Chinese Society of Clinical Oncology Breast Cancer(CSCO BC)Guidelines in 2024:International Contributions from China

The Chinese Society of Clinical Oncology Breast Cancer(CSCO BC)guidelines have been widely implemented in China since the first release in 2017.The Guideline Working Committee has also published multiple versions in English,Arabic,and other languages to facilitate communications with international experts.

New generation of breast cancer clinical trials implementing molecular profiling

The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as prescreening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i)longitudinal cohort studies that implement(or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials.

Breast Cancer: Epidemiological, Clinical, and Therapeutic Aspects in Pointe Noire (Congo Brazzaville)

Introduction: Breast cancer is the leading cancer and the leading cause of cancer death in women worldwide. The objective of our study was to describe the epidemiological, clinical and therapeutic aspects of breast cancer at the General Hospital of Loandjili in Pointe Noire. Patients and Methods: This was a descriptive and cross-sectional study that took place in the Cancer Department of the General Hospital of Loandjili in Pointe Noire during the period from January 1st, 2012 to December 31st, 2016 for duration of 5 years. 54 records of patients over 18 years of age with histological evidence were collected. The variables studied were: age, level of education, time to presentation, telltale sign, stage of extension, histological type, and histological grade. Chi-square test was used to compare variables and groups. Results: At the end of this study, we collected 54 files of breast cancer patients from 150 patients hospitalized in the Cancer Department. The frequency of breast cancer was 36%. The average age was 50 ± 13.6 years;the extremes were 27 years and 79 years. The most represented age group was from 37 to 40 years old with a percentage of 28%. The patient’s level of study was primary in the majority of cases (57%). The most represented histological type was invasive ductal carcinoma, (100%). The majority of patients arrived at advanced stages 44.4% and metastatic stages 26%. Patients were treated in most of cases by chemotherapy (82%), surgery (42%) and radiotherapy (10%). There was a correlation between time of presentation and stage of extension. Conclusion: Breast cancer is the first cancer of the woman in Pointe Noire. Patients arrive at advanced stages;the most common histological type is invasive ductal carcinoma. The presentation time is correlated with the extension stage. These results suggest the establishment of a cancer control program in developing countries.

Epidemiological and Clinical Profile of Breast Cancer at Bamako Radiotherapy Center

Breast cancer is a major public health problem because of its incidence and mortality. Purpose: To establish the epidemiological and clinical characteristics of breast cancer seen at the radiotherapy center at the Mali Hospital of Bamako. Patients and methods: It was a retrospective, descriptive study of data from patients seen for breast cancer at the Center of Radiotherapy of Mali Hospital between April 2014 and December 2016. The parameters studied were: age, sex, family history of breast cancer, menopausal status, parity, breast tumor location, histological type, histological grade, cancer classification stage. Results: 134 cases of breast cancer were collected, with a frequency of 15%. The sex ratio (H/F) of 0.007. The patient’s mean age was 47 ± 11 years old. The most represented age groups were 33 - 47 years old with 45.5% and 48 - 62 years old with 39%. Three percent (3%) of patients had a family history of breast cancer. Fifty (50%) of the patients were menopausal. The main clinical signs found were : mammary nodules (98%), mastodynia (65%), nodes (67%). Invasive ductal carcinomas were found in 94% of patients, followed by infiltrating lobular carcinomas with 3.7% and metaplastic carcinomas with 1.7%. SBR Grades II and III were mostly found with 37% and 23%. The average tumor size was 87 mm ± 43. Stage III was predominantly represented with 72%, followed by Stage II with 24% and Stages I and IV with 2% each. Conclusion: Breast cancer is common and reaches both before and after 50 years;the diagnosis is usually late;hence it is the importance of raising awareness and screening before the age of 50 and popularizing some complementary tests to better understand the prognosis of this disease and promote more targeted and conservative treatments that will improve survival.

