Stability and variability of molecular subtypes:comparative analysis of primary and metastatic triple-negative breast cancer

Objective:Triple-negative breast cancer(TNBC)is a heterogeneous and aggressive cancer.Although our previous study classified primary TNBC into four subtypes,comprehensive longitudinal investigations are lacking.Methods:We assembled a large-scale,real-world cohort comprised of 880 TNBC patients[465 early-stage TNBC(eTNBC)and 415 metastatic TNBC(mTNBC)patients]who were treated at Fudan University Shanghai Cancer Center.The longitudinal dynamics of TNBC subtypes during disease progression were elucidated in this patient cohort.Comprehensive analysis was performed to compare primary and metastatic lesions within specific TNBC subtypes.Results:The recurrence and metastasis rates within 3 years after initial diagnosis in the eTNBC cohort were 10.1%(47/465).The median overall survival(OS)in the mTNBC cohort was 27.2 months[95%confidence interval(CI),24.4–30.2 months],which indicated a poor prognosis.The prognostic significance of the original molecular subtypes in both eTNBC and mTNBC patients was confirmed.Consistent molecular subtypes were maintained in 77.5%of the patients throughout disease progression with the mesenchymal-like(MES)subtype demonstrating a tendency for subtype transition and brain metastasis.Additionally,a precision treatment strategy based on the metastatic MES subtype of target lesions resulted in improved progression-free survival in the FUTURE trial.Conclusions:Our longitudinal study comprehensively revealed the clinical characteristics and survival of patients with the original TNBC subtypes and validated the consistency of most molecular subtypes throughout disease progression.However,we emphasize the major importance of repeat pathologic confirmation of the MES subtype.

Effectiveness of a theory-based tailored mHealth physical activity intervention for women undergoing chemotherapy for breast cancer:A quasi-experimental study

Objectives:This study aimed to explore the effectiveness of the theory-based tailored mHealth physical activity(PA)intervention among patients with breast cancer undergoing chemotherapy.Methods:A quasi-experimental study design was adopted.A total of 60 breast cancer patients were selected from two tertiary hospitals in Shanghai and Hangzhou City from September 2019 to August 2021.According to the admission order,30 patients werefirst included in the control group,followed by 30 patients in the intervention group.A smartphone application(app)named“Breast Care”was developed based on social cognitive theory,self-efficacy theory,and the theory of planned behavior.The app integrated various functions,including information browsing,PA monitoring and feedback,symptom reporting,and social interaction.Patients in the intervention group received three months of personalized online PA guidance in addition to routine care.The control group received routine care.Baseline and post-intervention investigations after three months were conducted in two groups using the Short Form of International Physical Activity Questionnaire,the Hospital Anxiety and Depression Scale,and the Functional Assessment of Cancer TherapydBreast cancer.Results:After three months of intervention,compared to the control group,breast cancer patients in the intervention group showed significant improvements in walking,moderate PA,and overall PA(P<0.05).Compared to the baseline data,breast cancer patients in the intervention group had significant improvements in walking and overall PA after three months(P<0.05),whereas the control group experienced significant declines in walking,moderate PA,and overall PA after three months(P<0.05).There were statistically differences between the two groups in scores for anxiety,overall quality of life,and its dimensions,such as physical well-being,emotional well-being,and additional breast cancer well-being(P<0.05).Conclusions:The theory-based tailored mHealth PA intervention has demonstrated a positive impact on promoting PA behavior change and emotional management among breast cancer patients.The‘Breast Care’app integrated various practical behavior change strategies,offering valuable guidance for personalized remote rehabilitation support for cancer patients.

