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.

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.

Combined peripheral natural killer cell and circulating tumor cell enumeration enhance prognostic efficiency in patients with metastatic triple-negative breast cancer

Objective：Triple-negative breast cancer（TNBC）is a heterogeneous disease with poor prognosis.Circulating tumor cells（CTCs）are a promising predictor for breast cancer prognoses but their reliability regarding progression-free survival（PFS）is controversial.We aim to verify their predictive value in TNBC.Methods：In present prospective cohort study,we used the Pep@MNPs method to enumerate CTCs in baseline blood samples from 75 patients with TNBC（taken at inclusion in this study）and analyzed correlations between CTC numbers and outcomes and other clinical parameters.Results：Median PFS was 6.0（range：1.0–25.0）months for the entire cohort,in whom we found no correlations between baseline CTC status and initial tumor stage（P=0.167）,tumor grade（P=0.783）or histological type（P=0.084）.However,among those getting first-line treatment,baseline CTC status was positively correlated with ratio of peripheral natural killer（NK）cells（P=0.032）,presence of lung metastasis（P=0.034）and number of visceral metastatic site（P=0.037）.Baseline CTC status was predictive for PFS in first-line TNBC（P=0.033）,but not for the cohort as a whole（P=0.118）.This prognostic limitation of CTC could be ameliorated by combining CTC and NK cell enumeration（P=0.049）.Conclusions：Baseline CTC status was predictive of lung metastasis,peripheral NK cell ratio and PFS in TNBC patients undergoing first-line treatment.We have developed a combined CTC-NK enumeration strategy that allows us to predict PFS in TNBC without any preconditions.

Decreased LDHB expression in breast tumor cells causes NK cell activation and promotes tumor progression

Objective: Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B(LDHB) has been detected in breast cancer but the function of LDHB remains unknown.Methods: Western blot was used to analyze LDHB expression in breast cancer cells. The impact of LDHB on tumor cell migration and invasion was determined using Transwell assays, wound healing assays, and a mouse lung metastasis model. Subcutaneous tumor formation, a natural killer(NK) cell cytotoxicity assay, and flow cytometry evaluated NK cell activation. Immunofluorescence and quantitative real-time PCR detected NK cell activation markers. Kaplan-Meier analysis evaluated the effect of immune cell infiltration on prognosis. Single-sample gene set enrichment analysis determined NK cell activation scores. A support vector machine predicted the role of LDHB in NK cell activation.Results: In this study we showed that LDHB inhibits the breast cancer cell metastasis and orchestrates metabolic reprogramming within tumor cells. Our results revealed that LDHB-mediated lactic acid clearance in breast cancer cells triggers NK cell activation within the tumor microenvironment. Our findings, which were confirmed in a murine model, demonstrated that LDHB in tumor cells promotes NK cell activation and ultimately results in the eradication of malignant cells. Clinically, our study further validated that LDHB affects immune cell infiltration and function. Specifically, its expression has been linked to enhanced NK cell-mediated cytotoxicity and improved patient survival. Furthermore, we identified LDHB expression in tumors as an important predictor of NK cell activation, with strong predictive ability in some cancers.Conclusions: Our results suggest that LDHB is a promising target for activating the tumor immune microenvironment in breast cancer, where LDHB-associated lactic acid clearance leads to increased NK cell activity. This study highlights the critical role of LDHB in regulating immune responses and its potential as a therapeutic target for breast cancer.

A Novel Approach to Breast Tumor Detection: Enhanced Speckle Reduction and Hybrid Classification in Ultrasound Imaging

Breast cancer detection heavily relies on medical imaging, particularly ultrasound, for early diagnosis and effectivetreatment. This research addresses the challenges associated with computer-aided diagnosis (CAD) of breastcancer fromultrasound images. The primary challenge is accurately distinguishing between malignant and benigntumors, complicated by factors such as speckle noise, variable image quality, and the need for precise segmentationand classification. The main objective of the research paper is to develop an advanced methodology for breastultrasound image classification, focusing on speckle noise reduction, precise segmentation, feature extraction, andmachine learning-based classification. A unique approach is introduced that combines Enhanced Speckle ReducedAnisotropic Diffusion (SRAD) filters for speckle noise reduction, U-NET-based segmentation, Genetic Algorithm(GA)-based feature selection, and Random Forest and Bagging Tree classifiers, resulting in a novel and efficientmodel. To test and validate the hybrid model, rigorous experimentations were performed and results state thatthe proposed hybrid model achieved accuracy rate of 99.9%, outperforming other existing techniques, and alsosignificantly reducing computational time. This enhanced accuracy, along with improved sensitivity and specificity,makes the proposed hybrid model a valuable addition to CAD systems in breast cancer diagnosis, ultimatelyenhancing diagnostic accuracy in clinical applications.

