Automatic detection of breast lesions in automated 3D breast ultrasound with cross-organ transfer learning

Background Deep convolutional neural networks have garnered considerable attention in numerous machine learning applications,particularly in visual recognition tasks such as image and video analyses.There is a growing interest in applying this technology to diverse applications in medical image analysis.Automated three dimensional Breast Ultrasound is a vital tool for detecting breast cancer,and computer-assisted diagnosis software,developed based on deep learning,can effectively assist radiologists in diagnosis.However,the network model is prone to overfitting during training,owing to challenges such as insufficient training data.This study attempts to solve the problem caused by small datasets and improve model detection performance.Methods We propose a breast cancer detection framework based on deep learning(a transfer learning method based on cross-organ cancer detection)and a contrastive learning method based on breast imaging reporting and data systems(BI-RADS).Results When using cross organ transfer learning and BIRADS based contrastive learning,the average sensitivity of the model increased by a maximum of 16.05%.Conclusion Our experiments have demonstrated that the parameters and experiences of cross-organ cancer detection can be mutually referenced,and contrastive learning method based on BI-RADS can improve the detection performance of the model.

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.

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.

UBE2T mediates the stemness properties of breast cancer cells through the mTOR signaling pathway

Objectives:This study aimed to reveal the role and possible mechanism of the ubiquitin-conjugating enzyme 2T(UBE2T)in the biological activities of breast cancer stem cells(BCSCs).Methods:The specific protein and gene expression were quantified by Western blotting and quantitative real-time polymerase chain reaction,the proportion of BCSCs was examined by flow cytometry,and the self-renewal and proliferation of BCSCs were verified by serial sphere formation and soft agar.Results:Increasing expression of UBE2T was drastically found in breast cancer than that in adjacent tissues.Furthermore,UBE2T overexpression significantly increased the proportion of BCSCs in breast cancer cells and promoted their self-renewal and proliferation.Silent UBE2T exhibited the opposite functions.UBE2T increased the levels of the mammalian target of rapamycin and the phosphorylated mammalian target of rapamycin.Mammalian target of rapamycin(mTOR)inhibitor rapamycin inhibited the function of UBE2T in BCSCs.Conclusion:UBE2T plays a role in BCSCs through mTOR pathway and may suggest a novel therapeutic strategy for breast cancer.

Magnetic resonance imaging findings of radiation-induced breast angiosarcoma:A case report

BACKGROUND Breast conservation surgery(BCS)with adjuvant radiotherapy has become a gold standard in the treatment of early-stage breast cancer,significantly reducing the risk of tumor recurrence.However,this treatment is associated with adverse effects,including the rare but aggressive radiation-induced angiosarcoma(RIAS).Despite its rarity and nonspecific initial presentation,RIAS presents a challenging diagnosis,emphasizing the importance of imaging techniques for early detection and accurate diagnosis.CASE SUMMARY We present a case of a 48-year-old post-menopausal woman who developed skin ecchymosis on the right breast seven years after receiving BCS and adjuvant radiotherapy for breast cancer.Initial mammography and ultrasound were inconclusive,showing post-treatment changes but failing to identify the underlying angiosarcoma.Contrast-enhanced breast magnetic resonance imaging(MRI)revealed diffuse skin thickening and nodularity with distinctive enhan-cement kinetics,leading to the diagnosis of RIAS.This case highlights the crucial role of MRI in diagnosing and determining the extent of RIAS,facilitating timely and appropriate surgical intervention.CONCLUSION Breast MRI is crucial for detecting RIAS,especially when mammography and ultrasound are inconclusive.

