Objective:Recurrence continues to be a pivotal challenge among hormone receptor-positive(HR^(+))/human epidermal growth factor receptor 2^(−)negative(HER2^(−))breast cancers.In the international consensus guidelines,H...Objective:Recurrence continues to be a pivotal challenge among hormone receptor-positive(HR^(+))/human epidermal growth factor receptor 2^(−)negative(HER2^(−))breast cancers.In the international consensus guidelines,HR^(+)/HER2^(−)breast cancer relapse patterns are divided into three distinct types:primary resistant,secondary resistant,and endocrine sensitive.However,owing to the lack of cohorts with treatment and follow-up data,the heterogeneity among different recurrence patterns remains uncharted.Current treatments still lack precision.Methods:This analysis included data from a large-scale multiomics study of a HR^(+)/HER2^(−)breast cancer cohort(n=314).Through the analysis of transcriptomics(n=312),proteomics(n=124),whole-exome sequencing(n=290),metabolomics(n=217),and digital pathology(n=228)data,we explored distinctive molecular features and identified putative therapeutic targets for patients experiencing recurrence.Results:We explored distinct clinicopathological characteristics,biological heterogeneity,and potential therapeutic strategies for recurrence.Based on a shared relapse signature,we stratified patients into high-and lowrecurrence-risk groups.Patients with different relapse patterns presented unique molecular features in primary tumors.Specifically,receptor tyrosine kinase(RTK)pathway activation in the primary resistant group suggested the utility of RTK inhibitors,whereas mammalian target of rapamycin(mTOR)and cell cycle pathway activation in the secondary resistant group highlighted the potential of mTOR and CDK4/6 inhibitors.Interestingly,the endocrine-sensitive group displayed a quiescent state and high genomic instability,suggesting that targeting quiescent cells and using poly-ADP-ribose polymerase(PARP)inhibitors could be effective strategies.Conclusions:These findings illuminate the clinicopathological and molecular landscape of HR^(+)/HER2^(−)breast cancer patients with distinct recurrence patterns,highlighting potential targeted therapies.展开更多
Objective:Triple-negative breast cancer(TNBC)is a heterogeneous and aggressive cancer.Although our previous study classified primary TNBC into four subtypes,comprehensive longitudinal investigations are lacking.Method...Objective:Triple-negative breast cancer(TNBC)is a heterogeneous and aggressive cancer.Although our previous study classified primary TNBC into four subtypes,comprehensive longitudinal investigations are lacking.Methods:We assembled a large-scale,real-world cohort comprised of 880 TNBC patients[465 early-stage TNBC(eTNBC)and 415 metastatic TNBC(mTNBC)patients]who were treated at Fudan University Shanghai Cancer Center.The longitudinal dynamics of TNBC subtypes during disease progression were elucidated in this patient cohort.Comprehensive analysis was performed to compare primary and metastatic lesions within specific TNBC subtypes.Results:The recurrence and metastasis rates within 3 years after initial diagnosis in the eTNBC cohort were 10.1%(47/465).The median overall survival(OS)in the mTNBC cohort was 27.2 months[95%confidence interval(CI),24.4–30.2 months],which indicated a poor prognosis.The prognostic significance of the original molecular subtypes in both eTNBC and mTNBC patients was confirmed.Consistent molecular subtypes were maintained in 77.5%of the patients throughout disease progression with the mesenchymal-like(MES)subtype demonstrating a tendency for subtype transition and brain metastasis.Additionally,a precision treatment strategy based on the metastatic MES subtype of target lesions resulted in improved progression-free survival in the FUTURE trial.Conclusions:Our longitudinal study comprehensively revealed the clinical characteristics and survival of patients with the original TNBC subtypes and validated the consistency of most molecular subtypes throughout disease progression.However,we emphasize the major importance of repeat pathologic confirmation of the MES subtype.展开更多
Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)cons...Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and differentiation.Studies have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast cancer.The tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ability.Hence,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer metastasis.In this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory mechanisms.Furthermore,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during metastasis.Overall,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.展开更多
Objective:Mammographic calcifications are a common feature of breast cancer,but their molecular characteristics and treatment implications in hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-neg...Objective:Mammographic calcifications are a common feature of breast cancer,but their molecular characteristics and treatment implications in hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-negative(HER2−)breast cancer remain unclear.Methods:We retrospectively collected mammography records of an HR+/HER2−breast cancer cohort(n=316)with matched clinicopathological,genomic,transcriptomic,and metabolomic data.On the basis of mammographic images,we grouped tumors by calcification status into calcification-negative tumors,tumors with probably benign calcifications,tumors with calcification of lowmoderate suspicion for maligancy and tumors with calcification of high suspicion for maligancy.We then explored the molecular characteristics associated with each calcification status across multiple dimensions.Results:Among the different statuses,tumors with probably benign calcifications exhibited elevated hormone receptor immunohistochemical staining scores,estrogen receptor(ER)pathway activation,lipid metabolism,and sensitivity to endocrine therapy.Tumors with calcifications of high suspicion for malignancy had relatively larger tumor sizes,elevated lymph node metastasis incidence,Ki-67 staining scores,genomic instability,cell cycle pathway activation,and may benefit from cyclin-dependent kinase 4 and 6(CDK4/6)inhibitors.Conclusions:Our research established links between tumor calcifications and molecular features,thus proposing potential precision treatment strategies for HR+/HER2−breast cancer.展开更多
