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1.
人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)是乳腺癌的生物标志物之一。近年研究表明以曲妥珠单抗德鲁特康(T-DXd)、曲妥珠单抗多卡木嗪(SYD985)为代表的新型抗体药物偶联物可能使HER2低表达乳腺癌患者受益。按照目前的评分系统,HER2低表达乳腺癌患者占所有乳腺癌总数一半以上,从靶向治疗中获益的患者或可达到60%~70%。然而,HER2低表达乳腺癌是否具有独特生物学特异性的临床亚型尚有争议。  相似文献   

2.
乳腺癌HER2 过度表达预后相关因素研究   总被引:2,自引:0,他引:2       下载免费PDF全文
 目的 研究乳腺癌患者HER2 过度表达与其他临床预后因素的相关性及对预后的影响。方法  收集我院2002 年1 月~2003 年12 月乳腺癌Ⅰ~ Ⅲ期患者共176 例,检测HER2 表达,与其他临床预 后因素进行相关分析;同时比较HER2 过度表达和阴性表达患者的预后。结果 本组患者HER2 过度 表达与PR( P = 0. 002) 、ER( P = 0. 031) 表达呈负相关,而与其他预后因素无相关性。多因素分析表明 HER2 是无病生存时间的独立预后因素( P = 0. 018) 。结论 HER2 过度表达可作为乳腺癌无病生存时 间的独立预后因素并指导乳腺癌的治疗。  相似文献   

3.
随着乳腺癌综合治疗水平的提高和抗肿瘤药物的不断发展,晚期乳腺癌患者的生存情况有了明显改善。乳腺癌进入精细分类、精确分层的新阶段,2022年晚期乳腺癌研究领域取得了多项突破性进展,各亚型治疗有了新的变化,研究结果影响诊疗指南,改变临床实践。激素受体阳性晚期乳腺癌的研究重点在于细胞周期蛋白依赖性激酶4和6(cyclindependentkinase4and6,CDK4/6)抑制剂治疗失败患者的治疗。人表皮生长因子受体2(humanepidermalgrowthfactor receptor 2,HER2)阳性晚期乳腺癌的治疗中新型抗HER2的抗体药物偶联物(antibody-drug conjugate,ADC)成为研究热点。晚期三阴性乳腺癌(triple-negative breast cancer,TNBC)中免疫治疗需要更多的研究证据,靶向Trop-2的ADC取得了一定疗效。HER2低表达晚期乳腺癌属于特定人群,ADC治疗正在改变临床实践模式。本文对2022年度不同类型晚期乳腺癌的研究进展进行总结,以期更好地指导晚期乳腺癌的治疗,改善患者预后。  相似文献   

4.
人表皮生长因子受体2(HER2)阳性乳腺癌因其侵袭性高、预后差而一直备受关注。随着曲妥珠单抗的应用,早期HER2阳性乳腺癌患者的预后已得到显著改善,由于其仍存在耐药性和不良反应,在标准治疗中加入新的抗HER2药物又成为新的研究重点,这些药物包括帕妥珠单抗、抗体药物偶联物曲妥珠单抗-美坦新(T-DM1)和各种小分子抑制剂(拉帕替尼、来那替尼、吡咯替尼)。同时PD1及PD-L1抑制剂如帕博利珠单抗在HER2阳性乳腺癌中的研究也在进行中,并有部分基础研究和病例报道已经证实了其疗效和安全性。本文旨在对目前HER2阳性乳腺癌的治疗方案和支持HER2阳性乳腺癌治疗的最新证据进行综述。  相似文献   

5.
结直肠癌(Colorectal cancer,CRC)是世界第三大常见癌症和第二大癌症相关死亡原因,严重威胁人类生命健康。尽管接受早期诊断和治疗,仍有相当部分结直肠癌患者因发生转移而预后较差。针对结直肠癌分子多样性的研究不但可指导预后,对患者个体化管理亦有重要参考意义。人表皮生长因子受体2(Human epidermal growth factor receptor-2,HER2)在乳腺癌、胃癌等多种恶性肿瘤中表达,抗HER2治疗能有效改善HER2阳性晚期乳腺癌、胃癌患者的预后。HER2作为转移性结直肠癌(metastatic colorectal cancer,mCRC)新兴的生物标志物近年来也备受关注。本文就目前HER2阳性mCRC的诊疗现状研究进展做一综述,以期为临床诊断、药物选择等提供参考。  相似文献   