Breast Cancer in a Supernumerary Breast at the Yaoundé Gynaeco-Obstetric and Paediatric Hospital: About a Case

Accessory or ectopic breast tissue is an anomaly in the development of the breast. It is a rare condition that occurs along the embryological mammary line. In less than 1% of all breast cancers, supernumerary breast cancer is reported, with the axillary location being the most common in 60% to 90% of cases. Cancerous degeneration of this supernumerary breast tissue can pose a dual diagnostic and therapeutic problem. We report the case of locally advanced adenocarcinoma in a right supernumerary breast. This is a 75-year-old, grand-multiparous, postmenopausal, and known hypertensive patient on treatment. Family history was remarkable for brain cancer in her sister and oesophageal cancer in her mother. She consulted for a mass in the right axillary cavity on supernumerary breast evolving for a year. Clinical examination revealed a large, fixed, budding and haemorrhagic-ulcerated mass of the right axilla, with long axis measuring about 15 cm. There was as wella supernumerary breast on the left, but without particularity. A soft tissue ultrasound showed a large hypoechoicmass in the right axillary region of 116 mm with areas of central necrobiosis. Morphologically, the breasts were normal. A breast MRI revealed a subcutaneous mass in the right axillary cavity with skin ulceration and satellite lymphadenopathy. The extension assessment revealed liver metastases, and a biopsy of the mass revealed a breast adenocarcinoma. The case was the subject of a multidisciplinary consultation meeting following which a wide excision of the mass was indicated. The histo-pathology analysis results of the surgical specimen were in favour of a triple negative papillary adenocarcinoma. After a post-operative multidisciplinary consultation meeting, adjuvant chemotherapy was indicated. The development of supernumerary breasts depends on hormones, just like normal breasts. Breast cancer in accessory breast tissue is quite rare with the incidence being 6%. The most common pathology is invasive carcinoma (50% - 75%). It is usually located in the armpit (60% - 70%) although it can be present in other less common locations such as the inframammary region (5% - 10%) and rarely the thighs, perineum, groin and the vulva. Since accessory axillary breast tissue is not considered during breast screening examination, it is necessary for clinicians to be aware of this entity and associated pathologies. Their preventive excision in women at high risk can also be considered.

Clinicopathological features,psychological status,and prognosis of 33 patients with occult breast cancer

BACKGROUND Occult breast cancer(OBC)has traditionally been considered to be a carcinoma of unknown primary origin with a favorable prognosis and can be treated as stage II-III breast cancer.Due to the small number of cases and limited clinical experience,treatments vary greatly around the world and no standardized treatment has yet been established.AIM To investigate the clinicopathological features,psychological status and prognostic features of patients with OBC.METHODS The clinicopathological data of 33 OBC patients diagnosed and treated in the Affiliated Hospital of Xuzhou Medical University and Xuzhou Central Hospital from November 2015 to November 2022 were retrospectively analyzed.The psychological status of OBC patients was evaluated by the Self-rating Anxiety Scale and Self-rating Depression Scale.Patients’emotions,stress perception and psychological resilience were evaluated by the Positive and Negative Affect Schedule,the Chinese Perceived Stress Scale,and the Connor-Davidson Resilience Scale(CD-RISC),respectively.Patient survival was calculated using the Kaplan-Meier method,and survival curves were plotted for analysis with the log-rank test.Univariate and multivariate survival analyses were performed using the Cox regression model.RESULTS The 33 OBC patients included 32 females and 1 male.Of the 33 patients,30(91%)had axillary tumors,3(9%)had a neck mass as the primary symptom;18(54.5%)had estrogen receptor-positive tumors,17(51.5%)had progesterone receptor-positive tumors,and 18(54.5%)had Her-2-positive tumors;24(72.7%)received surgical treatment,including 18 patients who underwent modified radical mastectomy,1 patient who underwent breast-conserving surgery plus axillary lymph node dissection(ALND),and 5 patients who underwent ALND alone;12 patients received preoperative neoadjuvant therapy.All 30 patients developed anxiety and depression,with low positive affect scores and high negative affect scores,accompanied by a high stress level and poor psychological resilience.There were no differences in the psychological status of patients according to age,body mass index,or menopausal status.The overall survival and disease-free survival(DFS)of all the patients were 83.3%and 55.7%,respectively.Univariate analysis demonstrated that the initial tumor site(P=0.021)and node stage(P=0.020)were factors that may affect patient prognosis.The 5-year DFS rate of OBC patients who received radiotherapy was greater(P<0.001),while the use of different surgical methods(P=0.687)had no statistically significant effect on patient outcomes.Multivariate analysis revealed that radiotherapy(P=0.031)was an independent prognostic factor.Receiving radiotherapy had a significant effect on the CD-RISC score(P=0.02).CONCLUSION OBC is a rare breast disease whose diagnosis and treatment are currently controversial.There was no significant difference in the efficacy of other less invasive surgical procedures compared to those of modified radical mastectomy.In addition,radiotherapy can significantly improve patient outcomes.We should pay attention to the psychological state of patients while they receive antitumor therapy.