Objective:Sentinel lymph node biopsy(SLNB)is currently the standard of care in clinically node negative(cN0)breast cancer.The present study aimed to evaluate the negative predictive value(NPV)of 18F-FDG dedicated lymp...Objective:Sentinel lymph node biopsy(SLNB)is currently the standard of care in clinically node negative(cN0)breast cancer.The present study aimed to evaluate the negative predictive value(NPV)of 18F-FDG dedicated lymph node positron emission tomography(LymphPET)in cN0 patients.Methods:This was a prospective phase II trial divided into 2 stages(NCT04072653).In the first stage,cN0 patients underwent axillary LymphPET followed by SLNB.In the second stage,SLNB was omitted in patients with a negative preoperative axillary assessment after integration of LymphPET.Here,we report the results of the first stage.The primary outcome was the NPV of LymphPET to detect macrometastasis of lymph nodes(LN-macro).Results:A total of 189 patients with invasive breast cancer underwent LymphPET followed by surgery with definitive pathological reports.Forty patients had LN-macro,and 16 patients had only lymph node micrometastasis.Of the 131 patients with a negative LymphPET result,16 patients had LN-macro,and the NPV was 87.8%.After combined axillary imaging evaluation with ultrasound and LymphPET,100 patients were found to be both LymphPET and ultrasound negative,9 patients had LN-macro,and the NPV was 91%.Conclusions:LymphPET can be used to screen patients to potentially avoid SLNB,with an NPV>90%.The second stage of the SOAPET trial is ongoing to confirm the safety of omission of SLNB according to preoperational axillary evaluation integrating LymphPET.展开更多
Objective:This study aimed to assess the efficacy and safety of various neoadjuvant regimens for patients diagnosed with early-stage or locally advanced triple-negative breast cancer(TNBC).Methods:Medline,EMBASE,Cochr...Objective:This study aimed to assess the efficacy and safety of various neoadjuvant regimens for patients diagnosed with early-stage or locally advanced triple-negative breast cancer(TNBC).Methods:Medline,EMBASE,Cochrane Library,and Web of Science were searched in May 2020 to identify randomized controlled trials(RCTs).Bayesian network meta-analysis(NMA)was performed(Registration:PROSPERO CRD42020223012).Results:A total of 35 RCTs involving 8,424 participants were reviewed,of which 22 RCTs with 5,203 patients were included in this NMA focusing on pathologic complete response(pCR).An anthracycline-taxane-based(AT)regimen combined with a platinum(ATPt)[odds ratio(OR)=2.04,95%credible interval(CrI):1.69,2.48]regimen,and a docetaxel regimen combined with a carboplatin(TCb;OR=2.16,95%CrI:1.20,3.91)regimen improved pCR beyond that with AT only.AT and ATPt combined with targeted therapy[including bevacizumab(Bev),veliparib,atezolizumab,or pembrolizumab]also improved pCR.Five RCTs included in this NMA reported serious adverse events(SAEs)or grade≥3 AEs.TCb was associated with fewer grade≥3 AEs than was AT(OR=0.66,95%CrI:0.23,1.72)alone.In contrast,ATPt,AT+Bev,ATPt+Bev,ATPt+veliparib,and ATPt+pembrolizumab were associated with more SAEs than was AT alone.Conclusions:In patients with TNBC,platinum-based neoadjuvant regimens ATPt and TCb increase pCR beyond that with AT alone,but TCb appears to be better tolerated than either AT or ATPt.Platinum-based regimens combined with targeted therapies(Bev,PARPi,and PD-1/PD-L1 inhibitor)also improve the pCR rate beyond that with AT alone,but this benefit is accompanied by greater toxicity.展开更多
The concept of antibody±drug conjugations(ADCs)can be tracked back to the early 20^(th) century when the renowned immunologist,Paul Ehrlich,proposed the idea of a"magic bullet",which utilizes ADCs for t...The concept of antibody±drug conjugations(ADCs)can be tracked back to the early 20^(th) century when the renowned immunologist,Paul Ehrlich,proposed the idea of a"magic bullet",which utilizes ADCs for targeted destruction of microorganisms and tumor cells^(1).After nearly one century of development,ADCs have emerged as a rather promising approach in the treatment of cancer,especially breast cancer,which is the most common malignant tumor in women^(2).展开更多
Ferroptosis,a type of regulated cell death named one decade ago,is a unique type driven by lipid peroxidation in an iron-dependent manner.Ferroptosis differs radically from apoptosis and other regulated forms of cell ...Ferroptosis,a type of regulated cell death named one decade ago,is a unique type driven by lipid peroxidation in an iron-dependent manner.Ferroptosis differs radically from apoptosis and other regulated forms of cell death in both morphology and molecular underpinning.Ferroptosis can be triggered by a variety of physiologic conditions and pathologic stresses.There has been growing interest in ferroptosis in recent years,and research on ferroptosis is productive.展开更多
Breast cancer is the most common malignant tumor in Chinese women,and its incidence is increasing.Regular screening is an effective method for early tumor detection and improving patient prognosis.In this review,we an...Breast cancer is the most common malignant tumor in Chinese women,and its incidence is increasing.Regular screening is an effective method for early tumor detection and improving patient prognosis.In this review,we analyze the epidemiological changes and risk factors associated with breast cancer in China and describe the establishment of a screening strategy suitable for Chinese women.Chinese patients with breast cancer tend to be younger than Western patients and to have denser breasts.Therefore,the age of initial screening in Chinese women should be earlier,and the importance of screening with a combination of ultrasound and mammography is stressed.Moreover,Chinese patients with breast cancers have several ancestry-specific genetic features,and aiding in the determination of genetic screening strategies for identifying high-risk populations.On the basis of current studies,we summarize the development of risk-stratified breast cancer screening guidelines for Chinese women and describe the significant improvement in the prognosis of patients with breast cancer in China.展开更多
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 ca...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.展开更多
Breast cancer susceptibility gene 1(BRCA1)is a tumor suppressor gene,and its protein BRCA1 plays a role in DNA repair[1].BRCA1 is generally expressed in the cells of mammary glands and other tissues,helping to repair ...Breast cancer susceptibility gene 1(BRCA1)is a tumor suppressor gene,and its protein BRCA1 plays a role in DNA repair[1].BRCA1 is generally expressed in the cells of mammary glands and other tissues,helping to repair damaged DNA or disrupting cells when DNA cannot be repaired.When BRCA1 is mutated and cannot function and therefore the damaged DNA cannot be repaired展开更多
