BACKGROUND Breast hamartomas are rare benign breast tumors,with an incidence rate of 0.8%-4.8%.Further,the coexistence of hamartomas and carcinoma is also uncommon.Our case report presents a unique instance where inva...BACKGROUND Breast hamartomas are rare benign breast tumors,with an incidence rate of 0.8%-4.8%.Further,the coexistence of hamartomas and carcinoma is also uncommon.Our case report presents a unique instance where invasive ductal carcinoma(IDC)and ductal carcinoma in situ were found both inside and outside a breast hamartoma.This is the second case reported in the literature.CASE SUMMARY A 51-year-old woman presented with a 6.0 cm breast tumor on mammography and ultrasound,with suspicious areas indicative of malignant transformation.Biopsy of the suspicious area confirmed IDC with intraductal carcinoma.Breast magnetic resonance imaging showed typical hamartoma changes with irregular areas of abnormal enhancement both inside and outside.A breast-conserving surgery was performed,and postoperative pathology confirmed mammary hamartoma,concurrent with IDC and intraductal carcinoma occurring both inside and outside the hamartoma.Subsequently,appropriate adjuvant therapy was initiated.Currently,the patient is in good condition.Breast cancer may be located both inside and outside the ipsilateral mammary hamartoma,which is difficult to detect preoperatively,especially when there is a focus of intraductal carcinoma,requiring accurate assessment of the tumor extent by modern imaging techniques.Early detection of the coexistence of cancer is clinically important as it can alter patient management.CONCLUSION This case emphasizes the importance of modern imaging techniques in accurately evaluating mammary hamartomas associated with malignancies prior to surgery.展开更多
Background: Conventional radiation therapy is a technique that uses ionizing radiation to destroy tumor cells. Along with surgery, chemotherapy, hormonotherapy and target therapy, it plays a crucial role in the manage...Background: Conventional radiation therapy is a technique that uses ionizing radiation to destroy tumor cells. Along with surgery, chemotherapy, hormonotherapy and target therapy, it plays a crucial role in the management of breast cancer by reducing its overall mortality and recurrences. Methods: We conducted a retrospective and descriptive study by using the records of patients treated in the radiotherapy department of the Douala General Hospital from January 2015 to December 2019. Data concerning radiation-induced toxicities were collected using a pre-established and pre-tested survey and transferred to the CTCAE Version 4.0 software. Data analysis was performed using SPSS version 20.0. Results: A total of 206 records were selected. The average age was 46.7 ± 8.2 years. The most represented histological type was invasive ductal carcinoma (n = 187, 90.7%). Multimodality treatment was used in every patient in our series with chemotherapy, surgery, and adjuvant radiation therapy (n = 88, 42.7%) been the most represented. More than half of the participants (n = 108, 52.4%) received a total dose >50 grays, only 89 (43.2%) received the classical fractionation of 2 grays/cession, and the average duration of radiation therapy was 36.8 ± 15.4 days. We encountered 155 (75.2%) side effects. There were more acute toxicities than late toxicities, at 115 (74.1%) versus 40 (25.8%). The main acute lesions were radiodermatitis (68.6%), breast pain (16.5%), radiation pneumonitis (12.2%), and acute pericarditis (2.6%). As late lesions, we identified radiodermatitis (52.5%), radiation pneumonitis (32.5%), and lymphoedema (15%). A total dose >50 grays [p 0.001, OR: 2.7 (1.58 - 4.9)], and conservative surgery [p = 0.04, OR: 2.3 (1.3 - 4.1)], seemed to increase the occurrence of early side effects on bivariate analysis. However, after multivariate logistic regression, only a total dose >50 grays [p = 0.005, OR: 2.1 (1.1 - 6.7)] remained a predictive factor associated to early side effects. We found no factors related to late side effect occurrences. Conclusion: The frequency of side effects of radiation therapy for breast cancer at the Douala General Hospital remains relatively high. Both early and late lesions remained present with early toxicities been the most common. Meticulous strategies along with an enhancement of both human and materials resources are paramount in order to reduce their frequency and morbidity.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
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
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
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 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
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
