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.

RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

Diagnostic challenges and individualized treatment of cervical adenocarcinoma metastases to the breast:A case report

BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized treatment.CASE SUMMARY A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node metastases.Cervical biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(PET/CT)did not show evidence of metastatic disease.She received concurrent cisplatin with external beam radiation therapy.Follow up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic disease.Patient was lost to follow up for six months.She was re-imaged on re-presentation and found to have widely metastatic disease including breast disease.Breast biopsy confirmed programmed death-ligand 1 positive metastatic cervical cancer.The patient received six cycles of carboplatin and paclitaxel with pembrolizumab.Restaging imaging demonstrated response.Patient continued on pembrolizumab with disease control.CONCLUSION Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis challenging.Clinical history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the breast.Overall,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.

Metochalcone induces senescence-associated secretory phenotype via JAK2/STAT3 pathway in breast cancer

Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.

Reversal of tamoxifen resistance by artemisinin in ER+breast cancer:bioinformatics analysis and experimental validation

Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.

Tumor deposits in axillary adipose tissue in patients with breast cancer:Do they matter?

Tumor deposits(TDs)are defined as discrete,irregular clusters of tumor cells lying in the soft tissue adjacent to but separate from the primary tumor,and are usually found in the lymphatic drainage area of the primary tumor.By definition,no residual lymph node structure should be identified in these tumor masses.At present,TDs are mainly reported in colorectal cancer,with a few reports in gastric cancer.There are very few reports on breast cancer(BC).For TDs,current dominant theories suggest that these are the result of lymph node metastasis of the tumor with complete destruction of the lymph nodes by the tumor tissue.Even some pathologists classify a TD as two lymph node metastases for calculation.Some pathologists also believe that TDs belong to the category of disseminated metastasis.Therefore,regardless of the origin,TDs are an indicator of poor prognosis.Moreover,for BC,sentinel lymph node biopsy is generally used at present.Whether radical axillary lymph node dissection should be adopted for BC with TDs in axillary lymph nodes is still inconclusive.The present commentary of this clinical issue has certain guiding significance.It is aimed to increase the awareness of the scientific community towards this under-recognized problem in BC pathology.

Prognostic factors of breast cancer brain metastasis

In this editorial we comment on the article by Chen et al published in the recent issue of the World Journal of Clinical Oncology.Brain metastasis is one of the most serious complications of breast cancer and causes high morbidity and mortality.Brain metastases may involve the brain parenchyma and/or leptomeninges.Symptomatic brain metastases develop in 10%-16%of newly recognized cases each year,and this rate increases to 30%in autopsy series.Depending on the size of the metastatic foci,it may be accompanied by extensive vasogenic edema or may occur as small tumor foci.Since brain metastases are a significant cause of morbidity and mortality,early diagnosis can have significant effects on survival and quality of life.The risk of developing brain metastases emerges progressively due to various patient and tumor characteristics.Patient variability may be particularly important in the susceptibility and distribution of brain metastases because malignant blood must cross the brain barrier and move within the brain parenchyma.Some characteristics of the tumor,such as gene expression,may increase the risk of brain metastasis.Clinical growth,tumor stage,tumor grade,growth receptor positivity,HER2 positivity,molecular subtype(such as triple negative status,luminal/nonluminal feature)increase the risk of developing breast cancer metastasis.Factors related to survival due to breast cancer brain metastasis include both tumor/patient characteristics and treatment characteristics,such as patient age,lung metastasis,surgery for brain metastasis,and HER2 positivity.If cases with a high risk of developing brain metastasis can be identified with the help of clinical procedures and artificial intelligence,survival and quality of life can be increased with early diagnosis and treatment.At the same time,it is important to predict the formation of this group in order to develop new treatment methods in cases with low survival expectancy with brain metastases.