27-Hydroxycholesterol-induced EndMT acts via STAT3 signaling to promote breast cancer cell migration by altering the tumor microenvironment

Objective:The endothelial to mesenchymal transition(EndMT)plays a major role in cancer metastasis by regulating the complexity of the tumor microenvironment(TME).Here,we investigated whether 27-hydroxycholesterol(27 HC)induces EndMT in endothelial cells(ECs).Methods:EndMT markers in the human microvascular endothelial cell-1(HMEC-1)cell line and human umbilical vein endothelial cells(HUVECs)stimulated with 27 HC were evaluated with Western blot.Epithelial to mesenchymal transition(EMT)markers in breast cancer(BC)cells cultured in conditioned medium were investigated with quantitative real time polymerase chain reaction(qRT-PCR).The MMP-2 and MMP-9 mRNA expression and activity were detected with qRT-PCR and gelatin zymography assays,respectively.The effect of activated STAT3 on 27 HC-induced EndMT was validated by Western blot,immunofluorescence staining,and cell transfection assays.The migration ability of BC cells was evaluated with Transwell assays.Results:We found that 27 HC induced EndMT in HMEC-1 and HUVECs,and 27 HC-induced EndMT facilitated EMT and BC cell migration.The 27 HC-induced EMT of BC cells also promoted EndMT and HUVEC migration.Investigation of the underlying molecular mechanisms revealed that STAT3 knockdown repressed EndMT in HUVECs as well as migration in BC cells induced with 27 HC.In addition,C646 and resveratrol,inhibitors of STAT3 acetylation,repressed the expression of Ac-STAT3,p-STAT3,and EndMT markers in HUVECs exposed to 27 HC;these HUVECs in turn attenuated the migration ability of BC cells in 27 HC-induced EndMT.Conclusions:Cross-talk between 27 HC-induced EndMT and EMT was observed in the TME.Moreover,activation of STAT3 signaling was found to be involved in 27 HC-induced EndMT.

Research progress in tumor angiogenesis and drug resistance in breast cancer

Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, via exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.

Prognostic value of circulating tumor cells combined with neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma

BACKGROUND Circulating tumor cell(CTC)count and neutrophil-to-lymphocyte ratio(NLR)are both closely associated with the prognosis of hepatocellular carcinoma(HCC).AIM To investigate the prognostic value of combining these two indicators in HCC.METHODS Clinical data were collected from patients with advanced HCC who received im-mune therapy combined with targeted therapy at the Department of Oncology,the Affiliated Hospital of Southwest Medical University,Sichuan,China,from 2021 to 2023.The optimal cutoff values for CTC programmed death-ligand 1(PD-L1)(+)>1 or CTC PD-L1(+)≤1 and NLR>3.89 or NLR≤3.89 were evaluated using X-Tile software.Patients were categorized into three groups based on CTC PD-L1(+)counts and NLR:CTC-NLR(0),CTC-NLR(1),and CTC-NLR(2).The relationship between CTC-NLR and clinical variables as well as survival rates was assessed.RESULTS Patients with high CTC PD-L1(+)expression or NLR at baseline had shorter median progression-free survival(m-PFS)and median overall survival(mOS)than those with low levels of CTC PD-L1(+)or NLR(P<0.001).Mean-while,patients in the CTC-NLR(2)group showed a significant decrease in mPFS and mOS.Cox regression analysis revealed that alpha-fetoprotein(AFP),CTC PD-L1(+),and CTC-NLR were independent predictors of OS.The time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months(0.821)and 18 months(0.821)was superior to that of AFP and CTC PD-L1(+).CONCLUSION HCC patients with high CTC PD-L1(+)or NLR expression tend to exhibit poor prognosis,and a high baseline CTC-NLR score may indicate low survival.CTC-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.