The RNA component of mitochondrial RNA-processing endoribonuclease(RMRP)was first described as an entity that cleaved mitochondrial RNA at a priming site of mitochondrial DNA replication.This long noncoding RNA(lncRNA...The RNA component of mitochondrial RNA-processing endoribonuclease(RMRP)was first described as an entity that cleaved mitochondrial RNA at a priming site of mitochondrial DNA replication.This long noncoding RNA(lncRNA)was encoded by an evolutionarily conserved nuclear gene that has been characterized in many species,including human,mouse,cattle,zebrafish,toad,and yeast.It was soon learned that RMRP as a component of the RNase MRP complex was also located in the nucleus,and was critical for ribosomal RNA(rRNA)processing,particularly the biosynthesis of 5.8S rRNAs.In 2001,the first evidence of the role of RMRP in the pathogenesis of human disorders was reported,involving mutations in the RMRP gene,which caused cartilage-hair hypoplasia(CHH)1,a recessively inherited developmental disorder characterized by short stature,hypoplastic anemia,defective immunity,and predisposition to several cancers.展开更多
Metabolic remodeling is a key feature of cancer development.Knowledge of cancer metabolism has greatly expanded since the first observation of abnormal metabolism in cancer cells,the so-called Warburg effect.Malignant...Metabolic remodeling is a key feature of cancer development.Knowledge of cancer metabolism has greatly expanded since the first observation of abnormal metabolism in cancer cells,the so-called Warburg effect.Malignant cells tend to modify cellular metabolism to favor specialized fermentation over the aerobic respiration usually used by most normal cells.Thus,targeted cancer therapies based on reprogramming nutrient or metabolite metabolism have received substantial attention both conceptually and in clinical practice.In particular,the management of nutrient availability is becoming more attractive in cancer treatment.In this review,we discuss recent findings on tumor metabolism and potential dietary interventions based on the specific characteristics of tumor metabolism.First,we present a comprehensive overview of changes in macronutrient metabolism.Carbohydrates,amino acids,and lipids,are rewired in the cancer microenvironment individually or systematically.Second,we summarize recent progress in cancer interventions applying different types of diets and specific nutrient restrictions in pre-clinical research or clinical trials.展开更多
Breast cancer metastasis remains the leading cause of mortality in patients,yet its mechanisms are poorly understood.A recent Cell paper highlights the pivotal role of the proprotein convertase subtilisin/kexin type 9...Breast cancer metastasis remains the leading cause of mortality in patients,yet its mechanisms are poorly understood.A recent Cell paper highlights the pivotal role of the proprotein convertase subtilisin/kexin type 9(PCSK9)V474I germline variant in driving metastatic progression through suppression of the low-density lipoprotein receptor-related protein 1(LRP1)receptor,revealing novel therapeutic opportunities and genetic insights.展开更多
Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype.Molecular stratification and target therapy bring clinical benefit for TNBC patients,but it is difficult to implement comprehensive mole...Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype.Molecular stratification and target therapy bring clinical benefit for TNBC patients,but it is difficult to implement comprehensive molecular testing in clinical practice.Here,using our multi-omics TNBC cohort(N=425),a deep learning-based framework was devised and validated for comprehensive predictions of molecular features,subtypes and prognosis from pathological whole slide images.The framework first incorporated a neural network to decompose the tissue on WSIs,followed by a second one which was trained based on certain tissue types for predicting different targets.Multi-omics molecular features were analyzed including somatic mutations,copy number alterations,germline mutations,biological pathway activities,metabolomics features and immunotherapy biomarkers.It was shown that the molecular features with therapeutic implications can be predicted including the somatic PIK3CA mutation,germline BRCA2 mutation and PD-L1 protein expression(area under the curve[AUC]:0.78,0.79 and 0.74 respectively).The molecular subtypes of TNBC can be identified(AUC:0.84,0.85,0.93 and 0.73 for the basal-like immune-suppressed,immunomodulatory,luminal androgen receptor,and mesenchymal-like subtypes respectively)and their distinctive morphological patterns were revealed,which provided novel insights into the heterogeneity of TNBC.A neural network integrating image features and clinical covariates stratified patients into groups with different survival outcomes(log-rank P<0.001).Our prediction framework and neural network models were externally validated on the TNBC cases from TCGA(N=143)and appeared robust to the changes in patient population.For potential clinical translation,we built a novel online platform,where we modularized and deployed our framework along with the validated models.It can realize real-time one-stop prediction for new cases.In summary,using only pathological WSIs,our proposed framework can enable comprehensive stratifications of TNBC patients and provide valuable information for therapeutic decision-making.It had the potential to be clinically implemented and promote the personalized management of TNBC.展开更多
Background:Triple‐negative breast cancer(TNBC)displays high heterogeneity.The majority of TNBC cases are characterized by high Ki‐67 expression.TNBC with low Ki‐67 expression accounts for only a small fraction of c...Background:Triple‐negative breast cancer(TNBC)displays high heterogeneity.The majority of TNBC cases are characterized by high Ki‐67 expression.TNBC with low Ki‐67 expression accounts for only a small fraction of cases and has been relatively less studied.Methods:This study analyzed a large single‐center multiomics TNBC data set,combined with a single‐cell data set.The clinical,genomic,and metabolic characteristics of patients with low Ki‐67 TNBC were analyzed.Results:The clinical and pathological characteristics were analyzed in 2217 TNBC patients.Low Ki‐67 TNBC was associated with a higher patient age at diagnosis,a lower proportion of invasive ductal carcinoma,increased alterations in the PI3K‐AKT‐mTOR pathway,upregulated lipid metabolism pathways,and enhanced infiltration of M2 macrophages.High Ki‐67 TNBC exhibited a higher prevalence of TP53 gene mutations,elevated nucleotide metabolism,and increased infiltration of M1 macrophages.Conclusions:We identified specific genomic and metabolic characteristics unique to low Ki‐67 TNBC,which have implications for the development of precision therapies and patient stratification strategies.展开更多