Accurate segmentation of breast cancer in mammogram images plays a critical role in early diagnosis and treatment planning.As research in this domain continues to expand,various segmentation techniques have been propo...Accurate segmentation of breast cancer in mammogram images plays a critical role in early diagnosis and treatment planning.As research in this domain continues to expand,various segmentation techniques have been proposed across classical image processing,machine learning(ML),deep learning(DL),and hybrid/ensemble models.This study conducts a systematic literature review using the PRISMA methodology,analyzing 57 selected articles to explore how these methods have evolved and been applied.The review highlights the strengths and limitations of each approach,identifies commonly used public datasets,and observes emerging trends in model integration and clinical relevance.By synthesizing current findings,this work provides a structured overview of segmentation strategies and outlines key considerations for developing more adaptable and explainable tools for breast cancer detection.Overall,our synthesis suggests that classical and ML methods are suitable for limited labels and computing resources,while DL models are preferable when pixel-level annotations and resources are available,and hybrid pipelines are most appropriate when fine-grained clinical precision is required.展开更多
Oncology Research Editorial Office Published:19 January 2026 The published article titled“ABCB5-ZEB1 Axis Promotes Invasion and Metastasis in Breast Cancer Cells”has been retracted from Oncology Research,Vol.25,No.3...Oncology Research Editorial Office Published:19 January 2026 The published article titled“ABCB5-ZEB1 Axis Promotes Invasion and Metastasis in Breast Cancer Cells”has been retracted from Oncology Research,Vol.25,No.3,2017,pp.305-316.DOI:10.3727/096504016X14734149559061 URL:https://www.techscience.com/or/v25n3/56810.展开更多
Breast cancer screening programs rely heavily on mammography for early detection;however,diagnostic performance is strongly affected by inter-reader variability,breast density,and the limitations of conven-tional comp...Breast cancer screening programs rely heavily on mammography for early detection;however,diagnostic performance is strongly affected by inter-reader variability,breast density,and the limitations of conven-tional computer-aided detection systems.Recent advances in deep learning have enabled more robust and scalable solutions for large-scale screening,yet a systematic comparison of modern object detection architectures on nationally representative datasets remains limited.This study presents a comprehensive quantitative comparison of prominent deep learning–based object detection architectures for Artificial Intelligence-assisted mammography analysis using the MammosighTR dataset,developed within the Turkish National Breast Cancer Screening Program.The dataset comprises 12,740 patient cases collected between 2016 and 2022,annotated with BI-RADS categories,breast density levels,and lesion localization labels.A total of 31 models were evaluated,including One-Stage,Two-Stage,and Transformer-based architectures,under a unified experimental framework at both patient and breast levels.The results demonstrate that Two-Stage architectures consistently outperform One-Stage models,achieving approximately 2%–4%higher Macro F1-Scores and more balanced precision–recall trade-offs,with Double-Head R-CNN and Dynamic R-CNN yielding the highest overall performance(Macro F1≈0.84–0.86).This advantage is primarily attributed to the region proposal mechanism and improved class balance inherent to Two-Stage designs.One-Stage detectors exhibited higher sensitivity and faster inference,reaching Recall values above 0.88,but experienced minor reductions in Precision and overall accuracy(≈1%–2%)compared with Two-Stage models.Among Transformer-based architectures,Deformable DEtection TRansformer demonstrated strong robustness and consistency across datasets,achieving Macro F1-Scores comparable to CNN-based detectors(≈0.83–0.85)while exhibiting minimal performance degradation under distributional shifts.Breast density–based analysis revealed increased misclassification rates in medium-density categories(types B and C),whereas Transformer-based architectures maintained more stable performance in high-density type D tissue.These findings quantitatively confirm that both architectural design and tissue characteristics play a decisive role in diagnostic accuracy.Overall,the study provides a reproducible benchmark and highlights the potential of hybrid approaches that combine the accuracy of Two-Stage detectors with the contextual modeling capability of Transformer architectures for clinically reliable breast cancer screening systems.展开更多