Two Stages Segmentation Algorithm of Breast Tumor in DCE-MRI Based on Multi-Scale Feature and Boundary Attention Mechanism

Nuclearmagnetic resonance imaging of breasts often presents complex backgrounds.Breast tumors exhibit varying sizes,uneven intensity,and indistinct boundaries.These characteristics can lead to challenges such as low accuracy and incorrect segmentation during tumor segmentation.Thus,we propose a two-stage breast tumor segmentation method leveraging multi-scale features and boundary attention mechanisms.Initially,the breast region of interest is extracted to isolate the breast area from surrounding tissues and organs.Subsequently,we devise a fusion network incorporatingmulti-scale features and boundary attentionmechanisms for breast tumor segmentation.We incorporate multi-scale parallel dilated convolution modules into the network,enhancing its capability to segment tumors of various sizes through multi-scale convolution and novel fusion techniques.Additionally,attention and boundary detection modules are included to augment the network’s capacity to locate tumors by capturing nonlocal dependencies in both spatial and channel domains.Furthermore,a hybrid loss function with boundary weight is employed to address sample class imbalance issues and enhance the network’s boundary maintenance capability through additional loss.Themethod was evaluated using breast data from 207 patients at RuijinHospital,resulting in a 6.64%increase in Dice similarity coefficient compared to the benchmarkU-Net.Experimental results demonstrate the superiority of the method over other segmentation techniques,with fewer model parameters.

Prognostic tumor microenvironment gene and the relationship with immune infiltration characteristics in metastatic breast cancer

The aim of this study was to reveal genes associated with breast cancer metastasis,to investigate their intrinsic relationship with immune cell infiltration in the tumor microenvironment,and to screen for prognostic biomarkers.Gene expression data of breast cancer patients and their metastases were downloaded from the GEO,TCGA database.R language package was used to screen for differentially expressed genes,enrichment analysis of genes,PPI network construction,and also to elucidate key genes for diagnostic and prognostic survival.Spearman’s r correlation was used to analyze the correlation between key genes and infiltrating immune cells.We screened 25 hub genes,FN1,CLEC5A,ATP8B4,TLR7,LY86,PTGER3 and other genes were differentially expressed in cancer and paraneoplastic tissues.However,patients with higher expression of CD1C,IL-18 breast cancer had a better prognosis in the 10 years survival period,while patients with high expression of FN1,EIF4EBP1 tumors had a worse prognosis.In addition,TP53 and HIF1 genes are closely related to the signaling pathway of breast cancer metastasis.In this study,gene expression of ATP8B4 and CD1C were correlated with cancer tissue infiltration of CD8^(+)T lymphocytes,while GSE43816,GSE62327 and TCGA databases showed that CD8^(+)T lymphocytes were closely associated with breast cancer progression.Functional enrichment analysis of genes based on expression differences yielded key genes of prognostic value in the breast cancer microenvironment.

Cost analysis of radical resection of malignant breast tumors under the China Healthcare Security Diagnosis Related Groups payment system

BACKGROUND Breast cancer is one of the most common malignant tumors in women worldwide and poses a severe threat to their health.Therefore,this study examined patients who underwent breast cancer surgery,analyzed hospitalization costs and structure,and explored the impact of China Healthcare Security Diagnosis Related Groups(CHS-DRG)management on patient costs.It aimed to provide medical institutions with ways to reduce costs,optimize cost structures,reduce patient burden,and improve service efficiency.AIM To study the CHS-DRG payment system’s impact on breast cancer surgery costs.METHODS Using the CHS-DRG(version 1.1)grouping criteria,4073 patients,who underwent the radical resection of breast malignant tumors from January to December 2023,were included in the JA29 group;1028 patients were part of the CHS-DRG payment system,unlike the rest.Through an independent sample t-test,the length of hospital stay as well as total hospitalization,medicine and consumables,medical,nursing,medical technology,and management expenses were compared.Pearson’s correlation coefficient was used to test the cost correlation.RESULTS In terms of hospitalization expenses,patients in the CHS-DRG payment group had lower medical,nursing,and management expenses than those in the diagnosis-related group(DRG)non-payment group.For patients in the DRG payment group,the factors affecting the total hospitalization cost,in descending order of relevance,were medicine and consumable costs,consumable costs,medicine costs,medical costs,medical technology costs,management costs,nursing costs,and length of hospital stay.For patients in the DRG nonpayment group,the factors affecting the total hospitalization expenses in descending order of relevance were medicines and consumable expenses,consumable expenses,medical technology expenses,the cost of medicines,medical expenses,nursing expenses,length of hospital stay,and management expenses.CONCLUSION The CHS-DRG system can help control and reduce unnecessary medical expenses by controlling medicine costs,medical consumable costs,and the length of hospital stay while ensuring medical safety.