Triple-negative breast cancer(TNBC)remains the most aggressive cluster of all breast cancers,which is due to its rapid progression,high probabilities of early recurrence,and distant metastasis resistant to standard tr...Triple-negative breast cancer(TNBC)remains the most aggressive cluster of all breast cancers,which is due to its rapid progression,high probabilities of early recurrence,and distant metastasis resistant to standard treatment.Following the advances in cancer genomics and transcriptomics that can illustrate the comprehensive profiling of this heterogeneous disease,it is now possible to identify different subclasses of TNBC according to both intrinsic signals and extrinsic microenvironment,which have a huge influence on predicting response to established therapies and picking up novel therapeutic targets for each cluster.In this review,we summarize basic characteristics and critical subtyping systems of TNBC,and particularly discuss newly found prospective targets and relevant medications,which were proved promising in clinical trials,thus shedding light on the future development of precision treatment strategies.展开更多
Background Immune checkpoint inhibitors(ICIs)shed new light on triple-negative breast cancer(TNBC),but only a minority of patients demonstrate response.Therefore,adaptive immune resistance(AIR)needs to be further defi...Background Immune checkpoint inhibitors(ICIs)shed new light on triple-negative breast cancer(TNBC),but only a minority of patients demonstrate response.Therefore,adaptive immune resistance(AIR)needs to be further defined to guide the development of ICI regimens.Methods Databases,including The Cancer Genome Atlas,Gene Ontology Resource,University of California Santa Cruz Genome Browser,and Pubmed,were used to screen epigenetic modulators,regulators for CD8+T cells,and transcriptional regulators of programmed cell death-ligand 1(PD-L1).Human peripheral blood mononuclear cell(Hu-PBMC)reconstruction mice were adopted for xenograft transplantation.Tumor specimens from a TNBC cohort and the clinical trial CTR20191353 were retrospectively analyzed.RNA-sequencing,Western blotting,qPCR and immunohistochemistry were used to assess gene expression.Coculture assays were performed to evaluate the regulation of TNBC cells on T cells.Chromatin immunoprecipitation and transposase-accessible chromatin sequencing were used to determine chromatin-binding and accessibility.Results The epigenetic modulator AT-rich interaction domain 1A(ARID1A)gene demonstrated the highest expression association with AIR relative to other epigenetic modulators in TNBC patients.Low ARID1A expression in TNBC,causing an immunosuppressive microenvironment,promoted AIR and inhibited CD8+T cell infiltration and activity through upregulating PD-L1.However,ARID1A did not directly regulate PD-L1 expression.We found that ARID1A directly bound the promoter of nucleophosmin 1(NPM1)and that low ARID1A expression increased NPM1 chromatin accessibility as well as gene expression,further activating PD-L1 transcription.In Hu-PBMC mice,atezolizumab demonstrated the potential to reverse ARID1A deficiency-induced AIR in TNBC by reducing tumor malignancy and activating anti-tumor immunity.In CTR20191353,ARID1A-low patients derived more benefit from pucotenlimab compared to ARID1A-high patients.Conclusions In AIR epigenetics,low ARID1A expression in TNBC contributed to AIR via the ARID1A/NPM1/PD-L1 axis,leading to poor outcome but sensitivity to ICI treatment.展开更多
Dear Editor,Since the discovery of short hairpin RNA(shRNA)vec-tor-mediated RNA interference(RNAi),this technology has been widely used in cancer research for its specific-ity,potency,and convenience.However,researche...Dear Editor,Since the discovery of short hairpin RNA(shRNA)vec-tor-mediated RNA interference(RNAi),this technology has been widely used in cancer research for its specific-ity,potency,and convenience.However,researchers may find it costly to purchase commercial vectors from bio-companies or time-and labor-consuming to construct their own shRNA vectors using traditional method by inserting annealed duplex into digested vectors.Despite intensive efforts to accelerate shRNA vector cloning in laboratories,the development of a reliable,rapid,conven-ient,and cost-effective method is still in great demand.To this end,we developed a novel method named SuperSH(Super rapid cloning of shRNA vector)for the effective and rapid construction of shRNA-expressing vectors based on high-performance DNA polymerase and seamless cloning technique[1](Additional file 1:Fig-ure S1a;the detailed methods can be found in Additional file 1).In our SuperSH method,the shRNA sequences are introduced into the vector via a pair of polymerase chain reaction(PCR)primers rather than via annealed duplex.In detail,the 3′ends of the primers are designed to bind the template to initiate a PCR to amplify the vector back-bone,and the 5′portions are designed to introduce the sequences of interest as well as to form a short homol-ogous arm for subsequent recombination via seamless cloning[1].展开更多
Purpose:Breast cancer is now the most common malignant tumor worldwide.About one-fourth of female cancer patients all over the world sufer from breast cancer.And about one in six female cancer deaths worldwide is caus...Purpose:Breast cancer is now the most common malignant tumor worldwide.About one-fourth of female cancer patients all over the world sufer from breast cancer.And about one in six female cancer deaths worldwide is caused by breast cancer.In terms of absolute numbers of cases and deaths,China ranks frst in the world.The CACA Guidelines for Holistic Integrative Management of Breast Cancer were edited to help improve the diagnosis and comprehensive treatment in China.Methods:The Grading of Recommendations Assessment,Development and Evaluation(GRADE)was used to classify evidence and consensus.Results:The CACA Guidelines for Holistic Integrative Management of Breast Cancer include the epidemiology of breast cancer,breast cancer screening,breast cancer diagnosis,early breast cancer treatment,advanced breast cancer treatment,follow-up,rehabilitation,and traditional Chinese medicine treatment of breast cancer patients.Conclusion:We to standardize the diagnosis and treatment of breast cancer in China through the formulation of the CACA Guidelines.展开更多
基金supported by the National Key Research and Development Program of China(No.2020YFA0112304)the National Natural Science Foundation of China(No.82373167,82341003 and 92159301)+3 种基金the Natural Science Foundation of Shanghai(No.22ZR1479200)the Shanghai Key Laboratory of Breast Cancer(No.12DZ2260100)the SHDC Municipal Project for Developing Emerging and Frontier Technology in Shanghai Hospitals(No.SHDC12021103)Shanghai Medical Innovation Research Project(No.22Y11912700),and Shanghai Anticancer Association EYAS PROJECT(No.SACA-CY22A05).
