宫颈癌中表皮生长因子受体的表达与临床预后的相关性研究

目的 研究表皮生长因子受体(EGFR)在宫颈癌及宫颈上皮内瘤样病变(CIN)中的表达,并探讨其与宫颈癌发生、浸润转移及预后的相互关系.方法 应用免疫组化法对100例宫颈癌、60例CIN及40例正常宫颈上皮组织中的EGFR进行检测.结果 正常上皮、CIN、宫颈癌组织的EGFR过表达率分别为O%(0/40)、51.67%(31/60)、78.00%(78/100).宫颈癌组的EGFR过表达率显著高于CIN组(P<0.05,OR=3.32,95%CI∶1.67～6.63),2组的EGFR过表达率均显著高于对照组(P均<0.01).EGFR过表达与宫颈癌临床分期、肿瘤体积、病理类型、组织分化、宫颈浸润深度、颈管侵犯及淋巴结转移均无显著相关(P均>0.05),与宫颈癌预后也无显著相关(P>0.05).结论在宫颈癌变过程中,EGFR过度表达水平随着宫颈病变程度的加重而上升,提示EGFR过度表达与宫颈肿瘤的发生相关,EGFR可能成为有价值的宫颈癌生物学指标.EGFR过度表达与宫颈癌临床病理特征及预后无关.     

表皮生长因子受体在早期胃癌中的表达

本文采用ＡＢＣ免疫组化方法，检测了３９例早期胃癌中表皮生长因子受体的分布。发现表皮生长因子受体在正常胃粘膜中几乎不存在，而在早期胃癌和癌旁不典型增生胃粘膜中的阳性百分比（５１．２８％和４８．７２％）没有显著性差异，在印戒细胞癌和低分化腺癌中，表皮生长因子受体的阳性百分比显著高于高分化腺癌和中分化腺癌。提示表皮生长因子受体的过度表达与早期胃癌的生物学行为有一定正相关。     

Expression of transforming growth factor alpha and epidermal growth factor receptor in human bladder cancer.

We analysed the expression of epidermal growth factor receptor (EGFr) and transforming growth factor alpha (TGF-alpha) in human bladder tumours. Tumour biopsies were obtained from 54 patients with primary bladder cancer (18 stage T1 and 36 stage T2-4). The protein and mRNA expression of EGFr and TGF-alpha were quantified by ELISA and competitive RT-PCR, respectively. The EGFr protein level was significantly increased in T2-4 tumours (0.44 x 10(-11); 0.0-27.5 x 10(-11) mol/g) compared with T1 tumours (0.0; 0.0-2.0 x 10(-11) mol/g) (median; range; 2p<0.01). The EGFr protein and mRNA level correlated (Spearman r=0.45, 2p<0.005, n=40). Co-expression of TGF-alpha protein and EGFr protein was significantly associated with muscle invasive tumours (T2-4) (chi-squared=7.9, df=3, p<0.05) and the TGF-alpha protein level correlated significantly with EGFr protein expression (Spearman r=0.56, 2p<0.0001, n=54). While tumour stage correlated with survival, no correlation was observed between survival and the expression of EGFr and/or TGF-alpha. In conclusion, human bladder tumours express both EGFr and TGF-alpha. The expression of EGFr and TGF-alpha are closely correlated, and the expression of EGFr and co-expression of EGFr and TGF-alpha correlate with tumour stage.     

血管内皮生长因子及环氧合酶-2在子宫内膜腺癌中表达及意义

目的探讨血管内皮生长因子（vascular endothelial growth factor,VEGF）和环氧合酶-2（cyclooxygenase-2,COX-2）在子宫内膜腺癌中表达及临床意义。方法萎缩性正常子宫内膜患者12例（对照组）,子宫内膜增生症患者14例（子宫内膜增生组）,子宫内膜腺癌患者30例（子宫内膜腺癌组）,3组均手术切除子宫内膜组织标本,采用RT-PCR法检测子宫内膜组织COX-2及VEGF mRNA相对表达量。结果子宫内膜腺癌组、子宫内膜增生组、对照组中COX-2mRNA相对表达量分别为（133.58±56.96）%、（56.68±41.75）%、（8.33±5.21）%,VEGF mRNA相对表达量分别为（143.28±59.86）%、（57.33±46.78）%、（15.31±10.86）%,各组间COX-2mRNA及VEGF mRNA相对表达量比较差异有统计学意义（P〈0.01）;子宫内膜腺癌组COX-2表达与VEGF表达呈正相关（r=0.289,P=0.014）。结论COX-2及VEGF在子宫内膜腺癌中均呈高表达,其作为肿瘤恶化程度标记物可为临床诊疗工作提供参考依据。     

表皮生长因子受体和雄激素受体在前列腺增生及其前列腺癌组织中的表达

目的:前列腺增生症和前列腺癌病因未完全阐明,观察表皮生长因子受体和雄激素受体在前列腺增生和前列腺癌变病理组织中的表达情况,探讨两种受体在前列腺发病中的作用。方法:实验于2004-09/11在沈阳医学院病理教研室完成。选择中国医科大学手术切除并经病理证实的前列腺增生症标本45块,前列腺癌标本30块及正常前列腺组织标本中12块。应用免疫组织化学SP法检测标本组织中表皮生长因子受体和雄激素受体表达情况(表达强度为0～,>为强阳性,阳性表达强度高,为细胞分化率强)。结果:①前列腺增生和前列腺癌组织中表皮生长因子受体的阳性表达率明显高于正常组织(91%,87%,50%)。②前列腺癌中雄激素受体的表达率明显高于增生和正常组织(90%,71%,58%),而增生组织中雄激素受体强阳性率又明显高于正常组织(51%,8%)。③表皮生长因子受体与雄激素受体表达在正常组织中呈负相关(r=-0.706,P<0.05),增生组织中两者表达无相关(r=0.132,P>0.05),而癌变组织中两者表达呈正相关(r=0.578,P<0.01)。结论:在病理状态下,表皮生长因子受体与雄激素受体之间的关系没有减弱,而是进一步增加,并且其各自的强阳性率也均显著提高,表皮生长因子受体的这种超敏状态,在基质-上皮的相互作用中介导雄激素的生物学效应。表皮生长因子受体与雄激素受体之间这种相互作用的失衡对前列腺增生症和前列腺癌的发生起关键的作用。     