The Value of Clinical Breast Examination, Imaging, and Fine Needle Aspiration and the Challenge of Diagnosing Breast Cancer in a Low Resource Setting: A Hospital-Based Analytical Study in Yaounde

Background: Breast cancer is the most common cancer in the world, as well as in Cameroon, where it represents about 20.1% of all cancers recorded in 2020. The number of pathologists in the country is as few as seven for a population of about 26 million. The diagnostic performances of diagnostic modalities other than histology—clinical breast examination (CBE), imaging and fine needle aspiration and cytology (FNA)—in our context are not known. Study Objectives: Our objectives were to estimate the proportions of cases managed with mammography, breast ultrasound and FNA and to estimate the sensitivity, specificity, positive and negative predictive values, and accuracy of CBE, mammography, breast ultrasound and FNA;using histology as reference. Study Methodology: The study was cross-sectional and analytical, and was carried out at the Yaoundé General Hospital. It lasted twelve months, April 2015 through March 2016 and covered the period January 2010 to February 2016. Using histology as reference, we calculated measures of diagnostic accuracy for all four modalities using the statistical methods of Galen and Gambino. Results: We recruited 107 cases, 105 females (98.1%) and 02 males. We had 112 breast lumps, 106 malignant (94.6%) and 6 benign. The mean lump size was 61.1 mm. The most frequently used diagnostic tool after CBE was FNA (49.1%), while the diagnostic accuracies were 76.8%, 79.1%, 82.9%, and 82.0% for CBE, breast US, mammography and FNA. Conclusion: The four baseline diagnostic modalities for breast cancer are used sub-optimally and FNA appears to be the most commonly used in our setting after CBE. We recommend that FNA should be considered for diagnosis as appropriate but a negative result should not stop the quest for histological elimination of presence of malignancy.

Epidemiological Clinical and Histological Aspects of Gynecological and Breast Cancer in Pointe Noire (Congo Brazzaville)

INTRODUCTION: The objective of our study was to determine the epidemiological clinical and histological aspects of gynecological and breast cancers in Pointe-Noire. PATIENTS AND METHODS: This was a retrospective descriptive study that took place in the cancerology and internal medicine department during the period from January 1, 2012 to December 31, 2021, i.e. a period of 10 years. Women with histological diagnosis of gynecological and breast cancers were included in our study. The variables studied were: frequency, age, alcohol and tobacco consumption, histological type, stage of extension, location of cancer. Bivariate analysis was done between age and location of the tumour. The statistical test used was the KHI2 test. The results were statistically significant for a value of p RESULTS: We collected 400 files from women with cancer. Among the 400 files, 265 were represented by gynecological and breast cancers, that is a frequency of 65.43%. Among the 265 cases of gynecological and breast cancer identified during this study period, breast cancer represented the first rank with 52% frequency. Cervical cancer accounted for 41% followed by ovarian cancer (5%) and endometrial (2%). Cancer of vulva was represented by a single case. The average age of patients with gynecological and breast cancers during our study was 52 ± 12 years. The average age of patients with cancer of the breast, cervix, ovarian, endometrial was respectively 49 ± 11.97 years, 54.73 ± 12.91 years old, 50 ± 14 years, 67 ± 14.24 years, the age of the vulva cancer patient was 51 years old. The histological type of breast cancer was represented by infiltrating ductal adenocarcinoma in 91% of cases, invasive lobular carcinoma in 7% and sarcoma in 2%. Cervical cancers were represented by squamous cell carcinomas in 95% of cases and adenocarcinomas in 5% of cases. Vulva cancer was represented by squamous cell carcinoma, ovarian cancer was represented by epithelial tumors (adenocarcinoma) in 100% of cases. Endometrial cancers were represented by endometrial adenocarcinoma. All cancers were diagnosed at advanced stages (locoregional and metastatic stage). Patients over the age of 50 had more gynecological and breast cancers;but this result was not significant. CONCLUSION: Gynecological and breast cancers are frequent and constitute the first cancer of Congolese women in Pointe-Noire. Breast cancer is the first cancer followed by cancer of the cervix and ovaries. The histological types are those of the literature. Patients with gynecological and breast cancers consult at very advanced stages.