Correlation and predictive value of pathological complete response and ultrasound characteristic parameters in neoadjuvant chemotherapy for breast

BACKGROUND Breast cancer ranks as one of the most prevalent malignant tumors among women,significantly endangering their health and lives.While radical surgery has been a pivotal method for halting disease progression,it alone is insufficient for enhancing the quality of life for patients.AIM To investigate the correlation between ultrasound characteristic parameters of breast cancer lesions and clinical efficacy in patients undergoing neoadjuvant chemotherapy(NAC).METHODS Employing a case-control study design,this research involved 178 breast cancer patients treated with NAC at our hospital from July 2019 to June 2022.According to the Miller-Payne grading system,the pathological response,i.e.efficacy,of the NAC in the initial breast lesion after NAC was evaluated.Of these,59 patients achieved a pathological complete response(PCR),while 119 did not(non-PCR group).Ultrasound characteristics prior to NAC were compared between these groups,and the association of various factors with NAC efficacy was analyzed using univariate and multivariate approaches.RESULTS In the PCR group,the incidence of posterior echo attenuation,lesion diameter≥2.0 cm,and Alder blood flow grade≥II were significantly lower compared to the non-PCR group(P<0.05).The area under the curve values for predicting NAC efficacy using posterior echo attenuation,lesion diameter,and Alder grade were 0.604,0.603,and 0.583,respectively.Also,rates of pathological stage II,lymph node metastasis,vascular invasion,and positive Ki-67 expression were significantly lower in the PCR group(P<0.05).Logistic regression analysis identified posterior echo attenuation,lesion diameter≥2.0 cm,Alder blood flow grade≥II,pathological stage III,vascular invasion,and positive Ki-67 expression as independent predictors of poor response to NAC in breast cancer patients(P<0.05).CONCLUSION While ultrasound characteristics such as posterior echo attenuation,lesion diameter≥2.0 cm,and Alder blood flow grade≥II exhibit limited predictive value for NAC efficacy,they are significantly associated with poor response to NAC in breast cancer patients.

Evolving molecular subtyping of breast cancer advances precision treatment

Breast cancer is the second most prevalent cancer globally.In 2022,approximately 2.3 million newly diagnosed cases of female breast cancer occurred worldwide,and more than 665 thousand people lost their lives to this disease^(1).

Effect of resilience on quality of life and anxiety in patients with breast cancer

BACKGROUND The incidence of breast cancer is high,with serious implications in terms of lives and health.Relevant data show that there are approximately 1 million new cases of breast cancer reported annually,with a rising trend.Some patients have poor treatment effects and are prone to anxiety and other negative emotions,which affect their quality of life(QoL).AIM To explore the correlation between mental resilience,QoL,and anxiety in patients with breast cancer.METHODS Using convenience sampling,200 patients with breast cancer were selected from the First Affiliated Hospital of Hebei North University.These patients were investigated using the Conner-Davidson Resilience Scale,Self-Rating Anxiety Scale,and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire to analyze the impact of resilience in patients with breast cancer on their QoL and anxiety.RESULTS The mean(SD)mental resilience score of the patients with breast cancer was 59.68(±9.84)points,the anxiety score was 49.87(±8.26)points,and the QoL score was 59.73(±8.29)points.Overall,they showed low mental resilience,mild anxiety,and medium QoL.Anxiety was negatively correlated with mental resilience and QoL(r=-0.275,r=-0.289,P<0.05).QoL was positively correlated with mental resilience(r=0.513,P<0.05).Anxiety was a mediating variable between mental resilience and QoL,accounting for 8.58%of the mediating effect.CONCLUSION Regarding psychological elasticity,anxiety plays an intermediary role in QoL among patients with breast cancer.Medical staff can improve patients'mental resilience by reducing their anxiety and improving their QoL.

Personalized and continuous care intervention affects rehabilitation,living quality,and negative emotions of patients with breast cancer

BACKGROUND Breast cancer is among the most common malignancies worldwide.With progress in treatment methods and levels,the overall survival period has been prolonged,and the demand for quality care has increased.AIM To investigate the effect of individualized and continuous care intervention in patients with breast cancer.METHODS Two hundred patients with breast cancer who received systemic therapy at The First Affiliated Hospital of Hebei North University(January 2021 to July 2023)were retrospectively selected as research participants.Among them,134 received routine care intervention(routing group)and 66 received personalized and continuous care(intervention group).Self-rating anxiety scale(SAS),self-rating depression scale(SDS),and Functional Assessment of Cancer Therapy-Breast(FACT-B)scores,including limb shoulder joint activity,complication rate,and care satisfaction,were compared between both groups after care.RESULTS SAS and SDS scores were lower in the intervention group than in the routing group at one and three months after care.The total FACT-B scores and five dimensions in the intervention group were higher than those in the routing group at three months of care.The range of motion of shoulder anteflexion,posterior extension,abduction,internal rotation,and external rotation in the intervention group was higher than that in the routing group one month after care.The incidence of postoperative complications was 18.18%lower in the intervention group than in the routing group(34.33%;P<0.05).Satisfaction with care was 90.91% higher in the intervention group than in the routing group(78.36%;P<0.05).CONCLUSION Personalized and continuous care can alleviate negative emotions in patients with breast cancer,quicken rehabilitation of limb function,decrease the incidence of complications,and improve living quality and care satisfaction.