Ferroptosis biomarkers predict tumor mutation burden's impact on prognosis in HER2-positive breast cancer

BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proliferation-related genes with prognosis in HER2+breast cancer(BC)patients is unclear.AIM To identify and evaluate fresh ferroptosis-related biomarkers for HER2+BC.METHODS First,we obtained the mRNA expression profiles and clinical information of HER2+BC patients from the TCGA and METABRIC public databases.A four gene prediction model comprising PROM2,SLC7A11,FANCD2,and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort.Patients were stratified into high-risk and low-risk groups based on their median risk score,an independent predictor of overall survival(OS).Based on these findings,immune infiltration,mutations,and medication sensitivity were analyzed in various risk groupings.Additionally,we assessed patient prognosis by combining the tumor mutation burden(TMB)with risk score.Finally,we evaluated the expression of critical genes by analyzing single-cell RNA sequencing(scRNA-seq)data from malignant vs normal epithelial cells.RESULTS We found that the higher the risk score was,the worse the prognosis was(P<0.05).We also found that the immune cell infiltration,mutation,and drug sensitivity were different between the different risk groups.The highrisk subgroup was associated with lower immune scores and high TMB.Moreover,we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses.HRisk-HTMB patients had the worst prognosis,whereas LRisk-LTMB patients had the best prognosis(P<0.0001).Analysis of the scRNAseq data showed that PROM2,SLC7A11,and FANCD2 were significantly differentially expressed,whereas FH was not,suggesting that these genes are expressed mainly in cancer epithelial cells(P<0.01).CONCLUSION Our model helps guide the prognosis of HER2+breast cancer patients,and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.

Hypoxia-mediated programmed cell death is involved in the formation of wooden breast in broilers

Background Wooden breast(WB)myopathy is a common myopathy found in commercial broiler chickens worldwide.Histological examination has revealed that WB myopathy is accompanied by damage to the pectoralis major(PM)muscle.However,the underlying mechanisms responsible for the formation of WB in broilers have not been fully elucidated.This study aimed to investigate the potential role of hypoxia-mediated programmed cell death(PCD)in the formation of WB myopathy.Results Histological examination and biochemical analysis were performed on the PM muscle of the control(CON)and WB groups.A significantly increased thickness of the breast muscle in the top,middle,and bottom portions(P<0.01)was found along with pathological structure damage of myofibers in the WB group.The number of capillaries per fiber in PM muscle,and the levels of p O_(2) and s O_(2) in the blood,were significantly decreased(P<0.01),while the levels of p CO_(2) and TCO_(2) in the blood were significantly increased(P<0.05),suggesting hypoxic conditions in the PM muscle of the WB group.We further evaluated the PCD-related pathways including autophagy,apoptosis,and necroptosis to understand the consequence response to enhanced hypoxic conditions in the PM muscle of birds with WB.The ratio of LC3 II to LC3 I,and the autophagy-related factors HIF-1α,BNIP3,Beclin1,AMPKα,and ULK1 at the m RNA and protein levels,were all significantly upregulated(P<0.05),showing that autophagy occurred in the PM muscle of the WB group.The apoptotic index,as well as the expressions of Bax,Cytc,caspase 9,and caspase 3,were significantly increased(P<0.05),whereas Bcl-2 was significantly decreased(P<0.05)in the WB-affected PM muscle,indicating the occurrence of apoptosis mediated by the mitochondrial pathway.Additionally,the expressions of necroptosis-related factors RIP1,RIP3,and MLKL,as well as NF-κB and the pro-inflammatory cytokines TNF-α,IL-1β,and IL-6,were all significantly enhanced(P<0.05)in the WB-affected PM muscle.Conclusions The WB myopathy reduces blood supply and induces hypoxia in the PM muscle,which is closely related to the occurrence of PCD including apoptosis,autophagy,and necroptosis within myofibers,and finally leads to abnormal muscle damage and the development of WB in broilers.

Normalized glandular dose coefficients for digital breast tomosynthesis using detailed Chinese breast models

The rise in breast cancer diagnoses among Chinese women has necessitated the use of X-ray breast screening,which carries a radiation risk.This study aimed to provide a dosimetry protocol for the Chinese female population to replace the traditional standard that utilizes simplified breast models,for the accurate estimation of the mean glandular dose of a patient undergoing digital breast tomosynthesis(DBT).The first set of detailed Chinese female breast models and representative breast parameters was constructed.Considering backscatter radiation and computational efficiency,we improved the combination of these models and the Chinese reference adult female whole-body voxel phantom.Image acquisition for four commercial DBT systems that are widely employed in China was simulated using the Monte Carlo method to obtain the normalized glandular dose coefficients of DBT(D_(gN)^(DBT))and the glandular depth dose(D_(g)^(dep)(z))for different breast characteristics and X-ray spectra.We calculated a series of D_(gN)^(DBT) values for breasts with different percentage mass glandularities(5%,25%,50%,75%,and 100%)and compressed breast thicknesses(2,3,4,5,6,and 7 cm)at various tube potentials(25,28,30,32,35,and 49 kV)and target/filter combinations(W/Rh,W/Al,Mo/Mo,Rh/Rh,and Rh/Ag).The parameter dependence of the breast characteristics and beam conditions on D_(gN)^(DBT) in detailed breast models was investigated.The D_(gN)^(DBT) results were 14.6-51.0%lower than those of the traditional dosimetry standard in China.The difference in D_(gN)^(DBT) was mainly due to a decrease in the depth of the main energy deposition area caused by the glandular distribution along the depth direction.The results obtained in this study may be used to improve breast dosimetry in China and provide more detailed information on risk assessment during DBT.