文摘Objective:Recurrence continues to be a pivotal challenge among hormone receptor-positive(HR^(+))/human epidermal growth factor receptor 2^(−)negative(HER2^(−))breast cancers.In the international consensus guidelines,HR^(+)/HER2^(−)breast cancer relapse patterns are divided into three distinct types:primary resistant,secondary resistant,and endocrine sensitive.However,owing to the lack of cohorts with treatment and follow-up data,the heterogeneity among different recurrence patterns remains uncharted.Current treatments still lack precision.Methods:This analysis included data from a large-scale multiomics study of a HR^(+)/HER2^(−)breast cancer cohort(n=314).Through the analysis of transcriptomics(n=312),proteomics(n=124),whole-exome sequencing(n=290),metabolomics(n=217),and digital pathology(n=228)data,we explored distinctive molecular features and identified putative therapeutic targets for patients experiencing recurrence.Results:We explored distinct clinicopathological characteristics,biological heterogeneity,and potential therapeutic strategies for recurrence.Based on a shared relapse signature,we stratified patients into high-and lowrecurrence-risk groups.Patients with different relapse patterns presented unique molecular features in primary tumors.Specifically,receptor tyrosine kinase(RTK)pathway activation in the primary resistant group suggested the utility of RTK inhibitors,whereas mammalian target of rapamycin(mTOR)and cell cycle pathway activation in the secondary resistant group highlighted the potential of mTOR and CDK4/6 inhibitors.Interestingly,the endocrine-sensitive group displayed a quiescent state and high genomic instability,suggesting that targeting quiescent cells and using poly-ADP-ribose polymerase(PARP)inhibitors could be effective strategies.Conclusions:These findings illuminate the clinicopathological and molecular landscape of HR^(+)/HER2^(−)breast cancer patients with distinct recurrence patterns,highlighting potential targeted therapies.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant No.82103039)the Program of Shanghai Academic/Technology Research Leader(Grant No.20XD1421100)the Wu Jieping Medical Foundation(Grant No.320.6750.2021-10-64).
文摘Objective:Triple-negative breast cancer(TNBC)is a heterogeneous and aggressive cancer.Although our previous study classified primary TNBC into four subtypes,comprehensive longitudinal investigations are lacking.Methods:We assembled a large-scale,real-world cohort comprised of 880 TNBC patients[465 early-stage TNBC(eTNBC)and 415 metastatic TNBC(mTNBC)patients]who were treated at Fudan University Shanghai Cancer Center.The longitudinal dynamics of TNBC subtypes during disease progression were elucidated in this patient cohort.Comprehensive analysis was performed to compare primary and metastatic lesions within specific TNBC subtypes.Results:The recurrence and metastasis rates within 3 years after initial diagnosis in the eTNBC cohort were 10.1%(47/465).The median overall survival(OS)in the mTNBC cohort was 27.2 months[95%confidence interval(CI),24.4–30.2 months],which indicated a poor prognosis.The prognostic significance of the original molecular subtypes in both eTNBC and mTNBC patients was confirmed.Consistent molecular subtypes were maintained in 77.5%of the patients throughout disease progression with the mesenchymal-like(MES)subtype demonstrating a tendency for subtype transition and brain metastasis.Additionally,a precision treatment strategy based on the metastatic MES subtype of target lesions resulted in improved progression-free survival in the FUTURE trial.Conclusions:Our longitudinal study comprehensively revealed the clinical characteristics and survival of patients with the original TNBC subtypes and validated the consistency of most molecular subtypes throughout disease progression.However,we emphasize the major importance of repeat pathologic confirmation of the MES subtype.
基金supported by the National Key Research and Development Program of China(2023YFC2506400,2020YFA0112300)National Natural Science Foundation of China(82230103,81930075,82073267,82203399,82372689)+1 种基金Program for Outstanding Leading Talents in ShanghaiInnovative Research Team of High-level Local University in Shanghai。
文摘Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and differentiation.Studies have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast cancer.The tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ability.Hence,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer metastasis.In this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory mechanisms.Furthermore,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during metastasis.Overall,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.
基金supported by grants from the National Key Research and Development Project of China(Grant No.2020YFA0112304)the National Natural Science Foundation of China(Grant Nos.81922048,82072922,91959207,and 92159301)+3 种基金the Program of Shanghai Academic/Technology Research Leader(Grant No.20XD1421100)the Shanghai Key Laboratory of Breast Cancer(Grant No.12DZ2260100)the Clinical Research Plan of SHDC(Grant Nos.SHDC2020CR4002 and SHDC2020CR5005)the SHDC Municipal Project for Developing Emerging and Frontier Technology in Shanghai Hospitals(Grant No.SHDC12021103).
文摘Objective:Mammographic calcifications are a common feature of breast cancer,but their molecular characteristics and treatment implications in hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-negative(HER2−)breast cancer remain unclear.Methods:We retrospectively collected mammography records of an HR+/HER2−breast cancer cohort(n=316)with matched clinicopathological,genomic,transcriptomic,and metabolomic data.On the basis of mammographic images,we grouped tumors by calcification status into calcification-negative tumors,tumors with probably benign calcifications,tumors with calcification of lowmoderate suspicion for maligancy and tumors with calcification of high suspicion for maligancy.We then explored the molecular characteristics associated with each calcification status across multiple dimensions.Results:Among the different statuses,tumors with probably benign calcifications exhibited elevated hormone receptor immunohistochemical staining scores,estrogen receptor(ER)pathway activation,lipid metabolism,and sensitivity to endocrine therapy.Tumors with calcifications of high suspicion for malignancy had relatively larger tumor sizes,elevated lymph node metastasis incidence,Ki-67 staining scores,genomic instability,cell cycle pathway activation,and may benefit from cyclin-dependent kinase 4 and 6(CDK4/6)inhibitors.Conclusions:Our research established links between tumor calcifications and molecular features,thus proposing potential precision treatment strategies for HR+/HER2−breast cancer.
基金supported by the Ministry of Education Innovation Team(Grant No.IRT1223)and the Shanghai Health System Joint Project of Key Disease(Grant No.2013ZYJB0302).