Objective Tumor-associated macrophages(TAMs)contribute to chemoresistance in triple-negative breast cancer(TNBC),yet strategies to reprogram TAMs while enhancing chemotherapy efficacy remain limited.This study investi...Objective Tumor-associated macrophages(TAMs)contribute to chemoresistance in triple-negative breast cancer(TNBC),yet strategies to reprogram TAMs while enhancing chemotherapy efficacy remain limited.This study investigated whether Viscum album L.var.coloratum agglutinin(VCA)could sensitize TNBC cells to doxorubicin(DOX)and modulate TAM-mediated chemoresistance in three-dimensional(3D)co-culture models.Methods MDA-MB-231 TNBC cells were co-cultured with RAW264.7 macrophages in collagen-embedded 3D spheroids.Spheroid viability was assessed using an ATP-based luminescent assay.Cytokine secretion and epithelial-mesenchymal transition(EMT)markers were measured using ELISA and Western blotting.Drug synergy was evaluated using combination index(CI)calculations.Results VCA-DOX combination demonstrated synergistic cytotoxicity exclusively in co-culture spheroids(CI=0.72),reducing viability to 25.9%(p<0.001),while showing no synergy in monoculture(CI=1.52).Combination treatment decreased VEGF secretion by 49%and IL-6 by 74%,while elevating TNF-α2.7-fold,suggesting macrophage reprogramming.VCA enhanced E-cadherin expression while suppressing mesenchymal markers in co-culture spheroids and reduced Matrigel invasion by 60%(p<0.001).Conclusion VCA-DOX combination demonstrates synergistic anticancer effects through TAM reprogramming and enhanced chemosensitization specifically in 3D co-culture models,warranting further investigation for overcoming macrophage-mediated chemoresistance in TNBC.展开更多
Objectives:Progesterone(P4)is believed to inhibit breast cancer growth,but its role in counteracting estrogen(E2)-driven progression remains unclear.This study aimed to investigate the inhibitory effect of P4 on E2-in...Objectives:Progesterone(P4)is believed to inhibit breast cancer growth,but its role in counteracting estrogen(E2)-driven progression remains unclear.This study aimed to investigate the inhibitory effect of P4 on E2-induced cell proliferation,migration,and invasion in Estrogen receptor(ER)+/progesterone receptor(PR)+breast cancer cells by examining its regulatory role in the epithelial-mesenchymal transition(EMT).Methods:ER and PRpositive MCF-7 clonal variant(MCF-7 CV)breast cancer cells were treated with E2 and co-treated with various concentrations of P4.The effects on cell proliferation,migration,and invasion were assessed.The expression of key EMT markers(E-cadherin,N-cadherin,vimentin),transcription factors(Snail,Slug),and apoptosis-related genes(p53,B-cell lymphoma 2[BCL-2],BCL2-associated X[BAX])were analyzed.Results:P4 significantly inhibited E2-induced cell proliferation in a dose-dependent manner.In the presence of E2,P4 treatment reversed EMT characteristics by increasing E-cadherin while decreasing N-cadherin,vimentin,Snail,and Slug.Consequently,P4 inhibited E2-stimulated cell migration and invasion.Furthermore,P4 treatment promoted apoptosis by upregulating BAX and p53 and downregulating BCL-2.Conclusion:Progesterone can counteract estrogen-driven breast cancer progression in ER+/PR+cells by inhibiting proliferation,reversing the EMT process,and inducing apoptosis.These findings provide mechanistic insight into the protective role of PR signaling in breast cancer.展开更多
基金Supported by Jilin City Science and Technology Innovation Development Plan Project,China,No.20230406201Jilin Province Traditional Chinese Medicine Technology Project,China,No.2024159.
文摘BACKGROUND Breast hamartomas are rare benign breast tumors,with an incidence rate of 0.8%-4.8%.Further,the coexistence of hamartomas and carcinoma is also uncommon.Our case report presents a unique instance where invasive ductal carcinoma(IDC)and ductal carcinoma in situ were found both inside and outside a breast hamartoma.This is the second case reported in the literature.CASE SUMMARY A 51-year-old woman presented with a 6.0 cm breast tumor on mammography and ultrasound,with suspicious areas indicative of malignant transformation.Biopsy of the suspicious area confirmed IDC with intraductal carcinoma.Breast magnetic resonance imaging showed typical hamartoma changes with irregular areas of abnormal enhancement both inside and outside.A breast-conserving surgery was performed,and postoperative pathology confirmed mammary hamartoma,concurrent with IDC and intraductal carcinoma occurring both inside and outside the hamartoma.Subsequently,appropriate adjuvant therapy was initiated.Currently,the patient is in good condition.Breast cancer may be located both inside and outside the ipsilateral mammary hamartoma,which is difficult to detect preoperatively,especially when there is a focus of intraductal carcinoma,requiring accurate assessment of the tumor extent by modern imaging techniques.Early detection of the coexistence of cancer is clinically important as it can alter patient management.CONCLUSION This case emphasizes the importance of modern imaging techniques in accurately evaluating mammary hamartomas associated with malignancies prior to surgery.