6.
目的探讨黏蛋白1(mucin1,MUC1)强阳性表达在不同免疫表型乳腺癌中对指导预后及个体化治疗的意义。方法采用免疫组织化学法检测335例乳腺癌组织中ER、PR和HER2的表达,将乳腺癌分为四个免疫表型,采用免疫组织化学法测定各免疫表型中MUC1的阳性及强阳性表达情况,并对其与不同免疫表型乳腺癌预后的关系进行统计分析。结果 335例乳腺癌患者中MUC1强阳性表达率为46.3%,MUC1强阳性表达患者5年总生存率低于非强阳性表达者,两者之间差异存在统计学意义(P<0.05)。335例乳腺癌中ER+/PR+、HER2-型130例,ER+/PR+、HER2+型64例,ER-、PR-、HER2+型67例,ER-、PR-、HER2-型74例;MUC1强阳性表达率分别为59.2%、56.3%、32.8%和27.0%,MUC1强阳性表达与乳腺癌免疫表型相关(P<0.01)。预后分组分析表明ER+/PR+、HER2-型,ER-、PR-、HER2+型乳腺癌患者中,MUC1强阳性表达患者5年总生存率低于非强阳性表达者,差异有统计学意义(P<0.05)。结论 MUC1强阳性表达与乳腺癌免疫表型相关,在不同免疫表型乳腺癌预后中的作用也有所不同,在ER+/PR+、HER2-型及ER-、PR-、HER2+型乳腺癌中MUC1强阳性表达提示预后较差。  相似文献   

7.
摘 要: [目的] 比较早期乳腺癌中不同人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)蛋白表达患者的临床病理特征及预后的差异性。[方法] 收集2010年6月至2019年6月内蒙古医科大学附属医院甲状腺乳腺外科收治的792例Ⅰ~Ⅱ期乳腺癌患者的临床病理资料,入组患者根据HER2蛋白表达水平分为HER2不表达301例、HER2低表达309例、HER2阳性182例三组,回顾性分析不同HER2亚组患者临床病理特征及预后的差异性。[结果] HER2低表达患者主要以Luminal A型为主,三阴性乳腺癌(triple-negative breast cancer,TNBC)所占比例较低。与HER2不表达患者相比,HER2低表达患者腋窝淋巴结阳性、脉管癌栓及激素受体(hormone receptor,HR)阳性所占比例较高,浸润性小叶癌、组织学分级以及Ki-67高表达所占比例较低。共随访792例患者,中位随访时间为56个月,HER2阳性、HER2低表达、HER2不表达患者5年无病生存率(disease free survival,DFS)分别为85.7%、92.9%、91.3%(?字2=8.268,P=0.016),5年总生存率(overall survival,OS)分别为92.8%、97.4%、96.8%(?字2=15.809,P<0.001),按HR状态分层分析后5年DFS差异也无统计学意义。[结论] 虽然HER2低表达乳腺癌具有独特的临床病理特征,但并未导致HER2低表达和HER2不表达乳腺癌预后差异。研究结果支持HER2低表达乳腺癌作为独立的生物学亚型。  相似文献   

8.
人表皮生长因子受体2(HER2)在20%~30%的乳腺癌患者中过表达.针对HER2的分子靶向治疗可从分子水平抑制乳腺癌细胞生长.目前乳腺癌的分子靶向治疗药物主要有作用于HER2的单克隆抗体和酪氨酸激酶抑制剂两类.曲妥珠单抗已临床用于治疗HER2阳性的转移性乳腺癌,对HER2阳性的早期乳腺癌也有一定疗效.拉帕替尼对难治性乳腺癌和乳腺癌脑转移的治疗有很大潜力.该类药物在乳腺癌治疗领域中存在着巨大潜力.  相似文献   