文摘Objective:Sentinel lymph node biopsy(SLNB)is currently the standard of care in clinically node negative(cN0)breast cancer.The present study aimed to evaluate the negative predictive value(NPV)of 18F-FDG dedicated lymph node positron emission tomography(LymphPET)in cN0 patients.Methods:This was a prospective phase II trial divided into 2 stages(NCT04072653).In the first stage,cN0 patients underwent axillary LymphPET followed by SLNB.In the second stage,SLNB was omitted in patients with a negative preoperative axillary assessment after integration of LymphPET.Here,we report the results of the first stage.The primary outcome was the NPV of LymphPET to detect macrometastasis of lymph nodes(LN-macro).Results:A total of 189 patients with invasive breast cancer underwent LymphPET followed by surgery with definitive pathological reports.Forty patients had LN-macro,and 16 patients had only lymph node micrometastasis.Of the 131 patients with a negative LymphPET result,16 patients had LN-macro,and the NPV was 87.8%.After combined axillary imaging evaluation with ultrasound and LymphPET,100 patients were found to be both LymphPET and ultrasound negative,9 patients had LN-macro,and the NPV was 91%.Conclusions:LymphPET can be used to screen patients to potentially avoid SLNB,with an NPV>90%.The second stage of the SOAPET trial is ongoing to confirm the safety of omission of SLNB according to preoperational axillary evaluation integrating LymphPET.
文摘Objective:This study aimed to assess the efficacy and safety of various neoadjuvant regimens for patients diagnosed with early-stage or locally advanced triple-negative breast cancer(TNBC).Methods:Medline,EMBASE,Cochrane Library,and Web of Science were searched in May 2020 to identify randomized controlled trials(RCTs).Bayesian network meta-analysis(NMA)was performed(Registration:PROSPERO CRD42020223012).Results:A total of 35 RCTs involving 8,424 participants were reviewed,of which 22 RCTs with 5,203 patients were included in this NMA focusing on pathologic complete response(pCR).An anthracycline-taxane-based(AT)regimen combined with a platinum(ATPt)[odds ratio(OR)=2.04,95%credible interval(CrI):1.69,2.48]regimen,and a docetaxel regimen combined with a carboplatin(TCb;OR=2.16,95%CrI:1.20,3.91)regimen improved pCR beyond that with AT only.AT and ATPt combined with targeted therapy[including bevacizumab(Bev),veliparib,atezolizumab,or pembrolizumab]also improved pCR.Five RCTs included in this NMA reported serious adverse events(SAEs)or grade≥3 AEs.TCb was associated with fewer grade≥3 AEs than was AT(OR=0.66,95%CrI:0.23,1.72)alone.In contrast,ATPt,AT+Bev,ATPt+Bev,ATPt+veliparib,and ATPt+pembrolizumab were associated with more SAEs than was AT alone.Conclusions:In patients with TNBC,platinum-based neoadjuvant regimens ATPt and TCb increase pCR beyond that with AT alone,but TCb appears to be better tolerated than either AT or ATPt.Platinum-based regimens combined with targeted therapies(Bev,PARPi,and PD-1/PD-L1 inhibitor)also improve the pCR rate beyond that with AT alone,but this benefit is accompanied by greater toxicity.
文摘The concept of antibody±drug conjugations(ADCs)can be tracked back to the early 20^(th) century when the renowned immunologist,Paul Ehrlich,proposed the idea of a"magic bullet",which utilizes ADCs for targeted destruction of microorganisms and tumor cells^(1).After nearly one century of development,ADCs have emerged as a rather promising approach in the treatment of cancer,especially breast cancer,which is the most common malignant tumor in women^(2).
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.91959207 and 92159301)。
文摘Ferroptosis,a type of regulated cell death named one decade ago,is a unique type driven by lipid peroxidation in an iron-dependent manner.Ferroptosis differs radically from apoptosis and other regulated forms of cell death in both morphology and molecular underpinning.Ferroptosis can be triggered by a variety of physiologic conditions and pathologic stresses.There has been growing interest in ferroptosis in recent years,and research on ferroptosis is productive.
基金This work was supported by Grants from the National Key R&D Project of China(Grant No.2020YFA0112304)the National Natural Science Foundation of China(Grant Nos.91959207,92159301 and 82002792)+3 种基金the Shanghai Key Laboratory of Breast Cancer(Grant No.12DZ2260100)the Shanghai Key Clinical Specialty of Oncology(Grant No.shslczdzk02001)the Clinical Research Plan of SHDC(Grant Nos.SHDC2020CR4002 and SHDC2020CR5005)the Shanghai Sailing Program(Grant No.20YF1408600).
文摘Breast cancer is the most common malignant tumor in Chinese women,and its incidence is increasing.Regular screening is an effective method for early tumor detection and improving patient prognosis.In this review,we analyze the epidemiological changes and risk factors associated with breast cancer in China and describe the establishment of a screening strategy suitable for Chinese women.Chinese patients with breast cancer tend to be younger than Western patients and to have denser breasts.Therefore,the age of initial screening in Chinese women should be earlier,and the importance of screening with a combination of ultrasound and mammography is stressed.Moreover,Chinese patients with breast cancers have several ancestry-specific genetic features,and aiding in the determination of genetic screening strategies for identifying high-risk populations.On the basis of current studies,we summarize the development of risk-stratified breast cancer screening guidelines for Chinese women and describe the significant improvement in the prognosis of patients with breast cancer in China.
基金the Li lab is supported by the National Natural Science Foundation of China(Nos.81372847 and 81572584)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(No.2013-06)+1 种基金the Innovation Program of Shanghai Municipal Education Commission(No.2015ZZ007)the New Investigator Start-up Fund from Fudan University
文摘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.
