marking techniques have a localization failure rate of approximately 10%.In contrast,the use of 125I seeds(with a radiation dose of 0.1-0.3 mCi)has significantly improved localization accuracy8,9.Nevertheless,owing to radioactive properties,concerns have been raised regarding the potential impact of 125I seed marking on assessing the pathologic complete response(pCR)after NAT10.Moreover,whether the influence of 125I seed marking on pCR could lead to suboptimal adjuvant treatment decisions and potentially compromise long-term oncologic outcomes has not been established.To investigate the potential impact of 125I seed placement on the pCR rate and long-term outcomes in breast cancer patients receiving NAT,we conducted a retrospective cohort study utilizing propensity score matching(PSM).
文摘Breast cancer stands as the most prevalent malignancy among women worldwide and a leading cause of cancer-related mortality,posing a persistent challenge to global public health1.In recent decades,the landscape of breast cancer care has been profoundly reshaped by the rapid development of precision medicine,targeted therapy,immunotherapy,and clinical translational research.
文摘Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance patients remains limited.This study examined real-world outcomes of palbociclib plus endocrine therapy in Asian patients,with additional subgroup analyses by age and performance status.Methods:We retrospectively analyzed 46 consecutive Asian patients with recurrent or de novo HR+/HER2−breast cancer treated with first-line palbociclib plus ET between April 2021 and March 2025.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall response rate(ORR),disease control rate(DCR),and safety.Subgroup analyses were performed by age(<70 vs.≥70 years)and performance status(PS;0–1 vs.2–3).Results:The median PFS was 26.6 months(range,1.4–69.5).Stratified by age,median PFS was 26.9 months in patients<70 years and 26.2 months in those≥70 years(p=0.760).By PS,PFS was 26.9 months for PS 0–1 and 17.8 months for PS 2–3(p=0.099).ORR was 60.9%and DCR 93.5%;notably,all PS 2–3 patients achieved disease control.Hematologic toxicities were common,with neutropenia(80.4%)and leukopenia(86.7%)predominating,but grade≥3 anemia was rare(2.2%).Elderly patients experienced anemia more frequently,while overall toxicity remained manageable.Dose reductions occurred in 47.8%without loss of efficacy.Conclusions:In routine Japanese practice,palbociclib plus ET provided prolonged PFS and high disease control consistent with pivotal trials and international real-world evidence.Importantly,elderly patients tolerated treatment well,and selected PS 2–3 patients also derived clinical benefit.These findings indicate that neither age nor PS alone should preclude the use of palbociclib in carefully monitored real-world patients.
文摘Objective:To investigate the long-term prognosis and postoperative cosmetic outcomes of breast-conserving surgery combined with sentinel lymph node biopsy in patients with early-stage breast cancer,providing a reference for the selection of clinical treatment plans.Methods:A retrospective analysis was conducted on the clinical data of 68 patients with early-stage breast cancer admitted from January 2022 to December 2025.Based on the surgical approach,patients were divided into an observation group(breast-conserving surgery+sentinel lymph node biopsy)and a control group(other surgical methods such as modified radical mastectomy/total mastectomy).Clinical and pathological characteristics,incidence of postoperative complications,follow-up prognosis,and satisfaction with cosmetic outcomes were compared between the two groups.Results:Among the 68 patients,41 were in the observation group and 27 in the control group.The average age of patients in the observation group was(54.32±8.15)years,while that in the control group was(62.45±9.76)years.The average tumor size in the observation group was(1.86±0.72)cm,compared to(3.21±1.45)cm in the control group.The incidence of postoperative complications in the observation group was 9.76%,significantly lower than that in the control group at 33.33%(P<0.05).The 6-month disease-free survival rate was 95.12%in the observation group and 88.89%in the control group,with no statistically significant difference between the two groups(P>0.05).The excellent and good rate of cosmetic outcomes in the observation group was 87.80%,significantly higher than that in the control group at 29.63%(P<0.05).Conclusion:Breast-conserving surgery combined with sentinel lymph node biopsy for early-stage breast cancer can achieve long-term prognostic outcomes comparable to those of traditional radical surgery,with the advantages of fewer postoperative complications and superior cosmetic results.This approach is worthy of clinical promotion and application,particularly for early-stage breast cancer patients who have a demand for preserving breast morphology.