Polo-like kinase 1 as a biomarker predicts the prognosis and immunotherapy of breast invasive carcinoma patients

Invasive breast carcinoma(BRCA)is associated with poor prognosis and high risk of mortality.Therefore,it is critical to identify novel biomarkers for the prognostic assessment of BRCA.Methods:The expression data of polo-like kinase 1(PLK1)in BRCA and the corresponding clinical information were extracted from TCGA and GEO databases.PLK1 expression was validated in diverse breast cancer cell lines by quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting.Single sample gene set enrichment analysis(ssGSEA)was performed to evaluate immune infiltration in the BRCA microenvironment,and the random forest(RF)and support vector machine(SVM)algorithms were used to screen for the hub infiltrating cells and calculate the immunophenoscore(IPS).The RF algorithm and COX regression model were applied to calculate survival risk scores based on the PLK1 expression and immune cell infiltration.Finally,a prognostic nomogram was constructed with the risk score and pathological stage,and its clinical potential was evaluated by plotting calibration charts and DCA curves.The application of the nomogram was further validated in an immunotherapy cohort.Results:PLK1 expression was significantly higher in the tumor samples in TCGA-BRCA cohort.Furthermore,PLK1 expression level,age and stage were identified as independent prognostic factors of BRCA.While the IPS was unaffected by PLK1 expression,the TMB and MATH scores were higher in the PLK1-high group,and the TIDE scores were higher for the PLK1-low patients.We also identified 6 immune cell types with high infiltration,along with 11 immune cell types with low infiltration in the PLK1-high tumors.A risk score was devised using PLK1 expression and hub immune cells,which predicted the prognosis of BRCA patients.In addition,a nomogram was constructed based on the risk score and pathological staging,and showed good predictive performance.Conclusions:PLK1 expression and immune cell infiltration can predict post-immunotherapy prognosis of BRCA patients.

Assessing the Clinical Efficacy and Effectiveness of Sentinel Lymph Node Biopsy Combined with Breast-Conserving Surgery for Early-Stage Breast Cancer

Objective:To analyze the impact of sentinel lymph node biopsy(SLNB)combined with breast-conserving surgery in the clinical treatment of early-stage breast cancer.Methods:80 patients with early-stage breast cancer admitted to the Second Department of Breast Surgery at Dezhou Second People’s Hospital from September 2020 to September 2022 were selected and randomly divided into a control group and an observation group using the random number table method,with 40 cases in each group.The control group underwent a modified radical mastectomy,while the observation group underwent SLNB combined with breast-conserving surgery.The surgical efficacy and prognosis between the two groups were compared.Results:The observation group exhibited shorter operation,hospitalization,and extubation times,as well as less intraoperative blood loss and drainage volume,all of which were significantly better than those in the control group(P<0.05).Additionally,the observation group demonstrated a higher rate of excellent breast cosmetology and quality of life,with lower complication incidence,significantly outperforming the control group(P<0.05).There was no statistical difference in the metastasis rate and recurrence rate between the two groups(P>0.05).Conclusion:The combination of SLNB and breast-conserving surgery proves highly effective for patients with early-stage breast cancer,presenting fewer complications and enhancing both breast cosmetic outcomes and quality of life.