基金supported by National Natural Science Foundation of China grants(Nos.81530075 and 81472741)the National Key Research and Development Program of China(Stem Cell and Translational Research 2016YFA0101202)the Ministry of Science and Technology(MOST) grant (No.2015CB553800)
文摘Breast cancer susceptibility gene 1(BRCA1)is a tumor suppressor gene,and its protein BRCA1 plays a role in DNA repair[1].BRCA1 is generally expressed in the cells of mammary glands and other tissues,helping to repair damaged DNA or disrupting cells when DNA cannot be repaired.When BRCA1 is mutated and cannot function and therefore the damaged DNA cannot be repaired
基金This work was supported by grants from the National Natural Science Foundation of China(Grant Nos.81874053,82072879,and 82173022).
文摘The RNA component of mitochondrial RNA-processing endoribonuclease(RMRP)was first described as an entity that cleaved mitochondrial RNA at a priming site of mitochondrial DNA replication.This long noncoding RNA(lncRNA)was encoded by an evolutionarily conserved nuclear gene that has been characterized in many species,including human,mouse,cattle,zebrafish,toad,and yeast.It was soon learned that RMRP as a component of the RNase MRP complex was also located in the nucleus,and was critical for ribosomal RNA(rRNA)processing,particularly the biosynthesis of 5.8S rRNAs.In 2001,the first evidence of the role of RMRP in the pathogenesis of human disorders was reported,involving mutations in the RMRP gene,which caused cartilage-hair hypoplasia(CHH)1,a recessively inherited developmental disorder characterized by short stature,hypoplastic anemia,defective immunity,and predisposition to several cancers.
基金This work was supported by the National Key R&D Program of China(Grant Nos.2020YFA0803402 and 2019YFA0801703)the Natural Science Foundation of China(Grant Nos.81790250/81790253,91959202,82121004,and 81872240)the Innovation Program of Shanghai Municipal Education Commission(Grant No.N173606).
文摘Metabolic remodeling is a key feature of cancer development.Knowledge of cancer metabolism has greatly expanded since the first observation of abnormal metabolism in cancer cells,the so-called Warburg effect.Malignant cells tend to modify cellular metabolism to favor specialized fermentation over the aerobic respiration usually used by most normal cells.Thus,targeted cancer therapies based on reprogramming nutrient or metabolite metabolism have received substantial attention both conceptually and in clinical practice.In particular,the management of nutrient availability is becoming more attractive in cancer treatment.In this review,we discuss recent findings on tumor metabolism and potential dietary interventions based on the specific characteristics of tumor metabolism.First,we present a comprehensive overview of changes in macronutrient metabolism.Carbohydrates,amino acids,and lipids,are rewired in the cancer microenvironment individually or systematically.Second,we summarize recent progress in cancer interventions applying different types of diets and specific nutrient restrictions in pre-clinical research or clinical trials.
文摘Breast cancer metastasis remains the leading cause of mortality in patients,yet its mechanisms are poorly understood.A recent Cell paper highlights the pivotal role of the proprotein convertase subtilisin/kexin type 9(PCSK9)V474I germline variant in driving metastatic progression through suppression of the low-density lipoprotein receptor-related protein 1(LRP1)receptor,revealing novel therapeutic opportunities and genetic insights.
基金supported by grants from the National Key Research and Development Program of China(2021YFF1201300 and 2021YFF1201305)the National Natural Science Foundation of China(82103039,81572583,81922048,91959207,U1809205,92159301,61771249 and 62171230)。
文摘Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype.Molecular stratification and target therapy bring clinical benefit for TNBC patients,but it is difficult to implement comprehensive molecular testing in clinical practice.Here,using our multi-omics TNBC cohort(N=425),a deep learning-based framework was devised and validated for comprehensive predictions of molecular features,subtypes and prognosis from pathological whole slide images.The framework first incorporated a neural network to decompose the tissue on WSIs,followed by a second one which was trained based on certain tissue types for predicting different targets.Multi-omics molecular features were analyzed including somatic mutations,copy number alterations,germline mutations,biological pathway activities,metabolomics features and immunotherapy biomarkers.It was shown that the molecular features with therapeutic implications can be predicted including the somatic PIK3CA mutation,germline BRCA2 mutation and PD-L1 protein expression(area under the curve[AUC]:0.78,0.79 and 0.74 respectively).The molecular subtypes of TNBC can be identified(AUC:0.84,0.85,0.93 and 0.73 for the basal-like immune-suppressed,immunomodulatory,luminal androgen receptor,and mesenchymal-like subtypes respectively)and their distinctive morphological patterns were revealed,which provided novel insights into the heterogeneity of TNBC.A neural network integrating image features and clinical covariates stratified patients into groups with different survival outcomes(log-rank P<0.001).Our prediction framework and neural network models were externally validated on the TNBC cases from TCGA(N=143)and appeared robust to the changes in patient population.For potential clinical translation,we built a novel online platform,where we modularized and deployed our framework along with the validated models.It can realize real-time one-stop prediction for new cases.In summary,using only pathological WSIs,our proposed framework can enable comprehensive stratifications of TNBC patients and provide valuable information for therapeutic decision-making.It had the potential to be clinically implemented and promote the personalized management of TNBC.
基金National Natural Science Foundation of China,Grant/Award Numbers:81872137,82072917,82272957Shanghai Science and Technology Innovation Action Plan,Grant/Award Number:22DZ2204400。
文摘Background:Triple‐negative breast cancer(TNBC)displays high heterogeneity.The majority of TNBC cases are characterized by high Ki‐67 expression.TNBC with low Ki‐67 expression accounts for only a small fraction of cases and has been relatively less studied.Methods:This study analyzed a large single‐center multiomics TNBC data set,combined with a single‐cell data set.The clinical,genomic,and metabolic characteristics of patients with low Ki‐67 TNBC were analyzed.Results:The clinical and pathological characteristics were analyzed in 2217 TNBC patients.Low Ki‐67 TNBC was associated with a higher patient age at diagnosis,a lower proportion of invasive ductal carcinoma,increased alterations in the PI3K‐AKT‐mTOR pathway,upregulated lipid metabolism pathways,and enhanced infiltration of M2 macrophages.High Ki‐67 TNBC exhibited a higher prevalence of TP53 gene mutations,elevated nucleotide metabolism,and increased infiltration of M1 macrophages.Conclusions:We identified specific genomic and metabolic characteristics unique to low Ki‐67 TNBC,which have implications for the development of precision therapies and patient stratification strategies.