Analysis of the Effect of GINS4 Regarding the Proliferation and Invasion of Breast Cancer Cells

Objective: To analyze the role and influence of the GINS4 gene in breast cancer progression and to explore its expression in triple-negative and non-triple-negative breast cancer cell lines. Methods: Single-gene analysis of GINS4 was performed by breast cancer RNA transcriptome data from The Cancer Genome Atlas (TCGA). Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression of GINS4 in triple-negative and non-triple-negative breast cancer cell lines. The knockdown effects of GINS4 in MDA-MB-231 and MCF-7 cell lines on the proliferation and invasion of breast cancer cells were examined by cell counting kit 8 (CCK8) and Transwell assays. Results: Bioinformatics analysis showed that the expression of GINS4 in breast cancer was significantly higher than that in normal breast tissues (P > 0.05). At the same time, cell experiments confirmed that GINS4 was highly expressed in human breast cancer cell lines with normal breast cells as reference and in MDA-MB-231 and MCF-7 cell lines as reference, where the ability of proliferation and invasion of MDA-MB-231 and MCF-7 cells decreased after GINS4 knockdown. Conclusion: GINS4 is a gene associated with breast cancer malignancy, which can act as a novel tumor marker and has the potential as a new therapeutic target for breast cancer.

The breast cancer tumor microenvironment and precision medicine:immunogenicity and conditions favoring response to immunotherapy

Some main recent researches that have dissected tumor microenvironment(TME)by imaging mass cytometry(IMC)in different subtypes of primary breast cancer samples were considered.The many phenotypic variants,clusters of epithelial tumor and immune cells,their structural features as well as the main genetic aberrations,sub-clonal heterogeneity and their systematic classification also have been examined.Mutational evolution has been assessed in primary and metastatic breast cancer samples.Overall,based on these findings the current concept of precision medicine is questioned and challenged by alternative therapeutic strategies.In the last two decades,immunotherapy as a powerful and harmless tool to fight cancer has received huge attention.Thus,the tumor immune microenvironment(TIME)composition,its prognostic role for clinical course as well as a novel definition of immunogenicity in breast cancer are proposed.Investigational clinical trials carried out by us and other findings suggest that G0-G1 state induced in endocrine-dependent metastatic breast cancer is more suitable for successful immune manipulation.Residual micro-metastatic disease seems to be another specific condition that can significantly favor the immune response in breast and other solid tumors.

Value of Magnetic Resonance Imaging Texture Analysis in the Differential Diagnosis of Benign and Malignant Breast Tumors

Objective To investigate the difference in texture features on diffusion weighted imaging(DWI) images between breast benign and malignant tumors.Methods Patients including 56 with mass-like breast cancer, 16 with breast fibroadenoma, and 4 with intraductal papilloma of breast treated in the Hainan Hospital of Chinese PLA General Hospital were retrospectively enrolled in this study, and allocated to the benign group(20 patients) and the malignant group(56 patients) according to the post-surgically pathological results. Texture analysis was performed on axial DWI images, and five characteristic parameters including Angular Second Moment(ASM), Contrast, Correlation, Inverse Difference Moment(IDM), and Entropy were calculated. Independent sample t-test and Mann-Whitney U test were performed for intergroup comparison. Regression model was established by using Binary Logistic regression analysis, and receiver operating characteristic curve(ROC) analysis was carried out to evaluate the diagnostic efficiency. Results The texture features ASM, Contrast, Correlation and Entropy showed significant differences between the benign and malignant breast tumor groups(PASM= 0.014, Pcontrast= 0.019, Pcorrelation= 0.010, Pentropy= 0.007). The area under the ROC curve was 0.685, 0.681, 0.754, and 0.683 respectively for the positive texture variables mentioned above, and that for the combined variables(ASM, Contrast, and Entropy) was 0.802 in the model of Logistic regression. Binary Logistic regression analysis demonstrated that ASM, Contrast and Entropy were considered as thespecific imaging variables for the differential diagnosis of breast benign and malignant tumors.Conclusion The texture analysis of DWI may be a simple and effective tool in the differential diagnosis between breast benign and malignant tumors.