Advances in Clinical Application of Postoperative Radiotherapy for Breast Cancer

Objective:To explore the clinical value of color Doppler ultrasonography in the diagnosis of breast cancer.Methods:99 cases of breast cancer patients were selected as the research object,retrospective analysis of its clinical treatment data.Results:The group of 99 patients,97 confirmed cases,2 cases were misdiagnosed,the diagnostic accuracy rate was 97.98%.Conclusion:Color Doppler ultrasonography in patients with breast cancer has the advantages of high accuracy,simple operation and noninvasive.It is worthy of promotion.

The Study on the Clinical Features and Prognosis of Pregnancy-related Breast Cancer

Objective: To explore the clinical features ofpregnancy-related breast cancer and the related factorsaffecting the prognosis. Methods: The research workwas carried out in our hospital from January 2018 toJanuary 2019. In this study, 50 patients were selectedas related breast cancer patients and 50 non-pregnancyrelated breast cancer patients were selected as controlgroup. The clinical characteristics and prognosis ofthe two groups were compared and analyzed. Results:According to the incidence of pregnancy-related breastcancer, the onset of breast cancer is in pregnancy andlactation, with more than half of the total number ofpatients having two or more pregnancies and 74.0%of the patients having breast feeding history. In thetwo groups, most of the patients went to see a doctorbecause of palpable breast masses, and the averagemaximum diameter of tumors in PBC group was (5.13± 3.22)cm, including 5 cases accompanied by dimplesign, 7 cases accompanied by nipple depression, 8cases accompanied by inflammatory changes of skin,3 cases with pathological changes involving wholemilk, and 27 cases (54.00%) with palpable axillaryenlarged lymph nodes on the same side. The averagemaximum value of tumor in Non-PABC group was(3.94 ± 2.11) cm, with 5 cases accompanied by dimplesign, 4 cases accompanied by nipple depression, and 9cases (18.00%) with palpable axillary lymph nodes onthe same side. Conclusion: As far as pregnancy-relatedbreast cancer is concerned, the clinical misdiagnosisrate is relatively high and the prognosis is poor.Prenatal examination and breast-feeding breast cancerexamination are needed to ensure early detection anddiagnosis. This is the key factor to ensure the survivalrate of pregnancy-related breast cancer patients and haspositive significance for clinical development.

Prediction of Nipple and Areola Complex Invasion in Breast Cancer Patients. Clinical and Pathological Study of Surgical Specimens

Breast conservation surgery (BCS) and nipple-areola-sparing (NAS) mastectomy have been recognized as two milestones in this period. This study included 60 Egyptian female patients with breast cancer, all of them were subjected to modified radical mastectomy operation. Methods: This study included female patients > 18 years old who have breast cancer with healthy looking non invaded skin of nipple and areola and excluded patients < 18 years old, patients unfit for surger, patients previously subjected to chemo or radiotherapy for breast cancer. We peformed clinical examination of 60 patients with breast cancer. We studied the relevant factors that affect NAC invasion such as patient’s age, menstrual state, family history, tumor size, tumor location (central vs peripheral), tumor to nipple distance, lymphovascular invasion of NAC, lymph node metastasis, histological tumor type, tumor stage, multifocal/multicentric tumors and (ER, PR, HER2) status. Result: In our study, we have shown that NAC invasion is strongly associated with: 1) Nipple retraction as a patient’s complaint;2) Tumor site;3) Tumor-nipple-distance ≤ 4 cm;4) Multifocal/multicentric tumor;5) Tumor grade (grade III tumors);6) Positive lymph node invasion;7) ER and PR receptors negativity;8) HER2 positivity. This helps in preoperative planning for selecting patients for NAS mastectomy. Conclusion: The ideal patients for NAS mastectomy are with these criteria: 1) Clinically normal nipple areola complex;2) Distance from the tumor to the nipple is >4 cm;3) No multifocal/multicentric tumor;4) Absence of lymph node invasion;5) Tumor grade (grade I, II);6) Peripheral not central tumor;7) No sub-areolar lymphovascular invasion (LVI);8) ER receptor positive;9) PR receptor positive;10) HER2 negative.

