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.

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.

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.

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.

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.

Retraction:Downregulation of MicroRNA-449 Promotes Migration and Invasion of Breast Cancer Cells by Targeting Tumor Protein D52(TPD52)

Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.

Correction: Long non-coding RNA LINC02163 accelerates malignant tumor behaviors in breast cancer by regulating the microRNA-511-3p/HMGA2 axis as a competing endogenous RNA

In the article“Long non-coding RNA LINC02163 accelerates malignant tumor behaviors in breast cancer by regulating the microRNA-511-3p/HMGA2 axis as a competing endogenous RNA”(Oncology Research,2020,Vol.28,No.5,pp.483–495.doi:10.3727/096504020X15928179818438),there was an error in the processing of data.To further confirm our observation,we repeated multiple experiments involving in this study,including Flow Cytometry,Transwell Cell Migration and Invasion Assays,Xenograft Tumor Model,and Western Blotting.We have revised the figures to correct these errors.Corrected versions of the Figs.2,4,5,6,and 7 are provided.The corrections do not change any results or conclusion of the article.We apologize for any inconvenience caused.

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.

Single-cell analysis of tumor microenvironment and cell adhesion reveals that interleukin-1 beta promotes cancer cell proliferation in breast cancer

Background: Triple-negative breast cancer(TNBC), which is so called because of the lack of estrogen receptors(ER), progesterone receptors(PR), and human epidermal growth factor receptor 2(HER2) receptors on the cancer cells, accounts for 10%–15% of all breast cancers. The heterogeneity of the tumor microenvironment is high.However, the role of plasma cells controlling the tumor migration progression in TNBC is still not fully understood.Methods: We analyzed single-cell RNA sequencing data from five HER2 positive, 12ER positive/PR positive, and nine TNBC samples. The potential targets were validated by immunohistochemistry.Results: Plasma cells were enriched in TNBC samples, which was consistent with validation using data from The Cancer Genome Atlas. Cell communication analysis revealed that plasma cells interact with T cells through the intercellular adhesion molecule 2–integrin–aLb2 complex, and then release interleukin 1 beta(IL1B), as verified by immunohistochemistry, ultimately promoting tumor growth.Conclusion: Our results revealed the role of plasma cells in TNBC and identified IL1B as a new prognostic marker for TNBC.

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.

Predictive value of tumor-infiltrating lymphocytes for neoadjuvant therapy response in triple-negative breast cancer: A systematic review and meta-analysis

BACKGROUND The association between tumor-infiltrating lymphocyte(TIL)levels and the res-ponse to neoadjuvant therapy(NAT)in patients with triple-negative breast cancer(TNBC)remains unclear.AIM To investigate the predictive potential of TIL levels for the response to NAT in TNBC patients.METHODS A systematic search of the National Center for Biotechnology Information PubMed database was performed to collect relevant published literature prior to August 31,2023.The correlation between TIL levels and the NAT pathologic com-plete response(pCR)in TNBC patients was assessed using a systematic review and meta-analysis.Subgroup analysis,sensitivity analysis,and publication bias analysis were also conducted.RESULTS A total of 32 studies were included in this meta-analysis.The overall meta-ana-lysis results indicated that the pCR rate after NAT treatment in TNBC patients in the high TIL subgroup was significantly greater than that in patients in the low TIL subgroup(48.0%vs 27.7%)(risk ratio 2.01;95%confidence interval 1.77-2.29;P<0.001,I2=56%).Subgroup analysis revealed that the between-study hetero-geneity originated from differences in study design,TIL level cutoffs,and study populations.Publication bias could have existed in the included studies.The meta-analysis based on different NAT protocols revealed that all TNBC patients with high levels of TILs had a greater rate of pCR after NAT treatment in all protocols(all P≤0.01),and there was no significant between-protocol difference in the statistics among the different NAT protocols(P=0.29).Additionally,sensitivity analysis demonstrated that the overall results of the meta-analysis remained consistent when the included studies were individually excluded.CONCLUSION TILs can serve as a predictor of the response to NAT treatment in TNBC patients.TNBC patients with high levels of TILs exhibit a greater NAT pCR rate than those with low levels of TILs,and this predictive capability is con-sistent across different NAT regimens.