An advanced machine learning method for simultaneous breast cancer risk prediction and risk ranking in Chinese population:A prospective cohort and modeling study

Background:Breast cancer(BC)risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking.We aimed to develop risk-stratification models to predict long-and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods:The Breast Cancer Cohort Study in Chinese Women,a large ongoing prospective dynamic cohort study,includes 122,058 women aged 25-70 years old from the eastern part of China.We developed multiple machine-learning risk prediction models using parametric models(penalized logistic regression,bootstrap,and ensemble learning),which were the short-term ensemble penalized logistic regression(EPLR)risk prediction model and the ensemble penalized long-term(EPLT)risk prediction model to estimate BC risk.The models were assessed based on calibration and discrimination,and following this assessment,they were externally validated in new study participants from 2017 to 2020.Results:The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set.For the long-term EPLT risk prediction model,the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations,respectively.The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model(HCBCP)models for external validation was 0.193 and 0.233,respectively,indicating that the EPLT model has higher classification accuracy.Conclusions:We developed the EPLR and EPLT models to screen populations with a high risk of developing BC.These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase Ⅱ single-arm study

Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.

Associations between health-related fitness and patient-reported symptoms in newly diagnosed breast cancer patients

Background:Newly diagnosed breast cancer patients experience symptoms that may affect their quality of life,treatment outcomes,and survival.Preventing and managing breast cancer-related symptoms soon after diagnosis is essential.The purpose of this study was to investigate the associations between health-related fitness(HRF)and patient-reported symptoms in newly diagnosed breast cancer patients.Methods:This study utilized baseline data from the Alberta Moving Beyond Breast Cancer Cohort Study that were collected within 90 days of diagnosis.HRF measures included peak cardiopulmonary fitness(peak volume of oxygen consumption(VO_(2peak))),maximal muscular strength and endurance,flexibility,and body composition.Symptom measures included depression,sleep quality,and fatigue.Adjusted multivariable logistic regression was performed for analyses.Results:Of 1458 participants,51.5%reported poor sleep quality,26.5%reported significant fatigue,and 10.4%reported moderate depression.In multivariable-adjusted models,lower relative VO_(2peak)was independently associated with a greater likelihood of all symptom measures,including moderate depression(p<0.001),poor sleep quality(p=0.009),significant fatigue(p=0.008),any symptom(p<0.001),and multiple symptoms(p<0.001).VO_(2peak)demonstrated threshold associations with all symptom measures such that all 3 lower quartiles exhibited similar elevated risk compared to the highest quartile.The strength of the threshold associations varied by the symptom measure with odds ratios ranging from-1.5 for poor sleep quality to-3.0 for moderate depression and multiple symptoms.Moreover,lower relative upper body muscular endurance was also independently associated with fatigue in a dose-response manner(p=0.001),and higher body weight was independently associated with poor sleep quality in an inverted U pattern(p=0.021).Conclusion:Relative VO_(2peak)appears to be a critical HRF component associated with multiple patient-reported symptoms in newly diagnosed breast cancer patients.Other HRF parameters may also be important for specific symptoms.Exercise interventions targeting different HRF components may help newly diagnosed breast cancer patients manage specific symptoms and improve outcomes.

Progress and perspective of organoid technology in breast cancer research

Breast cancer,a malignant tumor with a high incidence in women,lacks in vitro research models that can represent the biological functions of breast tumors in vivo.As a new biological tool,the organoid model has unique advantages over traditional methods,such as cell culture and patient-derived xenografts.Combining organoids with other emerging technologies,such as gene engineering and microfluidic chip technology,provides an effective method to compensate for the deficiencies in organoid models of breast cancer in vivo.The emergence of breast cancer organoids has provided new tools and research directions in precision medicine,and drug research.In this review,we summarized the merits and demerits of organoids compared to traditional biological models,explored the latest developments in the combination of new technologies and organoid models,and discussed the construction methods and application prospects of different breast cancer organoid models.