文摘BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.
基金supported by National Research Foundation(NRF)of Korea grants funded by the Korean government,the Ministry of Science and ICT[NRF-2022R1A2C1006737 to Joo-Won Park,NRF-2022R1I1A1A0106408112 to Min Hee Kim].
文摘Breast cancer is one of the most prevalent malignancies among women and comprises a heterogeneous spectrum of molecular subtypes with distinct biological behaviors.Among various regulatory molecules,sphingolipids play pivotal roles in dynamically modulating fundamental cellular processes such as proliferation,apoptosis,and metastasis through metabolic interconversions,including phosphorylation,glycosylation,and the generation of sphingosine-1-phosphate.This review aims to elucidate the mechanisms through which sphingolipid metabolism orchestrates cancer cell fate and drives breast cancer progression.Particular emphasis is placed on the balance between proapoptotic ceramides and pro-survival metabolites,such as sphingosine-1-phosphate,which collectively influence tumor growth and the therapeutic response.Additional sphingolipid species,including glucosylceramide and gangliosides(GD2,GD3,GM1,and GM3),have also been implicated in promoting breast cancer development.Furthermore,sphingolipid-based therapeutic strategies,including immunotherapy and antibody therapy,are discussed.By providing a comprehensive overview of sphingolipid metabolism,this review aims to identify novel therapeutic targets that may help overcome treatment resistance and improve clinical outcomes in breast cancer.
基金supported by the National Natural Science Foundation of China(Grant No.:82560497,82260502,82272656)Guizhou Provincial Basic Research Program(Grant No.:Natural Science,MS[2025]-495)Talent Fund of Guizhou Provincial People’s Hospital(Grant No.:2022-33).
文摘Background:As a heterogeneous disease,breast cancer requires refined classification frameworks that can effectively guide targeted therapies.However,traditional methods fail to capture the comprehensive molecular insights needed for this purpose.Methods:To comprehensively capture breast cancer heterogeneity,we employed integrative clustering that incorporates six molecular features from 670 breast cancer samples.Ten distinct clustering algorithms were combined to ensure robust subtype identification,and the identified subtypes were validated in four independent datasets.Subsequently,we constructed a survival support vector machine prognostic model based on key molecular features to enhance survival prediction and clinical applicability.Results:Five novel subtypes were identified:consensus subtypes 1–5(CS1–CS5).CS2 was an aggressive subtype with elevated TP53 mutation rates,high tumor mutational burden,and strong sensitivity to YM-155 and ispinesib.Conversely,CS5 exhibited stable genomics with enhanced nucleotide excision repair and favorable prognoses.CS2 and CS4 showed enriched immune checkpoint expression,indicating potential immunotherapy responsiveness,while CS1 and CS5 exhibited immune-cold profiles.The survival support vector machine model effectively predicted survival outcomes across independent datasets.Conclusions:The refined breast cancer classification framework developed in this research uncovers new insights into molecular heterogeneity,enhances risk stratification,and enables the identification of promising therapeutic targets.The potential of this framework to optimize personalized treatment strategies warrants further clinical validation.
基金supported by the National Natural Science Foundation of China(Grant No.82404074)the Science and Technology Major Project(Grant No.2024ZD0519805).
