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Breast cancer:an up-to-date review and future perspectives

Cancer Communications 2022年第10期42卷 913-936页

作者： Ruoxi Hong Binghe Xu Department of Medical Oncology Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060P.R.China State Key Laboratory of Molecular Oncology and Department of Medical Oncology Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100006P.R.China

Breast cancer is the most common cancer worldwide.The occurrence of breast cancer is associated with many risk factors,including genetic and hereditary predisposition.Breast cancers are highly heterogeneous.Treatment strategies for breast cancer vary by molecular features,including activation of human epidermal growth factor receptor 2(HER2),hormonal receptors(estrogen receptor[ER]and progesterone receptor[PR]),gene mutations(e.g.,mutations of breast cancer 1/2[BRCA1/2]and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha[PIK3CA])and markers of the immune microenvironment(e.g.,tumor-infiltrating lymphocyte[TIL]and programmed death-ligand 1[PDL1]).Early-stage breast cancer is considered curable,for which local-regional therapies(surgery and radiotherapy)are the cornerstone,with systemic therapy given before or after surgery when necessary.Preoperative or neoadjuvant therapy,including targeted drugs or immune checkpoint inhibitors,has become the standard of care for most early-stage HER2-positive and triple-negative breast cancer,followed by risk-adapted post-surgical strategies.For ER-positive early breast cancer,endocrine therapy for 5-10 years is essential.Advanced breast cancer with distant metastases is currently considered incurable.Systemic therapies in this setting include endocrine therapy with targeted agents,such as CDK4/6 inhibitors and phosphoinositide 3-kinase(PI3K)inhibitors for hormone receptor-positive disease,anti-HER2 targeted therapy for HER2-positive disease,poly(ADP-ribose)polymerase inhibitors for BRCA1/2 mutation carriers and immunotherapy currently for part of triple-negative disease.Innovation technologies of precision medicine may guide individualized treatment escalation or de-escalation in the future.In this review,we summarized the latest scientific information and discussed the future perspectives on breast cancer.

关键词： PIK3CA Breast cancer

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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

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Frontiers of Medicine 2021年第2期15卷 208-220页

作者： Wenjie Zhu Binghe Xu National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciencesand Peking Union Medical CollegeBeijing 100021China

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.

关键词： endocrine-resistant HR^(+)/HER2^(-)advanced breast cancer randomized clinical trials meta-analysis targeted therapy

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Progress in systemic therapy for triple-negative breast cancer

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Frontiers of Medicine 2021年第1期15卷 1-10页

作者： Hongnan Mo Binghe Xu Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Triple-negative breast cancer(TNBC)is the most aggressive subtype of breast cancer with a heterogeneous genetic profile.Chemotherapy exhibits substantial activity in a small subset of these patients.Drug resistance is inevitable.Major progress has been made in the genetic analysis of TNBC to identify novel targets and increase the precision of therapeutic intervention.Such progress has translated into major advances in treatment strategies,including modified chemotherapy approaches,immune checkpoint inhibitors,and targeted therapeutic drugs.All of these strategies have been evaluated in clinical trials.Nevertheless,patient selection remains a considerable challenge in clinical practice.

关键词： triple-negative breast cancer immunotherapy targeted therapy

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Breast cancer: Epidemiology, risk factors and screening

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Chinese Journal of Cancer Research 2023年第6期35卷 565-583页

作者： Hangcheng xu Binghe Xu Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Breast cancer is a global health concern with a significant impact on the well-being of women. Worldwide, the past several decades have witnessed changes in the incidence and mortality of breast cancer. Additionally,epidemiological data reveal distinct geographic and demographic disparities globally. A range of modifiable and non-modifiable risk factors are established as being associated with an increased risk of developing breast cancer.This review discusses genetic, hormonal, behavioral, environmental, and breast-related risk factors. Screening plays a critical role in the effective management of breast cancer. Various screening modalities, including mammography,ultrasound, magnetic resonance imaging(MRI), and physical examination, have different applications, and a combination of these modalities is applied in practice. Current screening recommendations are based on factors including age and risk, with a significant emphasis on minimizing potential harms to achieve an optimal benefits-to-harms ratio. This review provides a comprehensive insight into the epidemiology, risk factors, and screening of breast cancer. Understanding these elements is crucial for improving breast cancer management and reducing its burden on affected individuals and healthcare systems.