The prognostic role of circulating tumor DNA across breast cancer molecular subtypes:A systematic review and meta-analysis

Objective:Circulating tumor DNA(ctDNA)is increasingly being used as a potential prognostic biomarker in cancer patients.We aimed to assess the prognostic value of ctDNA in different subtypes of breast cancer patients throughout the whole treatment cycle.Materials and methods:PubMed,Web of Science,Embase,Cochrane Library,Scopus,and clinical trials.gov databases were searched from January 2016 to May 2022.The following search terms were used:ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma.Only studies written in English were included.The following pre-specified criteria should be met for inclusion:(i)original articles,conference abstracts,etc.;(ii)patients with breast cancer;(iii)ctDNA measurement;and(iv)clinical outcome data such as recurrence-free survival(RFS)and overall survival(OS).The random-effects model was preferred considering the potential het-erogeneity across studies.The main outcomes are ctDNA detection rate and postoperative long-term outcomes(RFS and OS).Results:A total of 24 studies were screened.At every measurement time,the ctDNA detection rate of the HR+subgroup was similar to that of the HR-subgroup(P=0.075;P=0.458;P=0.744;and P=0.578),and the ctDNA detection rate of the HER2+subgroup was similar to that of the HER2-subgroup(P=0.805;P=0.271;P=0.807;and P=0.703).In the HR+subgroup,RFS and OS of ctDNA positive patients were similar to those of ctDNA negative patients(P=0.589 and P=0.110),while RFS and OS of the ctDNA positive group was significantly shorter than those of the ctDNA negative patients in the HR-subgroup(HR=4.03,P<0.001;HR=3.21,P<0.001).According to HER grouping,the results were the same as above.In the triple negative breast cancer(TNBC)subgroup,the RFS and OS of ctDNA-positive patients was significantly shorter than of the ctDNA negative patients before and after surgery.Conclusions:ctDNA was more predictive of recurrence-free survival and overall survival in the HR-subgroup than in the HR+subgroup,and the same result was showed in the HER2-subgroup vs.HER2+subgroup.The prognosis of the TNBC subtype is closely related to ctDNA before and after surgery.

Circulating tumor DNA as prognostic markers of relapsed breast cancer:a systematic review and meta-analysis

Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognosis biomarker in patients of breast cancer. This review aims to assess the clinical value of ctDNA in outcome prediction in breast cancer patients throughout the whole treatment cycle. Methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov were searched from January 2016 to May 2022. Conference abstracts published in last three years were also included. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English languages were included. The following pre-specified criteria should be met for inclusion: (1) observational studies (prospective or retrospective), randomized control trials, case-control studies and case series studies;(2) patients with breast cancer;(3) ctDNA measurement;(4) clinical outcome data such as objective response rate (ORR), pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS), and so on. The random-effect model was preferred considering the potential heterogeneity across studies. The primary outcomes included postoperative short-term outcomes (ORR and pCR) and postoperative long-term outcomes (RFS, OS, and relapse). Secondary outcomes focused on ctDNA detection rate. Results: A total of 30 studies, comprising of 19 cohort studies, 2 case-control studies and 9 case series studies were included. The baseline ctDNA was significantly negatively associated with ORR outcome (Relative Risk [RR] = 0.65, 95% confidence interval [CI]: 0.50–0.83), with lower ORR in the ctDNA-positive group than ctDNAnegative group. ctDNA during neoadjuvant therapy (NAT) treatment was significantly associated with pCR outcomes (Odds Ratio [OR] = 0.15, 95% CI: 0.04–0.54). The strong association between ctDNA and RFS or relapse outcome was significant across the whole treatment period, especially after the surgery (RFS: Hazard Ratio [HR] = 6.74, 95% CI: 3.73–12.17;relapse outcome: RR = 7.11, 95% CI: 3.05–16.53), although there was heterogeneity in these results. Pre-operative and post-operative ctDNA measurements were significantly associated with OS outcomes (pre-operative: HR = 2.03, 95% CI: 1.12–3.70;post-operative: HR = 6.03, 95% CI: 1.31–27.78). Conclusions: In this review, ctDNA measurements at different timepoints are correlated with evaluation indexes at different periods after treatment. The ctDNA can be used as an early potential postoperative prognosis biomarker in breast cancer, and also as a reference index to evaluate the therapeutic effect at different stages.

Ipsilateral breast tumor recurrence in early stage breast cancer patients treated with breast conserving surgery and adjuvant radiation therapy: Concordance of biomarkers and tumor location from primary tumor to in-breast tumor recurrence