文摘Background: Conventional radiation therapy is a technique that uses ionizing radiation to destroy tumor cells. Along with surgery, chemotherapy, hormonotherapy and target therapy, it plays a crucial role in the management of breast cancer by reducing its overall mortality and recurrences. Methods: We conducted a retrospective and descriptive study by using the records of patients treated in the radiotherapy department of the Douala General Hospital from January 2015 to December 2019. Data concerning radiation-induced toxicities were collected using a pre-established and pre-tested survey and transferred to the CTCAE Version 4.0 software. Data analysis was performed using SPSS version 20.0. Results: A total of 206 records were selected. The average age was 46.7 ± 8.2 years. The most represented histological type was invasive ductal carcinoma (n = 187, 90.7%). Multimodality treatment was used in every patient in our series with chemotherapy, surgery, and adjuvant radiation therapy (n = 88, 42.7%) been the most represented. More than half of the participants (n = 108, 52.4%) received a total dose >50 grays, only 89 (43.2%) received the classical fractionation of 2 grays/cession, and the average duration of radiation therapy was 36.8 ± 15.4 days. We encountered 155 (75.2%) side effects. There were more acute toxicities than late toxicities, at 115 (74.1%) versus 40 (25.8%). The main acute lesions were radiodermatitis (68.6%), breast pain (16.5%), radiation pneumonitis (12.2%), and acute pericarditis (2.6%). As late lesions, we identified radiodermatitis (52.5%), radiation pneumonitis (32.5%), and lymphoedema (15%). A total dose >50 grays [p 0.001, OR: 2.7 (1.58 - 4.9)], and conservative surgery [p = 0.04, OR: 2.3 (1.3 - 4.1)], seemed to increase the occurrence of early side effects on bivariate analysis. However, after multivariate logistic regression, only a total dose >50 grays [p = 0.005, OR: 2.1 (1.1 - 6.7)] remained a predictive factor associated to early side effects. We found no factors related to late side effect occurrences. Conclusion: The frequency of side effects of radiation therapy for breast cancer at the Douala General Hospital remains relatively high. Both early and late lesions remained present with early toxicities been the most common. Meticulous strategies along with an enhancement of both human and materials resources are paramount in order to reduce their frequency and morbidity.
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 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.
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 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).
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funded by BK21 FOUR(Fostering Outstanding Universities for Research)(No.:5199990914048).
文摘Accurate segmentation of breast cancer in mammogram images plays a critical role in early diagnosis and treatment planning.As research in this domain continues to expand,various segmentation techniques have been proposed across classical image processing,machine learning(ML),deep learning(DL),and hybrid/ensemble models.This study conducts a systematic literature review using the PRISMA methodology,analyzing 57 selected articles to explore how these methods have evolved and been applied.The review highlights the strengths and limitations of each approach,identifies commonly used public datasets,and observes emerging trends in model integration and clinical relevance.By synthesizing current findings,this work provides a structured overview of segmentation strategies and outlines key considerations for developing more adaptable and explainable tools for breast cancer detection.Overall,our synthesis suggests that classical and ML methods are suitable for limited labels and computing resources,while DL models are preferable when pixel-level annotations and resources are available,and hybrid pipelines are most appropriate when fine-grained clinical precision is required.
文摘Oncology Research Editorial Office Published:19 January 2026 The published article titled“ABCB5-ZEB1 Axis Promotes Invasion and Metastasis in Breast Cancer Cells”has been retracted from Oncology Research,Vol.25,No.3,2017,pp.305-316.DOI:10.3727/096504016X14734149559061 URL:https://www.techscience.com/or/v25n3/56810.
文摘Breast cancer screening programs rely heavily on mammography for early detection;however,diagnostic performance is strongly affected by inter-reader variability,breast density,and the limitations of conven-tional computer-aided detection systems.Recent advances in deep learning have enabled more robust and scalable solutions for large-scale screening,yet a systematic comparison of modern object detection architectures on nationally representative datasets remains limited.This study presents a comprehensive quantitative comparison of prominent deep learning–based object detection architectures for Artificial Intelligence-assisted mammography analysis using the MammosighTR dataset,developed within the Turkish National Breast Cancer Screening Program.The dataset comprises 12,740 patient cases collected between 2016 and 2022,annotated with BI-RADS categories,breast density levels,and lesion localization labels.A total of 31 models were evaluated,including One-Stage,Two-Stage,and Transformer-based architectures,under a unified experimental framework at both patient and breast levels.The results demonstrate that Two-Stage architectures consistently outperform One-Stage models,achieving approximately 2%–4%higher Macro F1-Scores and more balanced precision–recall trade-offs,with Double-Head R-CNN and Dynamic R-CNN yielding the highest overall performance(Macro F1≈0.84–0.86).This advantage is primarily attributed to the region proposal mechanism and improved class balance inherent to Two-Stage designs.One-Stage detectors exhibited higher sensitivity and faster inference,reaching Recall values above 0.88,but experienced minor reductions in Precision and overall accuracy(≈1%–2%)compared with Two-Stage models.Among Transformer-based architectures,Deformable DEtection TRansformer demonstrated strong robustness and consistency across datasets,achieving Macro F1-Scores comparable to CNN-based detectors(≈0.83–0.85)while exhibiting minimal performance degradation under distributional shifts.Breast density–based analysis revealed increased misclassification rates in medium-density categories(types B and C),whereas Transformer-based architectures maintained more stable performance in high-density type D tissue.These findings quantitatively confirm that both architectural design and tissue characteristics play a decisive role in diagnostic accuracy.Overall,the study provides a reproducible benchmark and highlights the potential of hybrid approaches that combine the accuracy of Two-Stage detectors with the contextual modeling capability of Transformer architectures for clinically reliable breast cancer screening systems.
