表皮生长因子受体2和雌激素受体及孕激素受体在乳腺癌中的表达及相关性分析

目的 探讨表皮生长因子受体2(HER2)和雌激素受体(ER)及孕激素受体(PR)在乳腺癌中的表达及相关性,并提出HER2 检测的优化程序,从而有利于HER2 检测的准确性和可重复性,更准确地筛选出适用Herceptin 靶向基因治疗的患者.方法 免疫组织化学SP 三步法对113 例广东地区乳腺癌患者HER2 、ER 、PR 表达进行检测.结果 在本组113 例乳腺癌患者中HER2 表达的阳性率为24.78 %,ER 表达的阳性率为61.95 %,PR 表达的阳性率为67.26 %,HER2 表达与乳腺癌TNM 分期、患者年龄、淋巴结转移、肿瘤大小无关(P ＞0.05 );HER2 表达与ER 、PR 表达情况有关(P ＜0.01 ),且呈负相关.结论 广东地区女性乳腺癌HER2 和ER 及PR 之间的表达相互关联,并在乳腺癌的确定治疗对策中扮演着重要角色.HER2检测的准确性和重复性,有赖于如何优化HER2 状况检测程序.     

赫赛汀联合TC方案用于乳腺癌患者化疗的护理

赫赛汀是一个新型的生物分子靶向治疗乳腺癌的新药,其有效成分是曲妥珠单抗,是一个重组的人源性抗P185Her2的单克隆抗体。化疗联合赫赛汀靶向治疗证明有着良好的临床疗效,使预后很差的HER2(人体表皮生长因子受体2)阳性的乳腺癌患者的生存率和生活质量有了显著提高。     

乳腺癌中分子病理学的应用及进展

肿瘤临床试验虽为肿瘤的诊断、治疗提供了有效的证据,但尚缺乏对特定个体提供适合的方案.对于乳腺癌患者,雌激素受体(ER)表达阳性和阴性与否,人表皮生长因子受体2(HER2)是否过表达,这些肿瘤细胞分子对于乳腺癌的诊断、治疗、预后以及预防具有重大意义.     

循环miRNA在乳腺癌诊断中的应用价值

乳腺癌是女性最为常见的恶性肿瘤,其发病率呈快速增长趋势,已成为威胁女性健康的严重疾病。乳腺癌的早期诊断与分类治疗是提高患者生存率的关键,目前临床采用雌激素受体(ER)、孕激素受体(PR)、表皮生长因子受体2(HER2)、细胞角蛋白5/6(CK5/6)、表皮生长因子受体(EGFR)和核抗原Ki67联合进行乳腺癌分类,应用TMN分期指导临床治疗。然而,不同亚型患者的疾病进程、病理机制及治疗手段不尽相同,传统方法在疾病早期诊断和分类治疗方面存在局限性。随着诊断技术的发展,人们对乳腺癌的生物学特征有了更深入的认识,根据基因表达谱的差异,可将乳腺癌分为Lum A型(ER+或PR+、HER2-)、Lum B型(ER+或PR+、HER2+)、HER2高表达型(ER-、HER2+)、基底细胞样型和正常细胞样型,这为乳腺癌的精准分型和治疗提供了重要基础。     

上皮细胞黏附分子表达与乳腺癌病理分型及预后的相关性分析

目的分析乳腺癌患者体内上皮细胞黏附因子(EpCAM)的表达情况及其与患者临床病理分型和预后的联系。方法应用MaxVision法对776例患者体内的EpCAM表达情况进行检测,并结合患者的病理分型和预后情况进行统计学分析。结果不同淋巴结转移、肿瘤大小、人表皮生长因子受体-2(HER2)的表达和临床分期的乳腺癌患者EpCAM的表达阳性率比较,差异有统计学意义(P0.05);单因素COX分析显示,EpCAM阳性表达的患者预后较差,具体相关的分型为三阴型、腺腔B型(HER2+)和HER2过表达型,多因素Logistic分析显示,EpCAM(+)及HER2过表达型均为影响乳腺癌患者预后的危险因素。结论 EpCAM可影响乳腺癌的发展与其分子分型,尤其对于三阴型和HER2过表达型乳腺癌患者来说可以独立影响预后,检测可针对EpCAM的分子靶点对乳腺癌进行靶向治疗。     