Role of tumor microenvironment in triple-negative breast cancer and its prognostic significance

Breast cancer has been shown to live in the tumor microenvironment, which consists of not only breast cancer cells themselves but also a significant amount of pathophysiologically altered surrounding stroma and cells. Diverse components of the breast cancer microenvironment, such as suppressive immune cells, re-programmed fibroblast cells, altered extracellular matrix (ECM) and certain soluble factors, synergistically impede an effective anti-tumor response and promote breast cancer progression and metastasis. Among these components, stromal cells in the breast cancer microenvironment are characterized by molecular alterations and aberrant signaling pathways, whereas the ECM features biochemical and biomechanical changes. However, triple-negative breast cancer (TNBC), the most aggressive subtype of this disease that lacks effective therapies available for other subtypes, is considered to feature a unique microenvironment distinct from that of other subtypes, especially compared to Luminal A subtype. Because these changes are now considered to significantly impact breast cancer development and progression, these unique alterations may serve as promising prognostic factors of clinical outcome or potential therapeutic targets for the treatment of TNBC. In this review, we focus on the composition of the TNBC microenvironment, concomitant distinct biological alteration, specific interplay between various cell types and TNBC cells, and the prognostic implications of these findings.

High Expression of p300 in Human Breast Cancer Correlates with Tumor Recurrence and Predicts Adverse Prognosis

Objective：Transcriptional coactivator p300 has been shown to play a variety of roles in the transcription process and mutation of p300 has been found in certain types of human cancers.However,the expression dynamics of p300 in breast cancer （BC） and its effect on BC patients＇ prognosis are poorly understood.Methods：In the present study,the methods of tissue microarray and immunohistochemistry （IHC） were used to investigate the protein expression of p300 in BCs.Receiver operating characteristic （ROC） curve analysis,Spearman＇s rank correlation,Kaplan-Meier plots and Cox proportional hazards regression model were utilized to analyze the data.Results：Based on the ROC curve analysis,the cutoff value for p300 high expression was defined when the H score for p300 was more than 105.High expression of p300 could be observed in 105/193 （54.4%） of BCs,in 6/25 （24.0%） of non-malignant breast tissues,respectively （P=0.004）.Further correlation analysis showed that high expression of p300 was positively correlated with higher histological grade,advanced clinical stage and tumor recurrence （P0.05）.In univariate survival analysis,a significant association between high expression of p300 and shortened patients＇ survival and poor progression-free survival was found （P0.05）.Importantly,p300 expression was evaluated as an independent prognostic factor in multivariate analysis （P0.05）.Conclusion：Our findings provide a basis for the concept that high expression of p300 in BC may be important in the acquisition of a recurrence phenotype,suggesting that p300 high expression,as examined by IHC,is an independent biomarker for poor prognosis of patients with BC.

Is breast conservative surgery a reasonable option in multifocal or multicentric tumors?

The incidence of multifocal(MF) and multicentric(MC) carcinomas varies widely among clinical studies,depending on definitions and methods for pathological sampling.Magnetic resonance imaging is increasingly used because it can help identify additional and conventionally occult tumors with high sensitivity.However,false positive lesions might incorrectly influence treatment decisions.Therefore,preoperative biopsies must be performed to avoid unnecessary surgery.Most studies have shown higher lymph node involvement rates in MF/MC tumors than in unifocal tumors.However,the rate of local recurrences is usually low after breast conservative treatment(BCT) of MC/MF tumors.It has been suggested that BCT is a reasonable option for MC/MF tumors in women aged 50-69 years,with small tumors and absence of extensive ductal carcinoma in situ.A metaanalysis showed an apparent decreased overall survival in MC/MF tumors but data are controversial.Surgery should achieve both acceptable cosmetic results and negative margins,which requires thorough preoperative radiological workup and localization of lesions.Boost radiotherapy techniques must be evaluated since double boosts might result in increased toxicity,namely fibrosis.In conclusion,BCT is feasible in selected patients with MC/MF but the choice of surgery must be discussed in a multidisciplinary team comprising at least radiologists,surgeons and radiotherapists.