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.

ACSL3 regulates breast cancer progression via lipid metabolism reprogramming and the YES1/YAP axis

Objective:Mitochondrial fatty acid oxidation is a metabolic pathway whose dysregulation is recognized as a critical factor in various cancers,because it sustains cancer cell survival,proliferation,and metastasis.The acyl-Co A synthetase long-chain(ACSL)family is known to activate long-chain fatty acids,yet the specific role of ACSL3 in breast cancer has not been determined.Methods:We assessed the prognostic value of ACSL3 in breast cancer by using data from tumor samples.Gain-of-function and lossof-function assays were also conducted to determine the roles and downstream regulatory mechanisms of ACSL3 in vitro and in vivo.Results:ACSL3 expression was notably downregulated in breast cancer tissues compared with normal tissues,and this phenotype correlated with improved survival outcomes.Functional experiments revealed that ACSL3 knockdown in breast cancer cells promoted cell proliferation,migration,and epithelial±mesenchymal transition.Mechanistically,ACSL3 was found to inhibitβ-oxidation and the formation of associated byproducts,thereby suppressing malignant behavior in breast cancer.Importantly,ACSL3 was found to interact with YES proto-oncogene 1,a member of the Src family of tyrosine kinases,and to suppress its activation through phosphorylation at Tyr419.The decrease in activated YES1 consequently inhibited YAP1 nuclear colocalization and transcriptional complex formation,and the expression of its downstream genes in breast cancer cell nuclei.Conclusions:ACSL3 suppresses breast cancer progression by impeding lipid metabolism reprogramming,and inhibiting malignant behaviors through phospho-YES1 mediated inhibition of YAP1 and its downstream pathways.These findings suggest that ACSL3 may serve as a potential biomarker and target for comprehensive therapeutic strategies for breast cancer.

Unraveling the complex landscape of endocrine resistance in breast cancer:Emerging role of long noncoding RNA AGPG and beyond

To the Editor:Breast cancer(BC)is the most common cancer in women,which affects 2.26 million people annually,with 680,000 fatalities.Around 70%of cases involve estrogen-activated estrogen receptors(ER),which promote tumor growth through gene regulation and cellular signaling.ER reactivation without ligands contributes to therapy resistance.Endocrine resistance in estrogen receptor-positive(ER+)breast tumors can result from mutations in ER,altered interactions with coactivators/corepressors,or crosstalk with growth factor receptors and oncogenic pathways.[1]Additionally,long non-coding RNAs(lncRNAs)are diverse molecules with distinct expression patterns in different cancer types,playing critical roles in tumorigenesis.[2]Notably,actin gamma 1 pseudogene(AGPG)is emerging as a noteworthy lncRNA that holds promise as a new therapeutic target intended for the effective management of endocrine-resistant BC.

Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown.Methods: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab.Results: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model.Conclusions: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.

Lindqvist-type Polyoxometalates Act as Anti-breast Cancer Drugs via Mitophagy-induced Apoptosis

Objective Lindqvist-type polyoxometalates(POMs)exhibit potential antitumor activities.This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism.Methods Using different cancer cell lines,the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains.Cell colony formation assay,autophagy detection,mitochondrial observation,qRT-PCR,Western blotting,and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism.Results MO-4,a Lindqvist-type POM linking a proline at its side strain,was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells.It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells.Mechanistically,MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species(ROS)levels and resulting in apoptosis.In vivo,breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment.Conclusion Collectively,the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.

Microstrip Patch Antenna with an Inverted T-Type Notch in the Partial Ground for Breast Cancer Detections

This study designs a microstrip patch antenna with an inverted T-type notch in the partial ground to detect tumorcells inside the human breast.The size of the current antenna is small enough(18mm×21mm×1.6mm)todistribute around the breast phantom.The operating frequency has been observed from6–14GHzwith a minimumreturn loss of−61.18 dB and themaximumgain of current proposed antenna is 5.8 dBiwhich is flexiblewith respectto the size of antenna.After the distribution of eight antennas around the breast phantom,the return loss curveswere observed in the presence and absence of tumor cells inside the breast phantom,and these observations showa sharp difference between the presence and absence of tumor cells.The simulated results show that this proposedantenna is suitable for early detection of cancerous cells inside the breast.