9.
目的 乳腺癌的治疗已经进入分子分型时代,雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)和人类表皮生长因子受体-2(human epidermal growth factor receptor 2,HER2)的表达对指导制订乳腺癌治疗方案及评价患者预后等尤为重要.许多研究证实,部分乳腺癌患者原发灶及转移灶激素受体与HER2表达存在差异,影响术后辅助及解救治疗方案的制订,进而影响患者的治疗效果及预后.本研究探讨乳腺癌原发灶与腋窝及远处转移灶之间激素受体与HER2表达的差异及其临床意义,同时分析了造成差异的影响因素.方法 以乳腺癌、激素受体(ER和PR)、HER2、原发灶和转移灶为关键词,检索PubMed、CNKI数据库和万方数据库1995-01-2016-10的相关文献.共505篇文章被检索到.纳入标准:原发灶与腋窝转移灶激素受体及HER2表达差异情况,原发灶与远处转移灶激素受体及HER2表达差异情况,原发灶与转移灶激素受体及HER2表达差异情况的临床意义.根据纳入标准最终纳入分析38篇文献.结果 在部分乳腺癌患者中,原发灶与腋窝转移灶及远处转移灶激素受体及HER2表达情况存在差异,多数文献报道,乳腺癌原发灶与转移灶ER表达状况变化(阳性转阴性或阴性转阳性)比例约为20%,PR约为20%,HER2约为15%.“肿瘤异质性、抗肿瘤治疗和检测方法”等是影响其表达差异的影响因素.结论 推荐对于存在局部及远处转移的乳腺癌患者,同时检测并综合原发灶及转移灶的激素受体及HER2表达情况制订治疗方案.  相似文献   

10.
乳腺癌中有20%~30%的患者表达HER2基因,HER2阳性乳腺癌预后较差,易发生复发和转移。但HER2的表达为乳腺癌治疗提供了新方向。曲妥珠单抗是抗HER2治疗的经典基础药物,然而其原发继发耐药问题引起了大家的注意,研究发现其不敏感及耐药机制的发生可能与肿瘤细胞表面PD-L1上调相关。因此大量关于PD-1/PD-L1抑制剂联合曲妥珠单抗的研究展开意在提高其敏感度,改善其耐药问题。本文就PD-1/PD-L1抑制剂在HER2阳性乳腺癌的临床前及临床研究作一综述。  相似文献   

11.
背景与目的:乳腺癌是全球最常见的女性恶性肿瘤,且发病率仍在不断上升。乳腺癌的术后放疗可有效地改善局部控制率和长期生存率,放疗已成为乳腺癌治疗的主要技术。如何进一步减少患者正常组织的不良反应、提高放疗效果成为研究热点。探讨人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)和乳腺癌易感基因1(breast cancer susceptibility gene 1,BRCA1)在乳腺癌患者中的表达,并研究两者的表达与放疗敏感性的相关性,以期为临床治疗提供依据。方法:回顾并分析郑州大学附属肿瘤医院收治的156例乳腺癌患者的癌变组织和相邻正常乳腺组织的临床资料,并选取145例乳腺良性病变患者的良性乳腺病变组织作为对照。采用实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RTFQ-PCR)检测组织中HER2和BRCA1 mRNA表达,采用免疫组织化学法检测组织中HER2和BRCA1蛋白的水平。采用Spearman相关性分析HER2和BRCA1蛋白表达的关系,采用Kaplan-Meier生存分析评估乳腺癌术后放疗患者的生存率,探讨HER2和BRCA1表达与乳腺癌放疗患者预后的关系。结果:与相邻正常乳腺组织和良性乳腺病变组织相比,癌变组织HER2 mRNA和蛋白的表达上调(P<0.01),BRCA1 mRNA和蛋白表达下降(P<0.01)。放疗后,HER2阳性患者的局部失败率明显高于阴性患者(P<0.05),BRCA1阳性的局部失败率则明显低于阴性患者(P<0.01)。HER2阳性患者的5年生存率明显低于HER2阴性患者(P<0.01),BRCA1阳性患者的5年生存率则明显高于BRCA1阴性患者(P<0.01)。结论:高表达HER2和低表达BRCA1基因的乳腺癌患者对放疗的敏感性较低,为乳腺癌患者的临床治疗提供了新的理论依据。  相似文献   