Understanding the mechanisms underlying obesity in remodeling the breast tumor immune microenvironment:from the perspective of inflammation

Obesity is a well-known modifiable risk factor for breast cancer and is considered a poor prognostic factor in pre-and post-menopausal women.While the systemic effects of obesity have been extensively studied,less is known about the mechanisms underlying obesityassociated cancer risk and the local consequences of obesity.Thus,obesity-induced inflammation has become the focus of research interest.Biologically,the development of cancer involves a complex interaction with numerous components.As the tumor immune microenvironment changes due to obesity-triggered inflammation,an increase in infiltration occurs for proinflammatory cytokines and adipokines,as well as adipocytes,immune cells,and tumor cells in the expanded adipose tissue.Complicated cellular-molecular crosstalk networks change critical pathways,mediate metabolic and immune function reprogramming,and have a significant role in tumor metastasis,proliferation,resistance,angiogenesis,and tumorigenesis.This review summarizes recent research findings on how inflammatory mediators in the in situ tumor microenvironment regulate the occurrence and development of breast cancer in the context of obesity.We analyzed the heterogeneity and potential mechanisms of the breast cancer immune microenvironment from the perspective of inflammation to provide a reference for the clinical transformation of precision targeted cancer therapy.

The role of AFAP1-AS1 in mitotic catastrophe and metastasis of triple-negative breast cancer cells by activating the PLK1 signaling pathway

Triple-negative breast cancer(TNBC)is characterized by fast growth,high metastasis,high invasion,and a lack of therapeutic targets.Mitosis and metastasis of TNBC cells are two important biological behaviors in TNBC malignant progression.It is well known that the long noncoding RNA AFAP1-AS1 plays a crucial role in various tumors,but whether AFAP1-AS1 is involved in the mitosis of TNBC cells remains unknown.In this study,we investigated the functional mechanism of AFAP1-AS1 in targeting Polo-like Kinase 1(PLK1)activation and participating in mitosis of TNBC cells.We detected the expression of AFAP1-AS1 in the TNBC patient cohort and primary cells by in situ hybridization(ISH),northern blot,fluorescent in situ hybridization(FISH)and cell nucleus/cytoplasm RNA fraction isolation.High AFAP1-AS1 expression was negatively correlated with overall survival(OS),disease-free survival(DFS),metastasis-free survival(MFS)and recurrence-free survival(RFS)in TNBC patients.We explored the function of AFAP1-AS1 by transwell,apoptosis,immunofluorescence(IF)and patient-derived xenograft(PDX)models in vitro and in vivo.We found that AFAP1-AS1 promoted TNBC primary cell survival by inhibiting mitotic catastrophe and increased TNBC primary cell growth,migration and invasion.Mechanistically,AFAP1-AS1 activated phosphorylation of the mitosis-associated kinase PLK1 protein.Elevated levels of AFAP1-AS1 in TNBC primary cells increased PLK1 pathway downstream gene expression,such as CDC25C,CDK1,BUB1 and TTK.More importantly,AFAP1-AS1 increased lung metastases in a mouse metastasis model.Taken together,AFAP1-AS1 functions as an oncogene that activates the PLK1 signaling pathway.AFAP1-AS1 could be used as a potential prognostic marker and therapeutic target for TNBC.

Next-generation antibody-drug conjugates revolutionize the precise classification and treatment of HER2-expressing breast cancer

The concept of antibody±drug conjugations(ADCs)can be tracked back to the early 20^(th) century when the renowned immunologist,Paul Ehrlich,proposed the idea of a"magic bullet",which utilizes ADCs for targeted destruction of microorganisms and tumor cells^(1).After nearly one century of development,ADCs have emerged as a rather promising approach in the treatment of cancer,especially breast cancer,which is the most common malignant tumor in women^(2).

Granular cell tumor of the breast:A case report and review of literature

BACKGROUND Granular cell tumor(GCT)of the breast(GCTB)is a rare neoplasm that can exhibit malignant characteristics both clinically and radiologically.This tumor can also coexist and colocalize with breast carcinoma.CASE SUMMARY We present a patient with this uncommon tumor and discuss the diagnostic and therapeutic approaches in order to further the knowledge of GCTB and prevent misdiagnosis and overtreatment.The characteristics of the tumor,methods of diagnosis,therapy and postoperative pathological outcomes were analyzed,and relevant literatures of GCTs were reviewed.The patient underwent surgery after core needle biopsy,and the excised neoplasm was sent for pathological examination.Histological analysis revealed nests of cells with abundant pink granular cytoplasm,confirming the diagnosis of GCTB.CONCLUSION As manifestations of GCT and malignancy can mimic each other,a careful histological examination is essential before major surgery.Treatment consisting of complete excision with close clinical follow-up is recommended.