基金the National Natural Science Foundation of China(81922048,81874112,81874113,81572583,and 81502278)the Fok Ying-Tong Education Foundation for College Young Teachers(171034)+4 种基金the Training Plan of Excellent Talents in Shanghai Municipality Health System(2017YQ038)the“Chen Guang”project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation(17CG01)Shanghai Pujiang Program(18PJD007)the Training Plan of Excellent Talents of Fudan University Shanghai Cancer Center(YJYQ201602)The funders had no role in the study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘Triple-negative breast cancer(TNBC)remains the most aggressive cluster of all breast cancers,which is due to its rapid progression,high probabilities of early recurrence,and distant metastasis resistant to standard treatment.Following the advances in cancer genomics and transcriptomics that can illustrate the comprehensive profiling of this heterogeneous disease,it is now possible to identify different subclasses of TNBC according to both intrinsic signals and extrinsic microenvironment,which have a huge influence on predicting response to established therapies and picking up novel therapeutic targets for each cluster.In this review,we summarize basic characteristics and critical subtyping systems of TNBC,and particularly discuss newly found prospective targets and relevant medications,which were proved promising in clinical trials,thus shedding light on the future development of precision treatment strategies.
基金National Science and Technology Major Project.Grant Number:2020ZX09201-013。
文摘Background Immune checkpoint inhibitors(ICIs)shed new light on triple-negative breast cancer(TNBC),but only a minority of patients demonstrate response.Therefore,adaptive immune resistance(AIR)needs to be further defined to guide the development of ICI regimens.Methods Databases,including The Cancer Genome Atlas,Gene Ontology Resource,University of California Santa Cruz Genome Browser,and Pubmed,were used to screen epigenetic modulators,regulators for CD8+T cells,and transcriptional regulators of programmed cell death-ligand 1(PD-L1).Human peripheral blood mononuclear cell(Hu-PBMC)reconstruction mice were adopted for xenograft transplantation.Tumor specimens from a TNBC cohort and the clinical trial CTR20191353 were retrospectively analyzed.RNA-sequencing,Western blotting,qPCR and immunohistochemistry were used to assess gene expression.Coculture assays were performed to evaluate the regulation of TNBC cells on T cells.Chromatin immunoprecipitation and transposase-accessible chromatin sequencing were used to determine chromatin-binding and accessibility.Results The epigenetic modulator AT-rich interaction domain 1A(ARID1A)gene demonstrated the highest expression association with AIR relative to other epigenetic modulators in TNBC patients.Low ARID1A expression in TNBC,causing an immunosuppressive microenvironment,promoted AIR and inhibited CD8+T cell infiltration and activity through upregulating PD-L1.However,ARID1A did not directly regulate PD-L1 expression.We found that ARID1A directly bound the promoter of nucleophosmin 1(NPM1)and that low ARID1A expression increased NPM1 chromatin accessibility as well as gene expression,further activating PD-L1 transcription.In Hu-PBMC mice,atezolizumab demonstrated the potential to reverse ARID1A deficiency-induced AIR in TNBC by reducing tumor malignancy and activating anti-tumor immunity.In CTR20191353,ARID1A-low patients derived more benefit from pucotenlimab compared to ARID1A-high patients.Conclusions In AIR epigenetics,low ARID1A expression in TNBC contributed to AIR via the ARID1A/NPM1/PD-L1 axis,leading to poor outcome but sensitivity to ICI treatment.
基金by the National Key Research and Development Program of China(Stem Cell and Translational Research 2016YFA0101202)National Nature Science Foundation of China Grants(81530075 and 81472741)+2 种基金Fudan University Research Foundation(IDH 1340042)Research Foundation of the Fudan University Shanghai Cancer Center(YJRC1603)the Ministry of Science and Technology of China Grant(2015CB553800).
文摘Dear Editor,Since the discovery of short hairpin RNA(shRNA)vec-tor-mediated RNA interference(RNAi),this technology has been widely used in cancer research for its specific-ity,potency,and convenience.However,researchers may find it costly to purchase commercial vectors from bio-companies or time-and labor-consuming to construct their own shRNA vectors using traditional method by inserting annealed duplex into digested vectors.Despite intensive efforts to accelerate shRNA vector cloning in laboratories,the development of a reliable,rapid,conven-ient,and cost-effective method is still in great demand.To this end,we developed a novel method named SuperSH(Super rapid cloning of shRNA vector)for the effective and rapid construction of shRNA-expressing vectors based on high-performance DNA polymerase and seamless cloning technique[1](Additional file 1:Fig-ure S1a;the detailed methods can be found in Additional file 1).In our SuperSH method,the shRNA sequences are introduced into the vector via a pair of polymerase chain reaction(PCR)primers rather than via annealed duplex.In detail,the 3′ends of the primers are designed to bind the template to initiate a PCR to amplify the vector back-bone,and the 5′portions are designed to introduce the sequences of interest as well as to form a short homol-ogous arm for subsequent recombination via seamless cloning[1].
基金Department of Breast Surgery,Harbin Medical University Cancer Hospital,Harbin,China。
文摘Purpose:Breast cancer is now the most common malignant tumor worldwide.About one-fourth of female cancer patients all over the world sufer from breast cancer.And about one in six female cancer deaths worldwide is caused by breast cancer.In terms of absolute numbers of cases and deaths,China ranks frst in the world.The CACA Guidelines for Holistic Integrative Management of Breast Cancer were edited to help improve the diagnosis and comprehensive treatment in China.Methods:The Grading of Recommendations Assessment,Development and Evaluation(GRADE)was used to classify evidence and consensus.Results:The CACA Guidelines for Holistic Integrative Management of Breast Cancer include the epidemiology of breast cancer,breast cancer screening,breast cancer diagnosis,early breast cancer treatment,advanced breast cancer treatment,follow-up,rehabilitation,and traditional Chinese medicine treatment of breast cancer patients.Conclusion:We to standardize the diagnosis and treatment of breast cancer in China through the formulation of the CACA Guidelines.
