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人表皮生长因子受体2低表达乳腺癌及其相关药物治疗的研究进展

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中华肿瘤杂志 2021年第9期43卷 901-905页

作者：袁芃徐兵河国家癌症中心国家肿瘤临床医学研究中心中国医学科学院北京协和医学院肿瘤医院特需医疗部 100021 国家癌症中心国家肿瘤临床医学研究中心中国医学科学院北京协和医学院肿瘤医院药物临床试验研究中心 100021

乳腺癌是女性常见的恶性肿瘤之一,世界各地乳腺癌发病率居高不下。人表皮生长因子受体2(HER-2)是一种酪氨酸激酶受体,HER-2异常扩增或过度表达的乳腺癌具有侵袭性强、预后差的特点。随着抗HER-2药物的出现,HER-2阳性乳腺癌患者的生存期... 详细信息

乳腺癌是女性常见的恶性肿瘤之一,世界各地乳腺癌发病率居高不下。人表皮生长因子受体2(HER-2)是一种酪氨酸激酶受体,HER-2异常扩增或过度表达的乳腺癌具有侵袭性强、预后差的特点。随着抗HER-2药物的出现,HER-2阳性乳腺癌患者的生存期逐渐延长,患者预后得以改善,但传统HER-2靶向药物对HER-2低表达患者的疗效十分有限,HER-2低表达乳腺癌的治疗依然面临挑战。文章回顾了美国临床肿瘤学会和美国病理学家学会指南对于HER-2检测规范化的过程,提出了定义HER-2低表达乳腺癌这一新亚型的数据依据及可能。新一代HER-2靶向药物的诞生,为HER-2低表达患者的治疗提供新的选择,这将重新定义HER-2低表达乳腺癌,并为HER-2低表达乳腺癌患者预后改善提供新的机会。

关键词：乳腺肿瘤人表皮生长因子受体2低表达药物治疗

Expert consensus on the clinical application of PI3K/AKT/mTOR inhibitors in the treatment of advanced breast cancer

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Cancer Innovation 2022年第1期1卷 25-54页

作者： The Society of Clinical Research of Oncology Medications of China Anticancer Association Breast Cancer Expert Committee of National Cancer Quality Control Center Boao Cancer Innovation Institute Fei Ma binghe xu 不详 Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/CancerHospitalChinese Academy of MedicalSciences and Peking Union MedicalCollegeBejing 100021China Department of Medical Oncology and Clinical Trial Center National Cancer Center/National ClinicalResearch Center for Cancer/CancerHospitalChinese Academy of MedicalSciences and Peking Union MedicalCollegeBeijing 100021China

Phosphoinositide 3‐kinase(PI3K)/protein kinase B(PKB or AKT)/mammalian target of rapamycin(mTOR)signaling pathway(PAM pathway)plays an important role in the development of breast cancer and are closely associated with the resistance to endocrine therapy in advanced breast ***,anticancer treatment targeting key molecules in this signaling pathway has become a research hotspot in recent *** clinical trials have demonstrated that PI3K/AKT/mTOR inhibitors bring significant clinical benefit to patients with advanced breast cancer,especially to those with hormone receptor(HR)‐positive,human epidermal growth factor receptor(HER)2‐negative advanced breast ***,a PI3K inhibitor,and everolimus,an mTOR inhibitor,have been approved by *** on their high efficacy and relatively good safety profile,an expanded indication of everolimus in breast cancer has been approved by National Medical Products Administration(NMPA).Alpelisib is expected to be approved in China in the near *** members of the consensus expert panel reached this consensus to comprehensively define the role of PI3K/AKT/mTOR signaling pathway in breast cancer,efficacy and clinical applications of PI3K/AKT/mTOR inhibitors,management of adverse reactions,and PIK3CA mutation detection,to promote the understanding of PI3K/AKT/mTOR inhibitors for Chinese oncologists,improve clinical decision‐making,and prolong the survival of target patient population.

关键词： breast cancer PI3K/AKT/mTOR inhibitors

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新型抗Her-2药物T-DM1

中国肿瘤临床 2013年第19期40卷 1203-1206页

作者：岳健徐兵河北京协和医学院中国医学科学院肿瘤医院内科北京市100021

T-DM1是新型抗体-药物偶联物,具有曲妥珠单抗类似的生物活性,可特异性的将强效抗微管药物DM1释放至Her-2过表达的肿瘤细胞内。T-DM1单药疗效优于拉帕替尼联合卡培他滨,有望成为Her-2阳性晚期乳腺癌的标准二线治疗药物。比较T-DM1与曲妥... 详细信息