非小细胞肺癌罕见靶点靶向治疗最新研究进展

靶向治疗的快速发展,使非小细胞肺癌(non-small cell lung cancer, NSCLC)的治疗取得革命性突破。相较于放化疗,靶向治疗可显著提高NSCLC患者的5年生存率,改善其预后。靶向治疗针对的靶点除常见的表皮生长因子受体(epidermal growth factor receptor, EGFR)突变基因外,我国肺癌人群中还存在诸多罕见靶点,如间变性淋巴瘤激酶(anaplastic lymphoma kinase, ALK)、间质表皮转化因子(mesenchymal to epithelial transition factor, MET)、人表皮生长因子受体2(human epidermal growth factor receptor 2, HER2)等。近年来,针对这些罕见靶点的新型药物不断更新、相继进入临床使用,并取得了令人惊艳的疗效。本文对以ALK、MET、HER2为靶点的靶向治疗最新研究进展进行梳理和总结,以期为NSCLC的临床治疗提供借鉴。     

探讨不同预处理方法对HER2基因荧光原位杂交效果的影响

正人类表皮生长因子受体2基因(HER2)定位于17号染色体,编码一种具有酪氨酸激酶活性的跨膜生长因子受体。研究表明,乳腺癌HER2基因扩增或蛋白过表达与疾病进展和不良预后相关,且是靶向治疗的靶点~([1])。目前指南推荐通过免疫组化技术(IHC)检测HER2蛋白的表达,或通过原位杂交技术(ISH)检测HER2基因~([2,3])。原位杂交技术分为显色原位杂交(CISH)和荧光原位杂交(FISH)~([4])。文献对     

人表皮生长因子受体3在乳腺癌组织中的表达及临床意义

目的探讨人表皮生长因子受体(HER)3基因在乳腺癌组织中的表达及其与临床病理学特征和预后的相关性。方法采用免疫组织化学法检测126例乳腺癌组织中HER3的表达,分析其表达与患者年龄、月经情况、TNM分期、肿瘤大小、淋巴结转移、雌激素受体(ER)、孕激素受体(PR)、HER2及预后的关系。结果 (1)乳腺癌组织中HER3的阳性表达率为30.2%。HER3阳性表达在乳腺癌绝经患者中占43.3%,高于未绝经者的18.2%(P0.05);淋巴结转移阳性的乳腺癌患者HER3阳性表达率为40.0%,高于无淋巴结转移患者的21.2%,差异有统计学意义(P0.05);HER2阳性的乳腺癌患者HER3阳性表达率为42.5%,高于HER2阴性者的24.4%,差异有统计学意义(P0.05)。(2)HER3阳性患者的五年无病生存率更低(P0.05)。(3)HER3与HER2均阳性的乳腺癌患者淋巴结转移率较高(P0.05)。结论 HER3的表达可能在乳腺癌的发生和发展过程中起重要作用,并影响其预后,HER3可能成为判断乳腺癌预后的指标及临床治疗的靶点。     

三阴性乳腺癌及其研究进展

乳腺癌是一种异质性非常高的肿瘤,它在分子生物学特征、病理及免疫表型和对治疗的反应等多方面都存在着明显的差异。三阴性乳腺癌(triple negative breast carcinoma,TNBC)是指雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)和人表皮生长因子受体-2(human epidermal growth factor receptor 2,HER2)均阴性表达的乳腺癌,被     

抗人表皮生长因子受体2阳性乳腺癌靶向治疗的疗效及安全性

目的探讨抗人表皮生长因子受体2(HER2)阳性乳腺癌靶向治疗的疗效及安全性。方法 60例HER-2阳性乳腺癌患者分为对照组(EC序贯紫杉醇/多西他赛/紫杉醇脂质体化疗)和观察组(曲妥珠单抗+EC序贯紫杉醇/多西他赛/紫杉醇脂质体化疗)各30例,比较2组临床疗效及安全性。结果治疗前2组肿瘤标志物无显著差异,治疗后观察组显著优于对照组(P0.05);治疗前2组肌酸磷酸激酶、LVEF无显著差异,治疗后观察组略差于对照组(P0.05)。结论抗HER-2阳性乳腺癌靶向治疗的疗效确切且安全性较高。     

Cetuximab in non-melanoma skin cancer

Human epidermal growth factor receptor 2 (HER2) was acknowledged as an important therapeutic target in breast cancer more than 25 years ago. Subsequently, significant basic science and translational discoveries have resulted in the approval of four HER2-targeted therapies over the past 15 years. This editorial discusses future challenges regarding selection and development of treatments for HER2-positive breast cancer, which can only be met by continuing to support research efforts into the basic mechanisms by which cancer cells escape targeted therapies. Identifying specific molecular mechanisms underlying the sensitivity or resistance to each HER2-targeted agent will ultimately allow individualized therapy for each patient.     