关键词： Breast neoplasms epidemiology mass screening risk factors

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Preface to Special Issue: Cancer epidemiology, risk factors and screening

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Chinese Journal of Cancer Research 2023年第6期35卷 563-564页

作者： Binghe Xu Hangcheng xu Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Cancer continues to be one of the leading causes of morbidity and mortality worldwide, posing significant challenges to public health systems. The International Agency for Research on Cancer(IARC) revealed an increase... 详细信息

关键词： Cancer epidemiology mortality

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A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 46-54页

作者： Pin Zhang Lin Wang Yueying Zhen Zhihong Wang Hesheng Zhang Richard Jones Binghe Xu Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Tianjin Hemay Pharmaceutical Co. LTDTianjin 300308China

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles.Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 months.Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

关键词： Advanced breast cancer HER2-positive Hemay022 first-in-human trial

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An immunogenic cell death-related signature for prediction of prognosis and response to immunotherapy in breast cancer

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Chinese Medical Journal 2024年第4期137卷 487-489页

作者： Cong Li Fengzhu Guo Jingtong Zhai Xiaohan Liu Zhijun Li Binghe Xu Department of Medical Oncology National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China Department of Medical Oncology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Department of Histology and Embryology Basic Medical CollegeChina Medical UniversityShenyangLiaoning 110122China

To the Editor:Tumor immune microenvironment plays a key role in breast cancer development and progression,which determines the long-term survival of breast cancer patients.Recent data have revealed that the application of cancer immunotherapy has some limitations,including generating weak immune responses due to inadequate delivery of immunostimulants to the immune cells.^([1])Thus,current clinical efforts are primarily focused on developing immune-based chemotherapy that can convert non-responders to responders.^([2])Immunogenic cell death(ICD)is a form of regulated cell death that is sufficient to activate an adaptive immune response.

关键词： breast immunotherapy chemotherapy

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Predictive biomarkers of response and survival following immunotherapy with a PD-L1 inhibitor benmelstobart(TQB2450)and antiangiogenic therapy with a VEGFR inhibitor anlotinib for pretreated advanced triple negative breast cancer

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Signal Transduction and Targeted Therapy 2023年第12期8卷 5944-5953页

作者： Yiqun Han Jiayu Wang Tao Sun Quchang Ouyang Jianwen Li Jie Yuan Binghe Xu National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Liaoning Cancer Hospital&Institute ShenyangLiaoning 110042China Hunan Cancer Hospital ChangshaHunan 410013China Geneplus-Shenzhen Shenzhen 518118China

In our phase Ib trial(ClinialTrials.gov Identifier:NCT03855358),benmelstobart(TQB2450),a novel humanized IgG1 antibody against PD-L1,plus antiangiogenic multikinase inhibitor,anlotinib,demonstrated promising antitumor activities in pretreated triple negative breast cancer(TNBC)patients.We conducted explorative analyses of genomic biomarkers to explore the associations with treatment response and survival outcomes.Targeted next generation sequencing(NGS)was undertaken toward circulating tumor DNA(ctDNA)collected from peripheral blood samples prior to the start of treatment and after disease progression.A total of 31 patients received targeted NGS and functional driver mutations in 29 patients were analyzed.The most frequent mutations were TP53(72%),MLL3(28%),and PIK3CA(17%).At a blood-based tumor mutational burden(bTMB)cutoff of 6.7 mutations per megabase,patients with low bTMB showed better response to anlotinib plus TQB2450(50%vs.7%,P=0.015)and gained greater PFS benefits(7.3 vs.4.1 months,P=0.012)than those with high bTMB.At a maximum somatic allele frequency(MSAF)cutoff of 10%,a low MSAF indicated a better objective response(43%vs.20%)as well as a significantly longer median PFS(7.9 vs.2.7 months,P<0.001).Patients with both low MSAF and low bTMB showed a notably better objective response to anlotinib plus TQB2450(70%vs.11%,P<0.001)and a significantly longer median PFS(11.0 vs.2.9 months,P<0.001)than patients with other scenarios.Our findings support future studes and validation of MSAF and the combined bTMB-MSAF classification as predictive biomarkers of immune checkpoint inhibitor-based regimens in advanced TNBC patients.