T-DM1是新型抗体-药物偶联物,具有曲妥珠单抗类似的生物活性,可特异性的将强效抗微管药物DM1释放至Her-2过表达的肿瘤细胞内。T-DM1单药疗效优于拉帕替尼联合卡培他滨,有望成为Her-2阳性晚期乳腺癌的标准二线治疗药物。比较T-DM1与曲妥珠单抗联合紫杉类药物一线治疗晚期乳腺癌的试验正在进行中。该药是继曲妥珠单抗之后又一种全新的抗Her-2药物。美国FDA正式批准T-DM1作为治疗Her-2阳性晚期乳腺癌患者的药物。

关键词： T—DM1 乳腺癌 Her-2阳性抗体-药物偶联物

The prognostic and therapeutic implications of circulating tumor cell phenotype detection based on epithelial-mesenchymal transition markers in the first-line chemotherapy of HER2-negative metastatic breast cancer

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Cancer Communications 2019年第1期39卷 1-10页

作者： Xiuwen Guan Fei Ma Chunxiao Li Shiyang Wu Shangying Hu Jiefen Huang Xiaoying Sun Jiayu Wang Yang Luo Ruigang Cai Ying Fan Qiao Li Shanshan Chen Pin Zhang Qing Li 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 CollegeNo.17Panjiayuan NanliChaoyang DistrictBeijing 100021P.R.China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China SurExam Bio-Tech Guangzhou Technology Innovation BaseScience CityGuangzhou 510000GuangdongP.R.China Department of Cancer Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Department of Medical Oncology Huanxing Cancer HospitalBeijing 100021P.R.China

Background:Epithelial-mesenchymal transition(EMT)is implicated in the metastatic process and presents a chal-lenge to epithelial cell adhesion molecule-based detection of circulating tumor cells(CTCs),which have been demon-strated to be a prognostic indicator in metastatic breast *** evidence has indicated that heterogeneity of CTCs based on EMT markers is associated with disease progression,no standard recommendations have been established for clinical *** study aimed to evaluate the prognostic significance of dynamic CTC detection based on EMT for metastatic breast cancer ***:We enrolled 108 human epidermal growth factor receptor 2-negative metastatic breast cancer patients from the prospective phase III CAMELLIA study and applied the CanPatrol CTC enrichment technique to identify CTC phenotypes(including epithelial CTCs,biphenotypic epithelial/mesenchymal CTCs,and mesenchymal CTCs)in peripheral blood *** operating characteristic curve analyses of total CTC count and the proportion of mesenchymal CTCs for predicting the 1-year progression-free survival(PFS)rate were conducted to determine the optimal cut-off values,and Kaplan-Meier analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic value of the cut-off values of both total CTC count and the proportion of mesenchymal CTCs in ***:For predicting the 1-year PFS rate,the optimal cut-off value of total CTC count was 9.5(Area under the curve[AUC]=0.538,95%confidence interval[CI]=0.418-0.657),and that of the proportion of mesenchymal CTCs was 10.7%(AUC=0.581,95%CI=0.463-0.699).We used the two cut-off values in combination to forecast PFS in which the total CTC count was equaled to or exceeded 10/5 mL with the proportion of mesenchymal CTCs surpassed 10.7%.Patients who met the combined criteria had significantly shorter median PFS than did those who did not meet the criteria(6.2 vs.9.9 months,P=0.010).A nomog

关键词： Breast cancer Circulating tumor cells Epithelial-mesenchymal transition Prognosis Therapeutic implication

Treatment patterns and clinical outcomes in patients with metastatic breast cancer treated with palbociclib-based therapies:real-world data in the Han population

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Chinese Medical Journal 2022年第14期135卷 1734-1741页

作者： Hongnan Mo Fei Ma Qing Li Pin Zhang Peng Yuan Jiayu Wang Yang Luo Ruigang Cai Qiao 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

Background:This study aimed to reveal the treatment patterns and clinical outcomes of diverse palbociclib-based regimens in Han patients with estrogen receptor-positive(ER+)metastatic breast cancer in routine clinical ***:The clinical data of patients with ER+metastatic breast cancer treated with palbociclib were collected from the National Cancer Center *** efficacy profile of palbociclib in this Han population was evaluated,especially for various combination *** efficacy of palbociclib-based therapy in patients with prior everolimus treatment was also ***:A total of 186 patients from 89 cities in 18 provinces in China were *** median progression-free survival(PFS)was similar among different palbociclib-combined groups(P=0.566):10.0 months(95%confidence interval[CI]3.8-16.1)in the+exemestane group,9.7 months(95%CI 6.3-13.1)in the+letrozole group,7.8 months(95%CI 5.5-10.2)in the+fulvestrant group,7.2 months(95%CI 3.2-11.3)in the+toremifene group,and 6.1 months(95%CI 1.2-11.0)in the+anastrozole ***-four patients(18.3%)had received everolimus for their metastatic disease before the prescription of *** disease control rate was significantly lower in patients who had received previous everolimus than in the everolimus-naïve group(50.0%vs.82.2%,P<0.001).Patients pre-treated with everolimus had significantly worse PFS than those in the everolimus-naïve group(3.4 months vs.8.8 months,P=0.001).After propensity score matching,patients pre-treated with everolimus had similar PFS(4.4 months,95%CI 0.5-8.2)compared with everolimus-naïve patients(6.1 months,95%CI 4.7-7.5,P=0.439).Conclusions:Various palbociclib-based regimens have promising efficacy in ER+metastatic breast cancer in real-world settings,even in patients who had been pre-treated with everolimus.