Prognostic value of fibrinogen and D-dimer-fibrinogen ratio in resectable gastrointestinal stromal tumors

AIM To investigate the prognostic value of preoperative fbri-nogen concentration （FIB） and D-dimer-fibrinogen ratio （DFR） in gastrointestinal stromal tumors （GISTs）.METHODS The purpose of this study was to retrospectively ana-lyze 170 patients with GISTs who were admitted to our hospital from January 2010 to December 2015. The op-timal cutoff values of related parameters were estimated by receiver operating characteristic （ROC） curve analysis. The recurrence free survival （RFS） rate was evaluated using Kaplan-Meier curves. Univariate analysis and multivariate Cox regression models were used to analyze the prognostic factors of GISTs. The relationship between the FIB, D-dimer, DFR, platelet count （PLT）, and the clinicopathological features of GISTs was described by the chi-square test or nonparametric rank sum test （Mann-Whitney test）.RESULTS In ROC analysis, the optimal cutoff values of FIB, D-dimer, DFR, and PLT were 3.24 g/L, 1.24 mg/L, 0.354, and 197.5 （× 109/L）, respectively. Univariate analysis and the Kaplan-Meier survival curve showed that FIB, D-dimer, DFR, PLT,National Institutes of Health （NIH） risk category, tumor size, tumor location, and mitotic index were signifcantly relevant to the 3-year and 5-year survival rate of patients （ P 〈 0.05）. Cox multivariate regression analysis illustrated that FIB （RR： 0.108, 95%CI： 0.031-0.373）, DFR （RR： 0.319, 95%CI： 0.131-0.777）, and NIH risk category （ RR： 0.166, 95%CI： 0.047-0.589） were independent prognostic factors of the RFS rate （ P 〈 0. 05）. Moreover, FIB, D-dimer, DFR, and PLT were correlated with the clinical features of GISTs.CONCLUSIONFIB, D-dimer, DFR, and PLT are all related to the prognosis of GISTs. Moreover, FIB and DFR may be independent risk factors for predicting the prognosis of resectable GISTs.

Pattern response of dendritic cells in the tumor microenvironment and breast cancer

Breast cancer(BC) is the most common malignant neoplasm and the cause of death by cancer among women worldwide. Its development, including malignancy grade and patient prognosis, is influenced by various mutations that occur in the tumor cell and by the immune system's status, which has a direct influence on the tumor microenvironment and, consequently, on interactions with non-tumor cells involved in the immunological response. Among the immune response cells, dendritic cells(DCs) play a key role in the induction and maintenance of anti-tumor responses owing to their unique abilities for antigen cross-presentation and promotion of the activation of specific lymphocytes that target neoplasic cells. However, the tumor microenvironment can polarize DCs, transforming them into immunosuppressive regulatory DCs, a tolerogenicphenotype which limits the activity of effector T cells and supports tumor growth and progression. Various factors and signaling pathways have been implicated in the immunosuppressive functioning of DCs in cancer, and researchers are working on resolving processes that can circumvent tumor escape and developing viable therapeutic interventions to prevent or reverse the expression of immunosuppressive DCs in the tumor microenvironment. A better understanding of the pattern of DC response in patients with BC is fundamental to the development of specific therapeutic approaches to enable DCs to function properly. Various studies examining DCs immunotherapy have demonstrated its great potential for inducing immune responses to specific antigens and thereby reversing immunosuppression and related to clinical response in patients with BC. DCbased immunotherapy research has led to immense scientific advances, both in our understanding of the antitumor immune response and for the treatment of these patients.

Tumor microenvironment: driving forces and potential therapeutic targets for breast cancer metastasis

Distant metastasis to specific target organs is responsible for over 90%of breast cancer?related deaths,but the underlying molecular mechanism is unclear.Mounting evidence suggests that the interplay between breast cancer cells and the target organ microenvironment is the key determinant of organ?specific metastasis of this lethal disease.Here,we highlight new findings and concepts concerning the emerging role of the tumor microenvironment in breast cancer metastasis;we also discuss potential therapeutic intervention strategies aimed at targeting compo?nents of the tumor microenvironment.