文摘Breast cancer is the most common malignant tumor among women globally and poses a major public health challenge due to limitations in traditional diagnostic and treatment processes,such as subjective interpretation biases and inefficient multidimensional data integration.Artificial intelligence(AI),particularly deep learning and machine learning technologies,has emerged as a transformative tool in addressing these issues.Clinically,AI has been widely applied in imaging screening to improve detection rates and reduce reading time,digital pathology for precise tumor typing and gene mutation prediction,treatment decisionsupport systems to enhance guideline compliance,and drug research and development to accelerate target identification and virtual screening.Despite these achievements,AI implementation faces challenges,such as data standardization issues,limited model generalization,low clinical accessibility,and unclear ethical-legal responsibilities,which require targeted solutions that include national data standards,multi-center training,hierarchical physician training,and explainable AI.Future directions involve multimodal data integration,human-AI collaborative multidisciplinary team models,and extension to full-cycle health management from prevention-to-rehabilitation.This review provides a systematic overview of the role of AI in breast cancer care,offering insights for clinical practice and scientific research innovation,and supporting the transition toward personalized and intelligent medicine in oncology.
基金funded by the Deutsche Forschungsgemeinschaft(DFG)grant number(KA2663/3-1)supported by the Ministry of Science,Research and Cultural Affairs of the State of Brandenburg.
文摘Objectives:Vascular endothelial growth factor(VEGF)regulates tumor vascularization in response to hypoxia and inflammatory signals.The polyphenol curcumin is supposed to interfere with inflammation-induced VEGF secretion and might therefore support anti-VEGF-based treatments.We aimed to investigate the interaction between curcumin and the inflammatory cytokine Interleukin-1β(IL-1β)for VEGF secretion in breast cancer cell lines representing major breast cancer subtypes.Methods:VEGF in cell cultures was detected by Western blot and enzyme-linked immunosorbent assay(ELISA).Kinase phosphorylation was investigated by Western blotting.Gene expressions were analyzed by correlation tests.VEGF was evaluated in a retrospective breast cancer cohort by immunohistochemistry.Survival analysis was performed by the Kaplan-Meier algorithm.Results:VEGF secretion and kinase signaling in response to IL-1βand curcumin varied significantly for the cell lines MCF-7(Luminal A),SK-BR-3(HER2/neu+),MDA-MB-231,and UACC-3199(triple negative breast cancer).All cell lines increased VEGF secretion under hypoxia,but IL-1βincreased VEGF secretion only in MCF-7 cells.Curcumin inhibited VEGF secretion in MDA-MB-231,but increased it in MCF-7 and UACC-3199 cells.Curcumin induced phosphorylation of extracellular signal-regulated kinase(ERK)and p38-mitogen-activated protein kinase(p38-MAPK).However,inhibitor experiments demonstrated that ERK was more important for VEGF secretion.In gene expression data from the METABRIC study,no clear correlation of hypoxia-induced factor(HIF1A),IL-1β,and VEGF mRNA expression was observed;however,a suggested crosstalk of hypoxia and inflammatory pathways was observed.Conclusion:These dissimilar responses of breast cancer cell lines suggest that therapy efficiency with anti-VEGF,anti-IL-1β,or curcumin will also vary within breast cancers.
文摘Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strategies imperative.Although elevated expression of discs large homolog 3(DLG3)has been reported in BRCA,its functional role in disease progression remains unclear.We performed bioinformatic analyses of clinical datasets to evaluate the prognostic significance of DLG3 expression in BRCA patients.In vitro gain-and loss-of-function experiments were conducted to assess the impact of DLG3 on BRCA cell proliferation,migration,and colony formation.Transcriptomic profiling,coupled with pharmacological inhibition,was employed to identify and validate downstream signaling pathways.Additionally,we extended our validation to an in vivo model to assess the role of DLG3 in tumor progression.We found that elevated DLG3 levels correlated with poor prognosis in breast cancer patients.Functionally,DLG3 overexpression significantly promoted cell proliferation and migration in estrogen receptor-positive MCF7 and triple-negative MDA-MB-231 breast cancer cells,whereas its knockdown suppressed these effects.Transcriptomic analyses revealed that DLG3 activates signal transducer and activator of transcription 3(STAT3)signaling,a finding further corroborated by Western blot.Critically,treatment with the STAT3 inhibitor Stattic attenuated DLG3-driven proliferation and migration,supporting a DLG3-STAT3 oncogenic axis.Furthermore,in vivo studies validated the role of DLG3 in promoting tumor growth and its correlation with elevated STAT3 signaling,consistent with our in vitro findings.Our findings establish DLG3 as a novel driver of breast cancer progression that directly activates STAT3 signaling.DLG3 thus represents both a potential prognostic biomarker and a promising therapeutic target for aggressive breast cancer subtypes,including triple-negative breast cancer.