Targeted therapies of metastatic breast cancer: Relationships with cancer stem cells

In the last years, many targeted agents have been developed for metastatic breast cancer (MBC) treatment and are being tested in clinical trials. In spite of this, apart from epidermal growth factor receptor 2 (HER2) positive subset, no significant increase in the median overall survival (OS) has been reported. Similarly to conventional chemo- and radiotherapy, the cancer stem cell theory has been evoked to explain the frustrating results often obtained with this emerging category of drugs. This review examines the results in MBC of the approved targeted therapies or those currently under evaluation in experimental studies or in clinical trials, in the light of their relationships with breast CSCs and of the efforts to circumvent the development of resistance. In the next, there is the principal need to investigate if the effects on CSCs may be used to overcome cancer resistance and it will be opportune to consider whether molecular targeted therapies should be used alone or combined with conventional therapy, or with a different target drug specific for CSCs.     

Recent advances in the HER2 targeted therapy of gastric cancer

Recent advances in molecular targeted therapies, including targeting human epidermal growth factor receptor 2(HER2), had a major forward step in the therapy for gastric cancer patients. Application of HER2-targeted therapies, in particular trastuzumab in combination with chemotherapy in metastatic HER2-positive gastric cancers, resulted in improvements in response rates, time to progression and overall survival. Nevertheless, as with breast cancer, many patients with gastric cancer develop resistance to trastuzumab. Several promising therapies are currently being developed in combination with chemotherapy to increase the efficacy and overcome the cancerresistance. Here we review the current overview of clinical application of agents targeting HER2 in gastric cancer. We also discuss the ongoing trials supporting the use of HER2-targeted agents combined with cytotoxic agents or other monoclonal antibodies.     

Use of Pertuzumab for the Treatment of HER2-Positive Metastatic Breast Cancer

Introduction

Targeting the human epidermal growth factor receptor (HER) family of tyrosine kinase receptors has proven to be effective as a therapeutic strategy for HER type 2 (HER2)-positive breast cancer. Since resistance to trastuzumab occurs relatively frequently, particularly in the metastatic setting, novel anti-HER2 targeted therapies with complementary and/or synergistic mechanisms of action have been under development. Pertuzumab, a HER2-targeted monoclonal antibody that prevents HER2 dimerisation, is the first of a class of promising targeted agents for the treatment of HER2-positive breast cancer.

Methods

A review of the biomedical literature published prior to February 2013 was conducted in English using PubMed. ClinicalTrials.gov was searched for appropriate clinical trials. The search terms used included breast neoplasm, pertuzumab, dimerisation, and HER2-positive. Abstracts of studies presented at the ASCO and ESMO Annual Meetings, and San Antonio Breast Cancer Symposium were also included.

Results

Pertuzumab represents a novel anti-HER2 targeted therapy for HER2-positive breast cancers. In this article, we describe the mechanism of action of pertuzumab, as well as its drug development process and preclinical testing results. Based on the results of ancillary studies, dual inhibition using pertuzumab and trastuzumab was shown to be effective for the management of HER2-positive metastatic breast cancers pre-treated with trastuzumab-based therapy. For the first-line setting, the combination of both pertuzumab and trastuzumab with docetaxel (CLEOPATRA trial; clinical evaluation of pertuzumab and trastuzumab) has changed the paradigm of patient management.

Conclusion

Pertuzumab provided a more comprehensive inhibition of HER2-driven signalling pathways. When administered together with trastuzumab, pertuzumab represent a significant advancement for the treatment of HER2-positive metastatic breast cancer patients.     

Anti-HER2 PLGA-PEG polymer nanoparticle containing gold nanorods and paclitaxel for laser-activated breast cancer detection and therapy

Phase-transition nanoparticles have been identified as effective theragnostic, anti-cancer agents. However, non-selective delivery of these agents results in inaccurate diagnosis and insufficient treatment. In this study, we report on the development of targeted phase-transition polymeric nanoparticles (NPs) for the imaging and treatment of breast cancer cell lines over-expressing human epidermal growth factor receptor 2 (HER2). These NPs contain a perfluorohexane liquid interior and gold nanorods (GNRs) stabilized by biodegradable and biocompatible copolymer PLGA-PEG. Water-insoluble therapeutic drug Paclitaxel (PAC) and fluorescent dye were encapsulated into the PLGA shell. The NP surfaces were conjugated to HER2-binding agent, Herceptin, to actively target HER2-positive cancer cells. We evaluated the potential of using these NPs as a photoacoustic contrast agent. The efficacy of cancer cell treatment by laser-induced vaporization and stimulated drug release were also investigated. The results showed that our synthesized PLGA-PEG-GNRs (mean diameter 285 ± 29 nm) actively targeted HER2 positive cells with high efficacy. The laser-induced vaporization caused more damage to the targeted cells versus PAC-only and negative controls. This agent may provide better diagnostic imaging and therapeutic potential than current methods for treating HER2-positive breast cancer.     