Effect of care intervention with a health education form for breastfeeding on breast distension,pain,and lactation in postpartum mothers

BACKGROUND Breastfeeding not only meets the nutritional needs of newborn growth and development but also promotes uterine contraction and discharge of lochia,which helps in maternal recovery.However,some mothers experience abnormal lactation and breast swelling due to a lack of breastfeeding knowledge,painful cesarean incisions,anesthesia,negative emotions,and other factors,resulting in a reduced breastfeeding rate,which adversely affects neonatal and maternal health.AIM To explore the effects of care intervention with a health education form for breastfeeding on breastfeeding-related conditions.METHODS In this study,207 mothers with postpartum breast pain and difficulty lactating were selected and divided into intervention and control groups using a random number table.Both groups of mothers were provided with basic nursing and related treatment measures after delivery.The intervention group additionally received care intervention with a health education form for breastfeeding.The scores of lactation volume,breast distension and pain,breastfeeding rate,breastfeeding self-efficacy,treatment effect,and complication rate of the two groups were compared.RESULTS After treatment,the breast pain score of the intervention group was significantly lower than that of the control group,while the lactation score,score of Breastfeeding Self-Efficacy Scale Short Form scale,parent-child communication score,maternal-infant interaction score,total score of maternal-infant communication,and breastfeeding rate of the intervention group were significantly higher than those of the control group.After intervention,the overall therapeutic effect of the intervention group was better than that of the control group,and the complication rate of the intervention group was lower than that of the control group.CONCLUSION Breastfeeding health education and nursing intervention combined with basic clinical treatment have good clinical effects in managing postpartum breast distension and pain and increasing lactation yield.

Bibliometric analysis of phosphoglycerate kinase 1 expression in breast cancer and its distinct upregulation in triple-negative breast cancer

BACKGROUND Phosphoglycerate kinase 1(PGK1)has been identified as a possible biomarker for breast cancer(BC)and may play a role in the development and advancement of triple-negative BC(TNBC).AIM To explore the PGK1 and BC research status and PGK1 expression and mecha-nism differences among TNBC,non-TNBC,and normal breast tissue.METHODS PGK1 and BC related literature was downloaded from Web of Science Core Co-llection Core Collection.Publication counts,key-word frequency,cooperation networks,and theme trends were analyzed.Normal breast,TNBC,and non-TNBC mRNA data were gathered,and differentially expressed genes obtained.Area under the summary receiver operating characteristic curves,sensitivity and specificity of PGK1 expression were determined.Kaplan Meier revealed PGK1’s prognostic implication.PGK1 co-expressed genes were explored,and Gene Onto-logy,Kyoto Encyclopedia of Genes and Genomes,and Disease Ontology applied.Protein-protein interaction networks were constructed.Hub genes identified.RESULTS PGK1 and BC related publications have surged since 2020,with China leading the way.The most frequent keyword was“Expression”.Collaborative networks were found among co-citations,countries,institutions,and authors.PGK1 expression and BC progression were research hotspots,and PGK1 expression and BC survival were research frontiers.In 16 TNBC vs non-cancerous breast and 15 TNBC vs non-TNBC datasets,PGK1 mRNA levels were higher in 1159 TNBC than 1205 non-cancerous breast cases[standardized mean differences(SMD):0.85,95%confidence interval(95%CI):0.54-1.16,I²=86%,P<0.001].PGK1 expression was higher in 1520 TNBC than 7072 non-TNBC cases(SMD:0.25,95%CI:0.03-0.47,I²=91%,P=0.02).Recurrence free survival was lower in PGK1-high-expression than PGK1-low-expression group(hazard ratio:1.282,P=0.023).PGK1 co-expressed genes were concentrated in ATP metabolic process,HIF-1 signaling,and glycolysis/gluconeogenesis pathways.CONCLUSION PGK1 expression is a research hotspot and frontier direction in the BC field.PGK1 may play a strong role in promoting cancer in TNBC by mediating metabolism and HIF-1 signaling pathways.