The prognostic genes of breast cancer and clinical significance

Breast cancer is one of the most frequent malignant tumors and is receiving more attention due to the increasing incidence and detection rate.Further studies regarding prognosis genes for biology are being conducted.The paper aims to review the prognostic indexes of breast cancer such as p16,Her-2,Ki-67,MCM7.

Assessing the Clinical Efficacy and Effectiveness of Sentinel Lymph Node Biopsy Combined with Breast-Conserving Surgery for Early-Stage Breast Cancer

Objective:To analyze the impact of sentinel lymph node biopsy(SLNB)combined with breast-conserving surgery in the clinical treatment of early-stage breast cancer.Methods:80 patients with early-stage breast cancer admitted to the Second Department of Breast Surgery at Dezhou Second People’s Hospital from September 2020 to September 2022 were selected and randomly divided into a control group and an observation group using the random number table method,with 40 cases in each group.The control group underwent a modified radical mastectomy,while the observation group underwent SLNB combined with breast-conserving surgery.The surgical efficacy and prognosis between the two groups were compared.Results:The observation group exhibited shorter operation,hospitalization,and extubation times,as well as less intraoperative blood loss and drainage volume,all of which were significantly better than those in the control group(P<0.05).Additionally,the observation group demonstrated a higher rate of excellent breast cosmetology and quality of life,with lower complication incidence,significantly outperforming the control group(P<0.05).There was no statistical difference in the metastasis rate and recurrence rate between the two groups(P>0.05).Conclusion:The combination of SLNB and breast-conserving surgery proves highly effective for patients with early-stage breast cancer,presenting fewer complications and enhancing both breast cosmetic outcomes and quality of life.

Proteomics of cell-free breast cancer scaffolds identify clinically relevant imprinted proteins and cancer-progressing properties

The composition of the extracellular tumor microenvironment(TME)has not been fully delineated,limiting the understanding of general cancer-progressing properties within the cancer niche.The interplay and dynamics between cancer cells and the surrounding structures and cells clearly differ between various subtypes of cancer,adding to the complexity of precision medicine[1].

Network pharmacology and experimental validation to reveal the pharmacological mechanisms of Qizhu prescription for treating breast cancer

Objective:To investigate the mechanism underlying the effects exerted by the Qizhu prescription(QZP)in breast cancer(BC),and the respective targets.Methods: Expression data from the ArrayExpress and The Cancer Genome Atlas(TCGA)were used to identify differentially expressed genes(DEGs)in BC.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the DEGs to identify genes involved in protein–protein interactions.Molecular docking was used to explore the dynamic relationship between active molecules and targets.Cell function experiments and animal studies were conducted to evaluate the effects of hub genes and active QZP compounds on BC cell behavior.Results: Among the 25 evaluated BC-related targets of QZP,matrix metalloproteinase-1(MMP1)and epidermal growth factor receptor(EGFR)exhibited the highest degrees of dysregulation.GO and KEGG enrichment analyses revealed that the anti-BC targets of QZP primarily affected drug responses and pathways in cancer cells.Molecular docking analysis suggested potential interactions between EGFR and quercetin/luteolin,as well as between MMP1 and luteolin/kaempferol/quercetin.Quercetin significantly reduced BC cell proliferation,migration,invasion,and tumor development in vivo.Treatment of BC cells with quercetin decreased the expression or activation of several associated proteins.Conclusion: The findings of our study provide new insights into the therapeutic potential of traditional Chinese medicine against BC,with particular reference to QZP.