Multi-center investigation of breast reconstruction after mastectomy from Chinese Society of Breast Surgery:A survey based on 31 tertiary hospitals(CSBrS-004)

Objective:Multi-center data on the current status and trends of breast reconstruction after mastectomy in China are lacking.Herein,we conducted a cross-sectional survey to investigate the current clinical practice pattern of postmastectomy breast reconstruction among Chinese female patients with breast cancer.Methods:A standardized questionnaire used to collect information on breast reconstruction among females diagnosed with breast cancer was distributed by 31 members of the Chinese Society of Breast Surgery between January 1,2018 and December 31,2018.Information was collected on tumor characteristics,treatment,mesh application,nipple-areola complex(NAC)preservation,postoperative complications,bilateral reconstruction,patient satisfaction and local recurrence.The overall rate of breast reconstruction was assessed,and the characteristics were compared across patient groups with different reconstruction approaches.Results:A total of 1,554 patients underwent breast reconstruction after total mastectomy,with a reconstruction rate of 9.6%.Among them,1,190 were implant-based,and 262 underwent autologous reconstructions,while 102 cases underwent a combination of both.Patients who underwent implant-based reconstruction were younger than those who received autologous reconstruction(40.1±4.6 vs.45.0±5.9,P=0.004).Compared to patients with autologous reconstruction,mesh application(25.5%vs.6.5%),NAC preservation(51.8%vs.40.5%)and reconstruction failure(1.8%vs.0)were more frequently reported among those with implant-based reconstruction.There was no significant difference in general satisfaction across three reconstruction approaches,though patients with autologous reconstruction reported the highest aesthetic satisfaction among the three groups(P=0.044).Conclusions:Implant-based breast reconstruction remains the dominant choice among patients,while autologous reconstruction was associated with higher aesthetic satisfaction.Our multi-center investigation based on the findings of the tertiary hospitals of Chinese Society of Breast Surgery may guide a future series of clinical studies on breast reconstruction in China.

Circular RNAs in breast cancer diagnosis,treatment and prognosis

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.

A machine learning model to predict efficacy of neoadjuvant therapy in breast cancer based on dynamic changes in systemic immunity

Objective:Neoadjuvant therapy(NAT)has been widely implemented as an essential treatment to improve therapeutic efficacy in patients with locally-advanced cancer to reduce tumor burden and prolong survival,particularly for human epidermal growth receptor 2-positive and triple-negative breast cancer.The role of peripheral immune components in predicting therapeutic responses has received limited attention.Herein we determined the relationship between dynamic changes in peripheral immune indices and therapeutic responses during NAT administration.Methods:Peripheral immune index data were collected from 134 patients before and after NAT.Logistic regression and machine learning algorithms were applied to the feature selection and model construction processes,respectively.Results:Peripheral immune status with a greater number of CD3^(+)T cells before and after NAT,and a greater number of CD8^(+)T cells,fewer CD4^(+)T cells,and fewer NK cells after NAT was significantly related to a pathological complete response(P<0.05).The post-NAT NK cell-to-pre-NAT NK cell ratio was negatively correlated with the response to NAT(HR=0.13,P=0.008).Based on the results of logistic regression,14 reliable features(P<0.05)were selected to construct the machine learning model.The random forest model exhibited the best power to predict efficacy of NAT among 10 machine learning model approaches(AUC=0.733).Conclusions:Statistically significant relationships between several specific immune indices and the efficacy of NAT were revealed.A random forest model based on dynamic changes in peripheral immune indices showed robust performance in predicting NAT efficacy.

Correction:Nanomaterial-Based Repurposing of Macrophage Metabolism and Its Applications

Following publication of the original article[1],the authors reported an error in the last author’s name,it was mistakenly written as“Jun Den”.The correct author’s name“Jun Deng”has been updated in this Correction.