基金supported by the Science and Technology Strategic Cooperation Programs of Luzhou Municipal People's Government and Southwest Medical University(No.2024LZXNYDJ017)the Project Program of the Science and Technology Department of Sichuan Province(No.2025zNSFSC0679)the Project Program of Chongqing Science and Technology Bureau(No.cstc2020jcyjmsxmX1037).
文摘Although the combination of chemotherapy and immunotherapy can improve the treatment of breast cancer,traditional drugs are highly toxic because they do not specifically target tumors.In this study,we developed a self-driving bacteria/nanoparticle biohybrid called Bif@PDA-aPD1/DOX-Lip by attaching polydopamine(PDA)coated doxorubicin(DOX)liposomes and the immune checkpoint inhibitor anti-programmed cell death protein 1 antibody(aPD-1)to Bifidobacterium infantis(B.infantis,Bif).Using the homing abilities of bacteria,Bif@PDA-aPD1/DOX-Lip could actively accumulate in tumor tissue,releasing DOX and aPD-1 in the acidic environment to have a synergistic anti-tumor effect.Results show that the concentration of DOX in tumors of the Bif@PDA-aPD1/DOX-Lip group was 6.31 times higher than in the free DOX group.The combination of DOX and aPD-1 not only killed tumor cells but also promoted immune normalization by maturing dendritic cells(DCs),increasing M1 macrophage ratio,and enhancing infiltration of CD8^(+) and CD4^(+)T cells in tumors and spleen.Therefore,Bif@PDA-aPD1/DOX-Lip therapy significantly inhibited tumor growth and increased the average survival time of mice to over 80 days.The Bif@PDA-aPD1/DOX-Lip biomotors offer a highly effective method for enhancing chemo-immunotherapy in solid tumors.
文摘Traditional artificial intelligence(AI)-based methods for breast cancer diagnosis often rely on a single modality,such as ultrasound images.With the rise of multimodal approaches,multiple data sources,including imaging from diverse medical modalities,structured clinical information,and unstructured medical reports,are increasingly integrated to provide richer and more informative signals for model training.This survey reviews the data modalities employed in AI-based breast cancer research,examines common multimodal combinations and fusion strategies,and discusses their applications across clinical tasks such as diagnosis,treatment planning,and outcome prediction.By consolidating current literature and identifying critical gaps,this survey aims to guide future research toward the development of reliable,clinically relevant multimodal AI systems for use in breast cancer management.
基金funded by Al Jalila Foundation-Research Grant(AJF2023-078)to SSMS.
文摘Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabolism,in the aggressiveness and metastatic behavior of BC.Methods:A comprehensive analysis was performed using in silico transcriptomic data(n=2509 patients),immunohistochemical profiling of BC tissues(n=103),and validation through western blotting in multiple BC cell lines.Gene expression and survival analyses were conducted using Tumor Immune Estimation Resource(TIMER),Gene Expression Profiling Interactive Analysis 2(GEPIA2),and the cBioPortal for cancer genomics(cBioPortal)platforms.Correlations between PNP and key epithelial–mesenchymal transition(EMT)markers,molecular subtypes,tumor grades,and stages were examined.Results:PNP was significantly overexpressed in human epidermal growth factor receptor 2(HER-2)-positive and triple-negative BCs compared to luminal subtypes.High PNP levels were strongly associated with advanced BC stages,high-grade tumors,EMT phenotypes,and poor overall survival.Notably,HER-2 inhibition suppressed PNP expression,while PNP gene silencing induced HER-2 upregulation,revealing a reciprocal regulatory loop.Dual inhibition of PNP and HER-2 resulted in a significant reduction in cell viability compared to HER-2 inhibition alone.Conclusion:Collectively,PNP emerges as a promising biomarker of BC aggressiveness and progression.Its reciprocal interaction with HER-2 underscores its potential as a therapeutic target.Dual targeting of PNP and HER-2 may offer a novel strategy for improving outcomes in aggressive BC subtypes.