基金supported by the Regional Innovation System&Education(RISE)program through the Jeollanamdo RISE center,funded by the Ministry of Education(MOE)and the Jeollanamdo,Republic of Korea(2025-RISE-14-003).
文摘Objective Tumor-associated macrophages(TAMs)contribute to chemoresistance in triple-negative breast cancer(TNBC),yet strategies to reprogram TAMs while enhancing chemotherapy efficacy remain limited.This study investigated whether Viscum album L.var.coloratum agglutinin(VCA)could sensitize TNBC cells to doxorubicin(DOX)and modulate TAM-mediated chemoresistance in three-dimensional(3D)co-culture models.Methods MDA-MB-231 TNBC cells were co-cultured with RAW264.7 macrophages in collagen-embedded 3D spheroids.Spheroid viability was assessed using an ATP-based luminescent assay.Cytokine secretion and epithelial-mesenchymal transition(EMT)markers were measured using ELISA and Western blotting.Drug synergy was evaluated using combination index(CI)calculations.Results VCA-DOX combination demonstrated synergistic cytotoxicity exclusively in co-culture spheroids(CI=0.72),reducing viability to 25.9%(p<0.001),while showing no synergy in monoculture(CI=1.52).Combination treatment decreased VEGF secretion by 49%and IL-6 by 74%,while elevating TNF-α2.7-fold,suggesting macrophage reprogramming.VCA enhanced E-cadherin expression while suppressing mesenchymal markers in co-culture spheroids and reduced Matrigel invasion by 60%(p<0.001).Conclusion VCA-DOX combination demonstrates synergistic anticancer effects through TAM reprogramming and enhanced chemosensitization specifically in 3D co-culture models,warranting further investigation for overcoming macrophage-mediated chemoresistance in TNBC.
基金supported by the Regional Innovation System&Education(RISE)program through the(Chungbuk Regional Innovation System&Education Center),funded by the Ministry of Education(MOE)and the(Chungcheongbuk-do),Republic of Korea(2025-RISE-11-014-03)In addition,this work was also supported by the Sejong Fellowship through the NRF funded by the Ministry of Science and ICT(RS-2025-00557567)to HKL.
文摘Objectives:Progesterone(P4)is believed to inhibit breast cancer growth,but its role in counteracting estrogen(E2)-driven progression remains unclear.This study aimed to investigate the inhibitory effect of P4 on E2-induced cell proliferation,migration,and invasion in Estrogen receptor(ER)+/progesterone receptor(PR)+breast cancer cells by examining its regulatory role in the epithelial-mesenchymal transition(EMT).Methods:ER and PRpositive MCF-7 clonal variant(MCF-7 CV)breast cancer cells were treated with E2 and co-treated with various concentrations of P4.The effects on cell proliferation,migration,and invasion were assessed.The expression of key EMT markers(E-cadherin,N-cadherin,vimentin),transcription factors(Snail,Slug),and apoptosis-related genes(p53,B-cell lymphoma 2[BCL-2],BCL2-associated X[BAX])were analyzed.Results:P4 significantly inhibited E2-induced cell proliferation in a dose-dependent manner.In the presence of E2,P4 treatment reversed EMT characteristics by increasing E-cadherin while decreasing N-cadherin,vimentin,Snail,and Slug.Consequently,P4 inhibited E2-stimulated cell migration and invasion.Furthermore,P4 treatment promoted apoptosis by upregulating BAX and p53 and downregulating BCL-2.Conclusion:Progesterone can counteract estrogen-driven breast cancer progression in ER+/PR+cells by inhibiting proliferation,reversing the EMT process,and inducing apoptosis.These findings provide mechanistic insight into the protective role of PR signaling in breast cancer.