BACKGROUND Patients with an in-breast tumor recurrence(IBTR)after breast-conserving therapy have a high risk of distant metastasis and disease-related mortality.Classifying clinical parameters that increase risk for recurrence after IBTR remains a challenge.AIM To describe primary and recurrent tumor characteristics in patients who experience an IBTR and understand the relationship between these characteristics and disease outcomes.METHODS Patients with stage 0-II breast cancer treated with lumpectomy and adjuvant radiation were identified from institutional databases of patients treated from 2003-2017 at our institution.Overall survival(OS),disease-free survival,and local recurrence-free survival(LRFS)were estimated using the Kaplan Meier method.We identified patients who experienced an isolated IBTR.Concordance of hormone receptor status and location of tumor from primary to recurrence was evaluated.The effect of clinical and treatment parameters on disease outcomes was also evaluated.RESULTS We identified 2164 patients who met the eligibility criteria.The median follow-up for all patients was 3.73[interquartile range(IQR)2.27-6.07]years.Five-year OS was 97.7%(95%CI:96.8%-98.6%)with 28 deaths;5-year LRFS was 98.0%(97.2-98.8)with 31 IBTRs.We identified 37 patients with isolated IBTR,19(51.4%)as ductal carcinoma in situ and 18(48.6%)as invasive disease,of whom 83.3%had an in situ component.Median time from initial diagnosis to IBTR was 1.97(IQR:1.03-3.5)years.Radiotherapy information was available for 30 of 37 patients.Median whole-breast dose was 40.5 Gy and 23 patients received a boost to the tumor bed.Twenty-five of thirty-two(78.1%)patients had concordant hormone receptor status,HER-2 receptor status,and estrogen receptor(ER)(P=0.006)and progesterone receptor(PR)(P=0.001)status from primary to IBTR were significantly associated.There were no observed changes in HER-2 status from primary to IBTR.The concordance between quadrant of primary to IBTR was 10/19[(62.2%),P=0.008].Tumor size greater than 1.5 cm(HR=0.44,95%CI:0.22-0.90,P=0.02)and use of endocrine therapy upfront(HR=0.36,95%CI:0.18-0.73,P=0.004)decreased the risk of IBTR.CONCLUSION Among patients with early stage breast cancer who had breast conserving surgery treated with adjuvant RT,ER/PR status and quadrant were highly concordant from primary to IBTR.Tumor size greater than 1.5 cm and use of adjuvant endocrine therapy were significantly associated with decreased risk of IBTR.

Circulating tumor cells and circulating tumor DNA in breast cancer diagnosis and monitoring

Liquid biopsy,including both circulating tumor cells and circulating tumor DNA,is becoming more popular as a diagnostic tool in the clinical management of breast cancer.Elevated concentrations of these biomarkers during cancer treatment may be used as markers for cancer progression as well as to understand the mechanisms underlying metastasis and treatment resistance.Thus,these circulating markers serve as tools for cancer assessing and monitoring through a simple,non-invasive blood draw.However,despite several study results currently noting a potential clinical impact of ctDNA mutation tracking,the method is not used clinically in cancer diagnosis among patients and more studies are required to confirm it.This review focuses on understanding circulating tumor biomarkers,especially in breast cancer.

Dermatofibrosarcoma Protuberans—An Atypical Breast Tumor

A 49-year-old woman was referred to the Department of Plastic and Breast Surgery under suspicion of breast cancer after a mammogram revealed a self-discovered tumor in the lower part of her left breast. Clinical examination, mammography, and histopathological examination revealed that the original tumor in the left breast was benign, and an incidental malignant tumor, a dermatofibrosarcoma protuberans (DFSP), was found in the contralateral breast. DFSP is a rare and highly malignant entity that is often silent and difficult to diagnose, making a biopsy essential. Surgical treatment must be aggressive due to the high risk of recurrence, which constitutes a technical challenge. The patient underwent surgery using an oncoplastic approach with a volume-reducing technique to achieve the best possible therapeutic and aesthetic results. Therapeutic breast reduction was performed on the right breast and the tumor was removed within the resected tissue. A contralateral symmetrizing mammoplasty was also performed simultaneously. The patient was discharged without major complications, and no recurrence of the tumor was seen during the 30-month follow-up period. The surgical approach included alternative solutions in addition to conventional lumpectomy or mastectomy. A multidisciplinary, open-minded, and creative approach resulted in a satisfying outcome for this patient.

Characterization of spontaneous breast tumor in tree shrews(Tupaia belangeri chinenesis)

Breast cancer is a common malignant tumor.It is essential to develop suitable animal models for discovering novel preventive and therapeutic approaches.Tree shrews（Tupaia belangeri chinensis） have a closer evolutionary relationship with humans than do rodents,which have been widely used in laboratory research.Spontaneous breast tumors were identified in tree shrews in 1960s;however,no detailed studies about tree shrew breast tumors have been conducted to date.Here,we characterized a spontaneous breast tumor from tree shrews by Haematoxylin Eosin（HE） staining.This tumor was identified as a papillary tumor.Immunohistochemical staining（IHC） for progesterone receptor（PR）,Ki-67 and cleaved caspase-3 showed that tumor cells were positive for PR,highly proliferative,and less apoptotic compared to normal breast epithelial cells.Thus,the spontaneous tumor of tree shrew is very close to human papillary tumors in terms of morphology and pathology and we concluded that tree shrew may be a suitable animal model for breast cancer research.

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.

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.