12.
目的 激素受体阴性(ER-/PR-)乳腺癌具有明显的肿瘤异质性,临床治疗手段相对有限.本研究探讨激素受体阴性乳腺癌组织中,雄激素受体(androgen receptor,AR)和HER2表达的相关性,及其与临床病理参数和预后的相关性.方法 收集中国人民解放军福州总医院经手术治疗并病理确诊的乳腺癌120例,中位年龄52岁.采用FISH法检测收集的激素受体阴性乳腺癌组织HER2/neu基因状态,分为HER2阳性(HER2过表达组)和HER2阴性(三阴组)两组,每组60例.并采用EliVisionTM plus免疫组化法检测AR、Ki-67、EGFR表达,分析HER2和AR表达与临床病理参数、3年无病生存期(disease free survival,DFS)的相关性.结果 AR在激素受体阴性乳腺癌组织阳性率为61.67%(74/120),HER2过表达组和三阴组分别为73.33%(44/60)和50.00%(30/60).激素受体阴性乳腺癌组织中,AR表达与月经状态、肿瘤大小、组织学分级、EGFR表达及HER2状态相关,均P值<0.05;在HER2过表达组中,AR表达与月经状态、淋巴结受累、EGFR表达相关,均P值<0.05;三阴组中,AR表达与肿瘤大小和组织学分级相关,均P值<0.05.Kaplan-Meier法分析显示,HER2过表达组中AR表达与患者的3年DFS呈正相关,P<0.05;Cox回归法分析结果示,肿瘤大小、淋巴结受累、EGFR表达、AR表达均与患者的3年DFS有关,P<0.05.结论 AR可能成为筛选激素受体阴性乳腺癌高危人群和预测其预后的辅助指标之一,可作为激素受体阴性乳腺癌的新治疗靶点,为不同HER2状态乳腺癌治疗提供新思路.  相似文献   

13.
Therapeutic decision for adjuvant systemic therapy for breast cancer involves assessment of baseline risk and estimated benefit from systemic therapy. Molecular profiling studies have clearly demonstrated heterogeneity of chemotherapy response across different molecular subtypes of breast cancer. Meta-analyses of publicly available data from gene expression profiling studies have demonstrated that breast cancer can be divided into 4 basic categories based on expression levels of estrogen receptor (ER), HER2, and proliferation-associated genes; ER-, HER2+, ER+/HER2-/low proliferation, and ER+/HER2-/high proliferation. Notably ER- or HER2+ tumors are associated with high levels expression of proliferation genes, although there is a wide spectrum of expression levels of proliferation genes among ER+/HER2- tumors. Estrogen receptor-positive/HER2-/low-proliferation tumors are associated with a favorable prognosis. Synthetic lethal screening approach has demonstrated that most of the chemotherapeutic agents do not have specific molecular targets. Therefore, it could be hypothesized that chemosensitivity would be largely dictated by proliferation activity of tumor cells. Therefore, tumors with ER-, HER2+, or ER+/HER2-/high proliferation gene expression profile can be categorized as chemosensitive tumors, whereas ER+/HER-/low proliferation tumors categorized as chemoresistant. Therefore, clinical utility of gene expression profiling is mainly in aiding the chemotherapy decision for ER+ patients. Although evidence from prospective randomized clinical trials are lacking, because of the excellent baseline prognosis of patients with ER+/HER2-/low proliferation tumors when treated with endocrine therapy and because of scientific evidence of chemoresistance of these tumors, a comfort zone has been reached among oncologists to allow clinical use of gene expression tests to identify patients who do not require chemotherapy among node-negative ER+ patients. However, these tools are still probabilistic at best in their performances, and one cannot exactly predict which patient will have recurrence after assigned therapies until the time of recurrence. Therefore, strategies have to be established to identify patients who will fail standard chemoendocrine therapies among high-risk patients (ER+/HER2-/high proliferation, HER2+, or ER-) before recurrence events. Neoadjvant therapy can provide such venue because regardless of regimens used the prognosis of those achieving complete pathological response is excellent. Postneoadjuvant setting can be then used for patients with gross residual disease to test novel therapeutic agents.  相似文献   