基金supported by the Natural Science Foundation of Jilin Province(No.SKL202302002).
文摘Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis.Herein,the targeted theranostic platform of cysteine-modified gold nanodots-sulfhydrated luteinizing hormone releasing hormone(CGN-SLR)nanosystem was designed for target recognition and precise dual-mode imaging-guided photothermal therapy(PTT)against TNBC.On the one hand,the CGN-SLR nanosystem can serve as an ideal targeting fluorescent probe and computed tomography(CT)enhancer to facilitate the accurate diagnosis and surgical guidance of TNBC.On the other hand,the CGN-SLR nanosystem with great targeting and PTT ability can significantly inhibit the growth of TNBC,without causing harm to normal tissues and healthy organs.It provides an effective strategy for the diagnosis and treatment of TNBC through the rational design of multifunctional nanoplatform with target recognition,multiple imaging guidance/monitoring,and high-efficiency PTT.
基金supported by grants from National Science and Technology Major Project(Grant No.2025ZD0544000)National Natural Science Foundation of China(Grant No.82171898)+2 种基金Deng Feng Project of High-level Hospital Construction(Grant No.DFJHBF202109)Beijing Science and Technology Innovation Medical Development Foundation(Grant No.KC2023-JX-0270-09)Development Center for Medical Science&Technology National Health commission of the People’s Republic of China(Grant No.WKZX2025RL0130)。
文摘Breast cancer exhibits profound biological and spatial heterogeneity,which contributes to variable responses to neoadjuvant chemotherapy(NAC)and challenges precision treatment planning.Radiomics,an emerging discipline that converts standard medical images into high-dimensional quantitative data,offers a non-invasive and reproducible means to capture tumor phenotype,heterogeneity,and treatment-induced changes.This review provides a comprehensive overview of recent advances in radiomics for breast cancer NAC,emphasizing the roles in predicting a pathologic complete response(pCR),monitoring early therapeutic efficacy,and quantifying intratumoral heterogeneity.Among imaging modalities,magnetic resonance imaging(MRI)-based radiomics,particularly utilizing dynamic contrast-enhanced and diffusion-weighted sequences,demonstrates robust predictive performance for the pCR,with multi-center studies reporting area under the curve(AUC)values>0.80.Longitudinal and delta-radiomics approaches further enhance early response evaluation by tracking temporal alterations in imaging features that precede measurable morphologic regression.Radiomic assessment of tumor heterogeneity,especially in triple-negative breast cancer(TNBC),reveals strong associations with immune infiltration,metabolic reprogramming,and therapeutic resistance,providing mechanistic insight into radiomic biomarkers.Integrative multi-omics frameworks,combining radiomics with genomics,transcriptomics and pathomics,are increasingly elucidating the biological underpinnings of imaging phenotypes,improving both model interpretability and clinical relevance.Despite these advances,widespread clinical adoption of radiomics is limited by methodologic variability,lack of standardization,and insufficient external validation.Future efforts should focus on harmonized imaging protocols,explainable artificial intelligence,and prospective multi-center trials to translate radiomics into a clinically actionable tool.Collectively,radiomics represents a transformative approach for individualized response prediction and dynamic treatment optimization in precision breast cancer management(Figure 1).