Overcoming resistance to endocrine therapy in hormone receptorpositive human epidermal growth factor receptor 2-negative(HR^(+)/HER2^(-))advanced breast cancer:a meta-analysis and systemic review of randomized clinical trials

New targeted therapies have been developed to overcome resistance to endocrine therapy(ET)and improve the outcome of HR^(+)/HER2^(-)advanced breast cancer(ABC).We conducted a meta-analysis and systemic review on randomized controlled trials evaluating various targeted therapies in combination with ET in HR^(+)/HER2^(-)ABC.PUBMED and EMBASE databases were searched for eligible trials.Hazard ratios(HRs)for progression-free survival(PFS),odds ratios(ORs)for objective response rate(ORR),clinical benefit rate(CBR),and toxicity were meta-analyzed.Twenty-six studies with data on 10347 patients were included and pooled.The addition of cyclin-dependent kinase 4/6 inhibitors to ET significantly improved median PFS(pooled HR=0.547,P<0.001),overall survival(pooled HR=0.755,P<0.001),and tumor response rates(ORR,pooled OR=1.478,P<0.001;CBR,pooled OR=1.201,P<0.001)with manageable toxicities(pooled OR=3.280,P<0.001).The mammalian targets of rapamycin inhibitors and exemestane were not clinically beneficial for this pooled population including ET-naïve and ET-resistant patients.Moderate improvement in PFS(pooled HR=0.686,P<0.001)yet pronounced toxicities(pooled OR=2.154,P<0.001)were noted in the combination of phosphatidylinositol-4,5-bisphosphate 3-kinase inhibitors with fulvestrant.Future studies are warranted to optimize the population and the dosing sequence of these available options.

HER2-positive circulating tumor cells indicate poor clinical outcome in stageⅠto Ⅲ breast cancer patients

Metastases may occur in node-negative breast cancer patients. It indicates that breast cancer cells can bypass regional lymph nodes and hematogenously disseminate to distant organs. In a recent paper (Clin Cancer Res 2006, 12:1715-1720) , Wulfing et al. evaluated the prognostic value of blood-borne, HER2-positive circulating tumor cells (CTC) in the peripheral blood from 42 breast cancer patients with a median follow-up of 95 months. HER2-

Clinical and pathological features and risk factors for primary breast cancer patients

BACKGROUND Breast cancer is the most common malignancy in women all around the world.According to the latest statistics in 2018,there were more than 2.08 million new breast cancer cases all around the world and more than 620000 deaths;the proportion of breast cancer deaths in women with cancer is 15%.By studying age,clinicopathological characteristics and molecular classification,age at menarche,age at birth,number of births,number of miscarriages,lactation time,surgical history of benign breast lesions,history of gynecological diseases,and other factors,we retrospectively summarized and compared the disease history of patients with primary breast cancer and patients with benign thyroid tumors admitted to our hospital in the past 10 years to explore the clinicopathological characteristics and risk factors for primary breast cancer.AIM To investigate the clinical and pathological features and risk factors for primary breast cancer treated at our center in order to provide a reference for the prevention and treatment of breast cancer in the Zhuhai-Macao region.METHODS Through a retrospective case-control study,149 patients with primary breast cancer diagnosed and treated at Zhuhai Hospital of Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2013 to March 2020 were included as a case group,and 165 patients with benign breast tumors diagnosed and treated from January 2019 to March 2020 were included as a control group.The data collected included age,age at menarche,age at first birth,number of births,number of miscarriages,lactation time,history of surgery for benign breast lesions,history of familial malignant tumors,history of gynecological diseases,history of thyroid diseases,and the tumor characteristics of the patients in the case group including pathological diagnosis,pathological type,tumor size,lymph node metastasis,distant metastasis,stage,and molecular classification,among others.In the case group,the chi-square test was used to analyze the clinical and pathological features of patients in three age groups(<40,40-59,and≥60 years).A multifactor logistic regression analysis was used to analyze correlations between the two groups.RESULTS Among 149 patients with primary breast cancer,the average age was 48.20±12.06 years,and the proportion of patients at 40-59 years old was the highest,accounting for 61.8%of cases.The molecular type was mainly luminal B type,accounting for 69.2%of cases,and at the time of diagnosis,the tumor stage was mainly stage I/II,accounting for 62.4%of cases.There were no statistically significant differences in the distributions of tumor location,pathological type,tumor size,lymph node metastasis,stage,or molecular classification among the three age groups(<40,40-59,and≥60 years)(P≥0.05).The differences in the distribution of distant metastasis among the three age groups(<40,40-59,and≥60 years)were statistically significant(P<0.01).The differences in lactation time,history of familial malignant tumors,history of gynecological diseases,and history of thyroid diseases between the two groups were not statistically significant(P≥0.05).The differences in age at disease diagnosis,age at menarche,and history of surgery for benign breast lesions were statistically significant(P<0.01).The difference in age at first birth was also statistically significant(P<0.05).CONCLUSION The highest incidence of breast cancer in the Zhuhai-Macao region is present among women aged 40-59 years.There is a larger proportion of stage I/II patients,and the luminal B type is the most common molecular subtype.Distant metastasis occurs mainly in the≥60-year-old group at the first diagnosis;increased age,late age at menarche,and late age at first birth may be risk factors for primary breast cancer,and a history of surgery for benign breast lesions may be a protective factor for primary breast cancer.