14.
The aim of the study was to investigate the relationship between the expression of human epidermal growth factor receptor 2 (HER2) and activator protein 2 (AP-2), as well as the prognostic significance of HER2 in breast cancer. HER2 and AP-2 expressions were immunohistochemically (IHC) analysed in a large prospective, consecutive series of 425 breast cancer patients diagnosed and treated between 1990 and 1995 at the Kuopio University Hospital, Kuopio, Finland. In a subset of patients (n = 71), the gene amplification status was examined by using a chromogenic in situ hybridisation (CISH) analysis. Expression of HER2 was studied in relation to AP-2, clinicopathological parameters and patients' survival. Pathological membranous overexpression of the HER2 receptor was seen in 13% of the carcinomas, which was related both to gene amplification (78% of the cases) and high nuclear expression of AP-2 (67%, P = 0.007). HER2-positivity was most often seen in carcinomas having both high nuclear and high cytoplasmic AP-2 expression (P < 0.001). In the univariate survival analyses HER2-positivity predicted a shorter recurrence-free survival (RFS) (P < 0.0001) and a shorter breast cancer-related survival (BCRS) (P = 0.0063) in the whole patient group, as well as in the subgroup of node-negative patients. In the node-positive patients, HER2-positivity predicted only a shorter RFS. Combined expression of HER2 and nuclear AP-2 resulted in the separation of four groups with different prognoses, the best prognosis being for patients in the HER2-/AP-2+ group and the worse prognosis for those in the HER2+/AP-2- group. In the multivariate survival analyses, HER2-positivity independently predicted a shorter RFS in the whole patient group (P = 0.0067), as well as in the subgroup of node-positive patients (P = 0.0209). In conclusion, pathological membranous overexpression of the HER2 receptor in breast cancer is related both to gene amplification and a high AP-2 expression. Combining HER2 and AP-2 expressions may provide valuable information on the prognosis of breast cancer patients.  相似文献   

15.
Overexpression of the HER2/neu oncogene and receptor protein has been reported in 20%-30% of patients with breast cancer and is associated with a poor prognosis. HER2/neu expression in breast cancer patients assessed by fluorescence in situ hybridization or immunohistochemistry is a predictor for response to trastuzumab, a humanized monoclonal antibody against the HER2/neu cell-surface protein. Data regarding HER2/neu expression in lung cancer are more limited, and there is little information regarding HER2/neu expression and response to trastuzumab alone or in combination with chemotherapeutic agents. Gemcitabine is an active agent against non-small-cell lung cancer (NSCLC) and has demonstrated activity in breast cancer as well. In vitro modified tetrazolium salt growth assays were performed to determine whether the combination of trastuzumab/gemcitabine produced synergistic or additive effects on breast and lung cancer cell lines. The effects of trastuzumab alone, gemcitabine alone, and the trastuzumab/gemcitabine combination was evaluated on 4 NSCLC cell lines, 1 small-cell lung cancer (SCLC) cell line, and 2 breast cancer cell lines. HER2/neu surface protein expression was assessed by fluorescence flow cytometry and immunohistochemistry. Fluorescence in situ hybridization analysis was used to study gene expression. Trastuzumab treatment alone resulted in growth inhibition in all cell lines expressing HER2/neu and the inhibitive effect correlated with the level of cell surface HER2/neu protein expression. Treatment with gemcitabine alone resulted in growth inhibition in both breast and NSCLC cell lines. A synergistic growth inhibition effect was seen with the trastuzumab/ gemcitabine combination as indicated by combination index values < 1. The degree of synergy observed did not directly correlate with the level of surface protein expression, as synergy was seen even in cancer cell lines expressing low levels of HER2/neu. No treatment effect was seen in the SCLC cell line, which did not express HER2/neu. These preclinical studies indicate a need to study the clinical synergistic effects of the gemcitabine/trastuzumab combination in breast cancer and NSCLC patients whose tumors overexpress HER2/ neu.  相似文献   