HER2 testing: a review of detection methodologies and their clinical performance

The ERBB2 proto-oncogene, commonly referred to as the human epidermal growth factor receptor-2 (HER2) gene, encodes a 185 kd receptor tyrosine kinase. Overexpression of the protein leads to constitutive activity of the HER2 receptor and breast tumor development through enhanced cell proliferation, survival, motility and adhesion. Overabundance of the HER2 receptor, typically caused by amplification of the HER2 gene, is present in approximately 10-30% of invasive breast cancers, and is associated with an aggressive disease course and decreased disease-free and overall survival in node-positive patients. Tratuzumab, a humanized murine monoclonal antibody, offers a targeted treatment modality for tumors that over express the HER2 protein. Tratuzumab, shown to be effective and initially approved for treatment of metastatic breast cancer, has recently been shown to be very effective in the adjuvant setting. Thus, to offer prognostic information and to direct appropriate treatment it is important to provide accurate laboratory assessment of the status of HER2. This article provides an overview of the methods currently used to assess HER2.     

Dual HER2 inhibition strategies in the management of treatment-refractory metastatic colorectal cancer: History and status

Human epidermal growth factor receptor 2 (HER2) signaling pathway activation has been identified as a contributor to de novo or acquired resistance to epidermal growth factor receptor (EGFR) inhibitors in a small subset of patients with metastatic colorectal cancer (mCRC). Dual anti-HER2-targeted treatment exhibits strong antitumor activity in preclinical models of HER2-positive mCRC, supporting its testing in clinical trials. The HERACLES trial at four Italian academic cancer centers has confirmed the effectiveness of dual blockage of HER2 with trastuzumab plus lapatinib in patients with heavily pretreated HER2-positive mCRC, refractory to the anti-EGFR antibodies cetuximab or panitumumab. Here, we reviewed the preclinical studies exploring the role of HER2 signaling in the development of anti-EGFR therapy resistance and discussed the status of clinical trials assessing the activity of HER2 inhibitors in this setting.     

Biomedical Applications of Trastuzumab: As a Therapeutic Agent and a Targeting Ligand

Trastuzumab (TZ) is a humanized monoclonal antibody targeted to the extracellular domain of human epidermal growth factor receptor 2 (HER2), a tyrosine kinase receptor. TZ is approved by the Food and Drug Administration (FDA) for the treatment of HER2‐overexpressing early stage and metastatic breast cancer and HER2‐overexpressing metastatic gastric cancer. For breast cancer, it is recommended as both a single agent and in combination with standard chemotherapy. In the last few years, TZ has also been used as a targeting ligand. Overexpression of HER2 in breast cancer and the presence of free surface functional groups on TZ provide an opportunity to use it as a targeting ligand. TZ can be conjugated to various nanoparticulate systems such as dendrimers, polymeric, and protein nanoparticles to target drug delivery. TZ‐conjugated inorganic nanoparticles have been reported for imaging and diagnostic purposes. This review summarizes the applications of TZ both as a therapeutic agent and as a targeting ligand.     

Update on HER-kinase-directed therapy in prostate cancer

The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases is part of a network of pathways that are involved in the development and progression of prostate cancer. HER-kinase receptors include epidermal growth factor receptor (EGFR), HER2, HER3, and HER4, which must combine as dimers to affect signaling. Different combinations of receptors produce different qualities and levels of pathway activation. Among HER-family receptors, HER2 activation is particularly important in breast cancer, as HER2 gene amplification is associated with a distinct clinical course and response to treatment with a HER2-directed therapy (trastuzumab). Although HER2 can be over-expressed in prostate cancer, there is no clinical data to support the use of trastuzumab for prostate cancer patients. Preclinical and clinical data show that the activation of the HER-kinase axis is important for the progression of prostate cancer to androgen-independent disease. Data points towards the importance of inhibiting multiple members of the HER-kinase family to achieve more complete blockade of this axis for cancers other than HER2-overexpressing breast cancer. Multiple pharmaceutical agents that block the HER-kinase axis are currently being tested for patients with prostate cancer. These include antibodies, tyrosine kinase inhibitors, and novel strategies which seek to decrease HER2 expression.