关键词： Metastatic breast cancer Palbociclib Progression-free survival Real-world data

Irinotecan plus S-1 versus S-1 in patients with previously treated recurrent or metastatic esophageal cancer(ESWN 01):a prospective randomized,multicenter,open-labeled phase 3 trial

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Cancer Communications 2019年第1期39卷 151-160页

作者： Jing Huang binghe xu Ying Liu Junxing Huang Ping Lu Yi Ba Lin Wu Yuxian Bai Shu Zhang Jifeng Feng Ying Cheng Jie Li Lu Wen Xianglin Yuan Changwu Ma Chunhong Hu Qingxia Fan Xi Wang Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNo 17 Panjiayuan NanliChaoyang DistrictBeijing 100021P.R.China Department of Medical Oncology Henan Cancer HospitalZhengzhou 450008HenanP.R.China Department of Medical Oncology Taizhou People’s HospitalTaizhou 225300JiangsuP.R.China Department of Medical Oncology First Affiliated Hospital of Xinxiang Medical UniversityXinxiang 453100HenanP.R.China Department of Medical Oncology Tianjin Cancer HospitalTianjin 300060P.R.China Department of Medical Oncology Hunan Cancer HospitalChangsha 410006HunanP.R.China Department of Medical Oncology Harbin Medical University Cancer HospitalHarbin 150040HeilongjiangP.R.China Department of Medical Oncology Shandong Cancer HospitalJinan 250117ShandongP.R.China Department of Medical Oncology Jiangsu Cancer HospitalNanjing 210009JiangsuP.R.China Department of Medical Oncology Jilin Cancer HospitalChangchun 130012JilinP.R.China Department of Radiotherapy Shanxi Cancer HospitalTaiyuan 030013ShanxiP.R.China Department of Medical Oncology Shanxi Cancer HospitalTaiyuan 030013ShanxiP.R.China Department of Medical Oncology Tongji HospitalWuhan 430030HubeiP.R.China Department of Medical Oncology Chifeng Municipal HospitalChifeng 024000Inner MongoliaP.R.China Department of Oncology The Second Xiangya Hospital of Central South UniversityChangsha 410011HunanP.R.China Department of Oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052HenanP.R.China

Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been *** aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum-or taxane-based ***:We conducted a prospective randomized,multicenter,open-label,phase 3 trial in 15 centers across *** patients were adults with histologically confirmed recurrent or metastatic ESCC,and were randomly assigned(ratio,1:1)to receive either irinotecan plus S-1(intravenous infusion of irinotecan[160 mg/m2]on day 1 and oral S-1[80-120 mg]on days 1-10,repeated every 14 days)or oral S-1 monotherapy(80-120 mg/day on days 1-14,repeated every 21 days)using a central computerized minimization *** primary endpoint was progression-free survival(PFS).Results:Between December 23,2014 and July 25,2016,we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen(n=61)or S-1 monotherapy(n=62).After a median follow-up of 29.2 months(95%confidence interval[CI]17.5-40.9 months),the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group(3.8 months[95%CI 2.9-4.3 months]vs.1.7 months[95%CI 1.4-2.7 months],hazard ratio=0.58,95%CI 0.38-0.86,P=0.006).The objective response rates were 24.6%in the irinotecan plus S-1 group and 9.7%in the S-1 monotherapy group(P=0.002).The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia(16.4%vs.0%),neutropenia(14.8%vs.1.6%),and nausea(4.9%vs.0%).No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both ***: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- o

关键词： Esophageal squamous cell carcinoma Recurrent Metastasis Multicenter open-label randomized trial Irinotecan S-1 Overall survival Progression-free survival Objective response rate Disease control rate

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微小RNA基因多态与乳腺癌易感性的关系

中华肿瘤杂志 2015年第7期37卷 501-507页

作者：张萍马飞徐兵河中国医学科学院北京协和医学院肿瘤医院肿瘤内科 100021

目的探讨微小RNA（miRNA）基因序列的单核苷酸多态（SNP）位点与乳腺癌患病风险之间的关系，以期分析可用于易感人群筛查的分子标志物。方法选取经病理证实的乳腺癌患者（病例组）384例，选取与病例组患者年龄匹配的正常健康对照（对照... 详细信息