ENST00000535926 is an unfavorable prognosis-related and tumorpromoting transcript of the CHPF gene in luminal A and B breast cancer

Chondroitin sulfate synthase 2(CHPF)is characterized as an oncogenic and poor prognosis-related gene in breast cancer.However,this gene has alternative splicing products encoding proteins of different lengths.Breast cancer is a group of heterogeneous tumors with distinct clinical and genomic characteristics.In this study,we explored the expression profile and prognostic value of the two transcripts of CHPF using data from The Cancer Genome Atlas(TCGA)-BRCA.The functional regulation of the two transcripts was also studied in MCF-7 and BT-474 cells.Among the two transcripts of CHPF,ENST00000535926 expression was significantly upregulated in the tumor samples and was the dominant isoform.ENST00000535926,but not ENST00000243776 upregulation,was associated with significantly worse progression-free survival(PFS)and disease-specific survival(DSS)in luminal A/B cases.However,no significant association was observed in PFS or DSS in other Prediction Analysis of Microarray 50(PAM50)subgroups.CHPF isoform 2 protein(encoded by ENST00000535926)significantly elevated the expression of P3H1 and RCN3 at the mRNA and protein levels in MCF-7 and BT-474 cells.The effect of ENST00000535926 was significantly stronger than ENST00000243776 in promoting tumor cell colony formation.The expression of P3H1 and RCN3 was negatively correlated with CD8+T cell infiltration but was positively correlated with cancer-associated fibroblast infiltration in luminal A/B tumors.In summary,this study revealed that ENST00000535926 is an unfavorable prognosis-related and tumor-promoting transcript of the CHPF gene in luminal A/B breast cancer.

Conceptualizing the complexity of ferroptosis to treat triple-negative breast cancer:theory-to-practice

Ferroptosis,a type of regulated cell death named one decade ago,is a unique type driven by lipid peroxidation in an iron-dependent manner.Ferroptosis differs radically from apoptosis and other regulated forms of cell death in both morphology and molecular underpinning.Ferroptosis can be triggered by a variety of physiologic conditions and pathologic stresses.There has been growing interest in ferroptosis in recent years,and research on ferroptosis is productive.

Insight into the evolution of breast cancer driven by genetic alterations

Breast cancer originates primarily from the epithelial cells of the mammary gland.Repeated mammary gland expansion and degeneration are accompanied by an increased risk of genetic alterations in the breast1.These mutations in breast epithelial cells dynamically occur in response to pregnancy,labor and delivery,breastfeeding,and the menstrual cycle,with a decline in mutation rates after menopause,which may be related to a decrease in estrogen levels.The breast epithelial cell mutations are also consistent with epidemiologic observations2.

Identification of an immune classifier for predicting the prognosis and therapeutic response in triple-negative breast cancer

Triple-negative breast cancer(TNBC)poses a significant challenge due to the lack of reliable prognostic gene signatures and an understanding of its immune behavior.Methods:We analyzed clinical information and mRNA expression data from 162 TNBC patients in TCGA-BRCA and 320 patients in METABRIC-BRCA.Utilizing weighted gene coexpression network analysis,we pinpointed 34 TNBC immune genes linked to survival.The least absolute shrinkage and selection operator Cox regression method identified key TNBC immune candidates for prognosis prediction.We calculated chemotherapy sensitivity scores using the“pRRophetic”package in R software and assessed immunotherapy response using the Tumor Immune Dysfunction and Exclusion algorithm.Results:In this study,34 survival-related TNBC immune gene expression profiles were identified.A least absolute shrinkage and selection operator-Cox regression model was used and 15 candidates were prioritized,with a concomitant establishment of a robust risk immune classifier.The high-risk TNBC immune groups showed increased sensitivity to therapeutic agents like RO-3306,Tamoxifen,Sunitinib,JNK Inhibitor VIII,XMD11-85h,BX-912,and Tivozanib.An analysis of the Search Tool for Interaction of Chemicals database revealed the associations between the high-risk group and signaling pathways,such as those involving Rap1,Ras,and PI3K-Akt.The low-risk group showed a higher immunotherapy response rate,as observed through the tumor immune dysfunction and exclusion analysis in the TCGA-TNBC and METABRIC-TNBC cohorts.Conclusion:This study provides insights into the immune complexities of TNBC,paving the way for novel diagnostic approaches and precision treatment methods that exploit its immunological intricacies,thus offering hope for improved management and outcomes of this challenging disease.