Molecular mechanisms of Baihedihuang decoction as a treatment for breast cancer related anxiety:A network pharmacology and molecular docking study

BACKGROUND The therapeutic effects of a combination of Chinese medicines called Baihedihuang decoction(BD)have been clinically verified,although its molecular targets in breast cancer related anxiety remain unknown.AIM To explore the molecular mechanisms of BD for breast cancer related anxiety treatment.METHODS We used the Traditional Chinese Medicine Systems Pharmacology database to screen the active ingredients and potential targets of BD,and constructed the"drug-ingredient-target"network map with the help of Cytoscape 3.8 software.Also,we used the Online Mendelian Inheritance in Man,DrugBank,and Gencards databases to collect the disease targets of breast cancer related anxiety,and used the STRING platform to perform protein interaction analysis and construct the protein-protein interaction network.Metascape platform was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of key targets.Molecular docking technology was used to verify the drug component/target disease network.RESULTS We screened 16 active ingredients of BD for breast cancer related anxiety,with 113 target proteins.There are 931 disease targets of breast cancer related anxiety,and finally,43 key targets and 305 Kyoto Encyclopedia of Genes and Genomes pathways were generated.The main active ingredients of BD for breast cancer related anxiety are verbascoside,β-sitosterol,stigmasterol,catalpol,etc.CDK2,TP53,HTR2A,ESR1,etc.are its key targets,and the main involved signaling pathways may include neuroactive ligand-receptor interaction pathway,5-hydroxytryptaminergic synapse,P53 signaling pathway,cGMP-PKG signaling pathway,the cAMP signaling pathway,etc.Finally,molecular docking was performed with Vina software to validate the key active ingredients in BD with the selected key action targets.The molecular docking results showed that verbascoside,β-sitosterol,stigmasterol and CDK2 could stably bind and interact through amino acid residues SER249,ARG260,PRO228,ALA282,SER276,LYS273,ASN272,etc.CONCLUSION The therapeutic effect of BD for breast cancer related anxiety is multi-level,multi-target,and multi-pathway.The findings of this study provide ideas and basis for further research.