目的探讨微小RNA（miRNA）基因序列的单核苷酸多态（SNP）位点与乳腺癌患病风险之间的关系，以期分析可用于易感人群筛查的分子标志物。方法选取经病理证实的乳腺癌患者（病例组）384例，选取与病例组患者年龄匹配的正常健康对照（对照组）192例，均为汉族、女性，均经5年以上随诊证实无恶性肿瘤病史。根据美国国立生物技术信息中心和microRNA Base公共数据库信息，选择已知汉族人群中全部miRNA最小等位基因频率〉0．05的SNP位点，最终入选22条miRNA基因的23个位点。采用高通量的MassARRAY时间飞行质谱生物芯片系统分析候选位点的基因型。采用非条件Logistic回归模型评估候选位点与乳腺癌患病风险的关系。结果全组研究对象年龄21～81岁，中位年龄48岁。病例组患者的年龄分布、吸烟状态与对照组比较，差异均无统计学意义（均P〉0．05）。病例组和对照组伴有乳腺癌或卵巢癌家族史者所占比例分别为9．1％和1．6％，初潮年龄≤14岁所占比例分别为53．1％和37．5％，未绝经者所占比例分别为61．2％和50．0％，差异均有统计学意义（均P〈0．05）。病例组miRNA基因SNP位点各基因型的分布频率与对照组比较，差异无统计学意义（P〉0．05）。结论存在于miRNA基因序列的SNP与汉族、女性乳腺癌患病风险无明显相关性。

关键词：乳腺肿瘤微RNAs 多态性单核苷酸疾病遗传易感性

High BRCA1 expression is an independent prognostic biomarker in LUAD and correlates with immune infiltration

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Cancer Innovation 2023年第2期2卷 91-95页

作者： Fengzhu Guo Cong Li Shuning Liu Zhijun Li Jingtong Zhai Zhiwu Wang 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 CollegeBeijingChina Department of Medical Oncology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijingChina Department of Chemoradiotherapy Tangshan People's HospitalTangshanChina

Non-small-cell lung cancer(NSCLC)is the primary histopathological subtype of lung cancer and accounts for around 82%of all pulmonary neoplasms[1].Breast cancer susceptibility gene 1(BRCA1)is a tumor suppressor gene that regulates cellular responses to stress through DNA damage repair and is frequently mutated in breast and ovarian cancers[2].Furthermore,previous studies have increasingly shown that the expression of BRCA1 and the relevant poly(ADP-ribose)polymerase inhibitors is related to the prognosis and therapeutic response of other tumors,including lung cancer[3,4].However,previous findings on the prognostic value of BRCA1 for NSCLC have been inconsistent or conflicting,which may be attributed to the small number of patients from a single center or disparity in the ratio of patients with lung adenocarcinoma(LUAD)versus squamous cell carcinoma(LUSC)[5].The aim of this study was to determine the prognostic value of BRCA1 in NSCLC and its association with immune infiltration.

关键词： bioinformatics analysis lung adenocarcinoma meta-analysis non-small-cell lung cancer prognosis

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乳腺癌芳香化酶抑制剂耐药的研究进展

中国癌症杂志 2021年第2期31卷 81-89页

作者：李芷君徐兵河国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院肿瘤内科北京100021

乳腺癌是女性常见的恶性肿瘤,约70%的患者为雌激素受体(estrogen receptor,ER)和(或)孕激素受体(progesterone receptor,PR)阳性,内分泌治疗是激素受体(hormone receptor,HR)阳性乳腺癌的主要治疗方式之一。近几十年来,内分泌治疗药物... 详细信息

乳腺癌是女性常见的恶性肿瘤,约70%的患者为雌激素受体(estrogen receptor,ER)和(或)孕激素受体(progesterone receptor,PR)阳性,内分泌治疗是激素受体(hormone receptor,HR)阳性乳腺癌的主要治疗方式之一。近几十年来,内分泌治疗药物不断发展并应用于临床,乳腺癌患者的复发转移风险显著降低,预后得到长足改善。芳香化酶抑制剂(aromatase inhibitor,AI)在乳腺癌内分泌治疗中发挥重要作用,然而绝大部分患者会发生原发性或继发性耐药,因此克服内分泌治疗药物耐药对进一步提高临床疗效至关重要。从遗传学、表观遗传学及细胞内信号转导通路等方面对HR阳性乳腺癌患者AI治疗后耐药的机制及最新的研究进展进行综述,以期为临床诊疗及科研提供参考。

关键词：乳腺肿瘤芳香化酶抑制剂耐药机制治疗