Navigating breast cancer brain metastasis:Risk factors,prognostic indicators,and treatment perspectives

In this editorial,we comment on the article by Chen et al.We specifically focus on the risk factors,prognostic factors,and management of brain metastasis(BM)in breast cancer(BC).BC is the second most common cancer to have BM after lung cancer.Independent risk factors for BM in BC are:HER-2 positive BC,triplenegative BC,and germline BRCA mutation.Other factors associated with BM are lung metastasis,age less than 40 years,and African and American ancestry.Even though risk factors associated with BM in BC are elucidated,there is a lack of data on predictive models for BM in BC.Few studies have been made to formulate predictive models or nomograms to address this issue,where age,grade of tumor,HER-2 receptor status,and number of metastatic sites(1 vs>1)were predictive of BM in metastatic BC.However,none have been used in clinical practice.National Comprehensive Cancer Network recommends screening of BM in advanced BC only when the patient is symptomatic or suspicious of central nervous system symptoms;routine screening for BM in BC is not recommended in the guidelines.BM decreases the quality of life and will have a significant psychological impact.Further studies are required for designing validated nomograms or predictive models for BM in BC;these models can be used in the future to develop treatment approaches to prevent BM,which improves the quality of life and overall survival.

Germline pathogenic variants among high hereditary risk patients with breast and ovarian cancer and unaffected subjects in Lebanese Arab women

BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.AIM To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.METHODS We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020.Data was collected and analyzed on Excel sheet.RESULTS In total,358 individuals were included,including 257 patients and 101 unaffected individuals with relatives with breast or ovarian cancer.The prevalence of breast cancer susceptibility gene(BRCA)1/2 pathogenic variants was 8.63%(19/220)in patients with breast cancer,and 15.1%(5/33)in those with ovarian cancer.Among the 25 of 220 patients with breast cancer tested by next-generation sequencing,3 patients had pathogenic variants other than BRCA1/2.The highest risk was observed in those aged 40 years with breast cancer and a positive family history,where the BRCA1/2 prevalence was 20.1%(9/43).Among the unaffected subjects,31.1%(14/45)had the same BRCA1/2 pathogenic variants in their corresponding relatives.Among the subjects referred because of a positive family history of cancer without known hereditary factors,5.35%(3/56)had pathogenic variants of BRCA1 and BRCA2.The c.131G>T nucleotide change was noted in one patient and two unrelated unaffected subjects with a BRCA1 pathogenic variant.CONCLUSION This study showed a 8.63%prevalence of pathogenic variants in patients with breast cancer and a 15.1%prevalence in patients with ovarian cancer.Among the relatives of patients with BRCA1/2 pathogenic variants,31%tested positive for the same variant,while 5.3%of subjects who tested positive due to a family history of breast cancer had a BRCA pathogenic variant.