16.
Human epidermal growth factor receptors (HERs) are known to play a pivotal role in breast cancer, both as prognostic markers and as therapeutic targets. The importance of Her4 expression is, however, still controversially discussed; there are few reports on the clinical significance of HER4, its splice variants, and cleaved HER4 intracellular domains (4ICD) which function differently depending on their localization in breast cancer. In 238 primary invasive breast cancer patients, we analyzed the expression levels of HER4 extracellular (JM-a and JM-b) and intracellular (CYT-1 and CYT-2) domains as well as 4ICD localization, and tested the relationship with clinicopathological characteristics and prognosis. The predominantly-expressed extracellular domain was JM-a, and lower CYT-2 dominance was a factor related to better relapse-free survival. CYT-2-dominance with higher nuclear 4ICD expression was a favorable prognostic marker especially in patients with the ER+ HER2- subtype treated with endocrine therapy. The absence of cytoplasmic 4ICD staining was related to better prognosis in CYT-1-dominant patients. In conclusion, analysis of splicing variants and 4ICD localization should be considered when targeting HER4 as a novel ER+/HER2- breast cancer treatment.  相似文献   

17.
ABSTRACT: BACKGROUND: Overexpression of the human epidermal growth factor receptor (HER) 2 is associated with poor prognosis and shortened survival in breast cancer patients. HER2 is a potent activator of several signalling pathways that support cell survival, proliferation and metabolism. In HER2-positive breast cancer there are most likely unexplored proteins that act directly or indirectly downstream of well established pathways and take part in tumour development and treatment response. METHODS: In order to identify novel copy number variations (CNVs) in HER2-positive breast cancer whole-genome single nucleotide polymorphism (SNP) arrays were used. A PCR-based loss of heterozygosity (LOH) assay was conducted to verify presence of deletion in HER2-positive breast cancer cases but also in HER2 negative breast cancers, cervical cancers and lung cancers. Screening for mutations was performed using single-strand conformation polymorphism (SSCP) followed by PCR sequencing. Protein expression was evaluated with immunohistochemistry (IHC). RESULTS: A common deletion at chromosome Xq24 was found in 80% of the cases. This locus harbours the gene solute carrier (SLC) family 25A member 43 (SLC25A43) encoding for a mitochondrial transport protein. The LOH assay revealed presence of SLC25A43 deletion in HER2-positive (48%), HER2-negative (9%), cervical (42%) and lung (67%) cancers. HER2-positive tumours with negative or low SLC25A43 expression had significantly lower S-phase fraction compared to tumours with medium or high expression (P = 0.024). CONCLUSIONS: We have found deletion in the SLC25A43 gene to be a common event in HER2-positive breast cancer as well as in other cancers. In addition, the SLC25A43 protein expression was shown to be related to S-phase fraction in HER2-positive breast cancer. Our results indicate a possible role of SLC25A43 in HER2-positive breast cancer and support the hypothesis of altered mitochondrial function in cancer.  相似文献   

18.
目的 分析免疫组化法与荧光原位杂交技术(Fish)两种检测方法对乳腺癌患者人类表皮生长因子受体2(HER2)表达水平的检测价值.方法 选择248例乳腺癌患者,分别使用免疫组化法和Fish法检测乳腺癌组织中HER2的表达情况,随访3年,采用生存曲线分析HER2阳性乳腺癌患者的术后复发率.结果108例(43.55%)患者的免疫组化结果为HER2(-),54例(21.77%)患者为HER2(+),43例(17.34%)患者为HER2(++), 43例(17.34%)患者为HER2(+++).81例(32.66%)患者的Fish检测结果为阳性,167例(67.34%)患者为阴性.免疫组化法和Fish法对乳腺癌患者HER2检测结果的一致性较好,Kappa=0.937,P=0.000.生存曲线显示Fish阳性的乳腺癌患者术后复发率明显高于Fish阴性的乳腺癌患者(P=0.000),免疫组化HER2阳性的乳腺癌患者术后复发率明显高于HER2阴性的乳腺癌患者(P=0.000).结论 免疫组化法和Fish法对乳腺癌患者HER2检测结果的一致性较好,均可较好地反映患者预后.  相似文献   

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