关键词： PIK3CA breast cancer

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Advances in medical treatment of breast cancer in 2022

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Cancer Innovation 2023年第1期2卷 1-17页

作者： Jingtong Zhai Yun Wu Fei Ma Virginia Kaklamani Binghe Xu Department of Medical Oncology National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Division of Hematology OncologyUT Health San Antonio MD Anderson Cancer CenterSan AntonioTexasUSA

Breast cancer has replaced lung cancer as the most common malignancy worldwide.The 5‐year survival rate of breast cancer has reached 90%.Systemic treatment of breast cancer has developed into a mature system including chemotherapy,targeted therapy,endocrine therapy and immunotherapy.This article summarizes the annual progress of breast cancer chemotherapy,targeted therapy,endocrine therapy and immunotherapy in 2022,providing valuable information for future research to better guide individualized treatment of breast cancer,thereby improving the prognosis and quality of life of breast cancer patients.

关键词： breast cancer chemotherapy targeted therapy endocrine therapy immunotherapy

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Validity of distress thermometer for screening of anxiety and depression in family caregivers of Chinese breast cancer patients receiving postoperative chemotherapy

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Chinese Journal of Cancer Research 2020年第4期32卷 476-484页

作者： Min Yang Fei Ma Bo Lan Jianqiang Cai Xiaoying Sun Binghe Xu Comprehensive Oncology Department National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Medical Oncology Cancer Hospital of Huanxing Chaoyang DistrictBeijing 100122China

Objective:Family caregivers(FCs)of breast cancer patients play a vital role throughout the treatment process.Psychological distress of FCs is common and often ignored.A simple and effective instrument for screening psychological distress would help in selecting those FCs requiring special attention and intervention.Here,the validity of distress thermometer(DT)in FCs of Chinese breast cancer patients receiving postoperative chemotherapy was assessed,and the prevalence of anxiety and depression was evaluated.Methods:We recruited 200 FCs of hospitalized breast cancer patients in this cross-sectional descriptive study.Before the first cycle of adjuvant chemotherapy,the levels of anxiety and depression among FCs were assessed using DT and Hospital Anxiety and Depression Scale(HADS).In total,191 valid cases were analyzed.HADS was used as the diagnostic standard to assess the effectiveness of DT as a screening tool for anxiety and depression as well as to analyze the diagnostic efficiency of DT at various cutoff points.Results:The definitive prevalence of both anxiety and depression was 8.90%.The mean level of anxiety and depression among FCs was 5.64±3.69 and 5.09±3.85,respectively,both of which were significantly higher than corresponding Chinese norms(P<0.01).The areas under receiver operating characteristic curves of DT for the diagnoses of FCs'anxiety and depression were 0.904 and 0.885,respectively.A cutoff value of 5 produced the best diagnostic effects of DT for anxiety and depression.Conclusions:The levels of both anxiety and depression were higher in the FCs of Chinese breast cancer patients receiving postoperative chemotherapy than the national norm.DT might be an effective tool to initially screen psychological distress among FCs.This process could be integrated into the palliative care of breast cancer patients and warrant further research.

关键词： Breast cancer distress thermometer anxiety depression

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