Eribulin in breast cancer:Current insights and therapeutic perspectives

Eribulin is a non-taxane synthetic analogue approved in many countries as thirdline treatment for the treatment of patients with metastatic breast cancer.In addition to its mitotic property,eribulin has non-mitotic properties including but not limited to,its ability to induce phenotypic reversal of epithelial to mesenchymal transition,vascular remodelling,reduction in immunosuppressive tumour microenvironment.Since approval,there has been a surge in studies investigating the application of eribulin as an earlier-line treatment and also in combination with other agents such as immunotherapy and targeted therapy across all breast cancer sub-types,including hormone receptor positive,HER2 positive and triple negative breast cancer,many demonstrating promising activity.This review will focus on the application of eribulin in the treatment of metastatic breast cancer across all subtypes including its role as an earlier-line agent,its toxicity profile,and potential future directions.

Poland Syndrome: Breast Reconstruction Outcomes in 10 Years (2013-2023)

Summary: Poland syndrome is a rare congenital anomaly characterized by the partial or complete absence of the pectoralis major muscle and a wide spectrum of thoracic anomalies, predominantly on the ipsilateral side. These anomalies include hypoplasia or aplasia of the breast and its components, hypotrophy of subcutaneous fat, and absence of axillary hair, as well as hand deformities that can range from syndactyly to ectrodactyly. The aim of this study was to gather information about patients diagnosed with Poland syndrome at the Central South High Specialty Hospital of Petróleos Mexicanos over a period of 10 years and to identify their reconstructive algorithm. Materials and Methods: A retrospective, observational, and descriptive study was conducted to identify the population diagnosed with Poland syndrome at the “Central South High Specialty Hospital of Petróleos Mexicanos” during the period from 2013 to 2023. Results: The database of patients with Poland syndrome from 2013 to 2023 was analyzed, identifying a total of 8 patients with this diagnosis. Of these, 7 were women (90%) and 1 was a man (10%). The left side was more frequently affected (80%) compared to the right side (20%). The average reconstructive process required two surgical stages, mainly consisting of breast expander reconstruction (first stage) and replacement of the expander with an implant (second stage). Conclusions: Despite being a rare congenital condition, the volume of patients treated at the Central South High Specialty Hospital allows for improved diagnosis and contributes to their reconstructive process. The lack of diagnosis in the male population is notable, likely due to the absence of adequate screening.

Study on the Impact of Post-Mastectomy Radiotherapy on Immediate Breast Reconstruction and Complications: A Meta-Analysis

Background and objective:Immediate breast reconstruction not only reduces the number of surgeries for patients after mastectomy but also decreases psychological and physical trauma,making it increasingly popular.However,there is currently no consensus on the integration of post-mastectomy radiotherapy(PMRT)with reconstruction techniques.This review evaluates the impact of PMRT on complications following immediate breast reconstruction,providing guidance for clinical treatment decisions.Methods:PubMed,Web of Science,Embase,and other databases were searched for studies published in the past 15 years on outcomes of implant-based breast reconstruction in the context of radiotherapy to identify articles for analysis.RevMan 5.4 software was used to analyze the risks of seroma,infection,wound dehiscence,flap necrosis,implant exposure,capsule contracture,and reconstruction failure.Results:A total of 1l relevant studies were included,comprising 6323 cases of immediate breast reconstruction.It was found that breasts receiving postoperative irradiation had a significantly increased risk of complications,with statistically significant differences in seroma(P=0.004),infection(P<0.00001),wound dehiscence(P=0.04),implant exposure(P<0.00001),capsule contracture(P<0.00001),and reconstruction failure(P<0.00001).There was no statistically significant difference in flap necrosis(P=0.88).Conclusion:The results indicate that postoperative radiotherapy significantly increases the risk of complications for patients undergoing immediate implant-based reconstruction.Preventive measures may be taken in advance with the assistance of healthcare providers if necessary.

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.

Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.