Clinical characteristics and prognosis of triple-negative breast cancer

Objective： We investigated the clinical characteristics, and the prognostic factors of triple-negative breast cancer. Methods： 130 triple-negative breast cancer patients were reviewed on clinical characteristics and prognosis. All cases were lack of expression of estrogen receptor, progesterone receptor, and HER2/neu determined by immunohistochemistry. Results： 17.1% of all breast cancer patients （774 cases） were triple-negative breast cancer, and 68.9% of triple-negative breast cancer patients （91 cases） were premenopausal. 53.8% of patients （71 cases） had the tumors with T2 size, and 39.4% of them （52 patients） had lymph node metastasis. The rate of relapse in patients with lymph node metastasis was obviously higher than that in patients without lymph node metastasis （P = 0.001）. The median time of follow-up was 63 months. 33 cases relapsed and 20 patients died. 23 patients had at least two organs metastasis. The 5-year disease-free and overall survival rates were 73.8% and 85.7%. Conclusion： Triple-negative breast cancer patients commonly have high rate of multiple distant metastasis in 2-3 years after treatment. The status of lymph node is the most important prognostic factor. The triple-negative breast caner patients with lymph node metastasis have poor prognosis.

Fang-Xia-Dihuang decoction inhibits breast cancer progression induced by psychological stress via down-regulation of PI3K/AKT and JAK2/STAT3 pathways:An in vivo and a network pharmacology assessment

Background:The development and prognosis of breast cancer are intricately linked to psychological stress.In addition,depression is the most common psychological comorbidity among breast cancer survivors,and reportedly,Fang-Xia-Dihuang decoction(FXDH)can effectively manage depression in such patients.However,its pharmacological and molecular mechanisms remain obscure.Methods:Public databases were used for obtaining active components and related targets.Main active components were further verified by ultra-high-performance liquid chromatography-high-resolution mass spectrometry(UPLC-HRMS).Protein–protein interaction and enrichment analyses were taken to predict potential hub targets and related pathways.Molecule docking was used to understand the interactions between main compounds and hub targets.In addition,an animal model of breast cancer combined with depression was established to evaluate the intervention effect of FXDH and verify the pathways screened by network pharmacology.Results:174 active components of FXDH and 163 intersection targets of FXDH,breast cancer,and depression were identified.Quercetin,methyl ferulate,luteolin,ferulaldehyde,wogonin,and diincarvilone were identified as the principal active components of FXDH.Protein–protein interaction and KEGG enrichment analyses revealed that the phosphoinositide-3-kinase–protein kinase B(PI3K/AKT)and Janus kinase/signal transducer and activator of transcription(JAK2/STAT3)signaling pathways played a crucial role in mediating the efficacy of FXDH for inhibiting breast cancer progression induced by depression.In addition,in vivo experiments revealed that FXDH ameliorated depression-like behavior in mice and inhibited excessive tumor growth in mice with breast cancer and depression.FXDH treatment downregulated the expression of epinephrine,PI3K,AKT,STAT3,and JAK2 compared with the control treatment(p<0.05).Molecular docking verified the relationship between the six primary components of FXDH and the three most important targets,including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),AKT,and STAT3.Conclusion:This study provides a scientific basis to support the clinical application of FXDH for improving depression-like behavior and inhibiting breast cancer progression promoted by chronic stress.The therapeutic effects FXDH may be closely related to the PI3K/AKT and JAK2/STAT3 pathways.This finding helps better understand the regulatory mechanisms underlying the efficacy of FXDH.

Dual-miRNA-Propelled Three-Dimensional DNA Walker for Highly Specific and Rapid Discrimination of Breast Cancer Cell Subtypes in Clinical Tissue Samples

Accurate discrimination of cell subtypes at the molecular level is especially important for cancer diagnosis,but no current method allows rapid and precise detection of breast cancer subtypes.Herein,we developed an elegant DNA walker for direct and rapid differentiation of breast cancer cell subtypes via detection of dual-miRNAs in clinical tissue samples.This DNA nanomachine can be specifically initiated by endogenous miR-21 and miR-31,and the sensitivity was dramatically improved due to the DNAzyme-mediated signal amplification.This DNA walker enabled rapid detection of double miRNA characteristics in different breast cell lines and also distinguished the fluctuations in a single cell.Applications of this DNAzyme-based nanomachine in vivo and in clinical samples were demonstrated for efficient detection of breast cancer subtypes,making the method generally applicable for precise management of cancers.