胃癌组织中表皮生长因子受体和环氧合酶-2的表达及其临床意义

目的 探讨表皮生长因子受体(epithelial growth factor receptor,EGFR)和环氧合酶-2(cyclooxygenase-2,COX-2)在胃癌组织中的表达及其临床意义与相互关系.方法 采用免疫组化Envision二步法检测40例胃癌组织中EGFR和COX-2的表达.结果 IEGFR表达阳性率为72.50%(29/40),COX-2阳性表达率为52.50%(21/40),二者的表达与胃癌淋巴结转移明显相关(P<0.05);②EGFR和COX-2在胃癌中的阳性表达与临床分期有关,在TNM分期中Ⅲ+Ⅳ期阳性表达率高于Ⅰ+Ⅱ期(P<0.05);③胃癌组织中COX-2表达与EGFR表达之间存在相关性(P<0.05).结论 COX-2和EGFR过度表达参与了胃癌的发生发展过程,并与其淋巴结转移和TNM分期有关;胃癌中COX-2和EGFR的表达具有正向协同性.     

两种细胞因子受体在胰腺癌中的表达及临床应用价值

目的探讨胰腺癌组织中表皮生长因子受体（EGFR）和肝细胞生长因子受体（Met）基因和蛋白的表达情况,及其与胰腺癌临床病理特征和预后的关系。方法采用免疫组化法检测78例胰腺癌组织和23例正常胰腺组织中EGFR和Met蛋白的表达情况,采用实时定量聚合酶链反应（RT-RCR）法检测 EGFR和Met-DNA的相对拷贝数。结果78例胰腺癌组织中,EGFR和Met蛋白的阳性表达率明显高于正常胰腺组织,差异均有统计学意义（ P＜0．05）。肿瘤直径大于4 cm患者、胰腺癌组织高中分化患者、出现远处转移患者、淋巴转移患者、肠系膜上血管侵犯患者、T N M分期为Ⅲ和Ⅳ期患者中EG FR和M et蛋白的表达均明显高于肿瘤直径小于或等于4 cm患者,胰腺癌组织低分化患者,未出现远处转移患者、未有淋巴转移患者、未出现肠系膜上血管侵犯患者、TNM 分期为Ⅰ和Ⅱ期患者,差异具有统计学意义（P＜0．05）。胰腺癌患者中,EGFR和Met-DNA 相对拷贝数均明显高于正常胰腺组织中EGFR和Met-DNA相对拷贝数,差异具有统计学意义（P＜0．05）。高表达EGFR和Met胰腺癌患者的平均生存时间均显著低于Met及EGFR低表达患者,差异具有统计学意义（P＜0．05）。Met和EGFR均高表达的患者的平均生存时间较Met或 EGFR单一高表达者的短,差异具有统计学意义（P＜0．05）。结论 EGFR和M et的表达与胰腺癌的临床病理相关指标密切相关,对二者的分析研究有助于对胰腺癌患者的预后作出预测,并对化疗药物新靶点筛选提供理论依据。     

Alterations of human placental epidermal growth factor receptor in intrauterine growth retardation.

We studied human placental microvillous EGF receptor (EGFR) and its relationship with maternal and placental features in 14 cases of intrauterine growth retardation. Placental EGFR phosphorylation was significantly decreased or absent in 12 cases of small for gestational age neonates, as shown by SDS-PAGE, autoradiography, and scanning analysis. Specific [125I]EGF binding and Scatchard plots of the binding data showed a decreased number of EGFR in 6 of the 12 cases, with a mean maximal binding capacity of 1.09 +/- 0.32 pmol/mg for high affinity sites (mean control value = 2.30 +/- 0.23 pmol/mg). Most of the hypertensive women and smokers belonged to this subgroup. In three of the remaining six cases of small gestational age placentas with low EGFR phosphorylation, there was no maternal pathology or significant parenchymatous placental lesions. Five showed a 175-kD EGFR species when probed by [125I]EGF cross-linking and Western blotting with RK2 and C-Term, two polyclonal anti-EGFR antibodies, suggesting abnormal transduction of the EGF-induced signal. The sixth placenta yielded a single 145-kD EGFR band consistent with an abnormal EGFR structure; Western blot analysis showed no immunoreactive band. In conclusion, maternal and placental pathologies in intrauterine growth retardation are associated with various alterations of placental EGFR, pointing out the importance of EGFR ligands in the regulatory pathway of placental and fetal growth.     

Correlation between microRNA-21, microRNA-206 and estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 in breast cancer

BackgroundAlthough the function of microRNA-21 and microRNA-206 in breast cancer cells have been investigated in vitro, their association with estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are not reported.MethodsER, PR, HER2, and Ki-67 staining pattern were utilized to classify 75 breast cancer patients recruited. The malignancy was predicted with tumor nodes metastases (TNM) classification. RT-qPCR was performed to detect the relative expression of ER, PR, and HER2 in tumor samples and microRNA-21 and microRNA-206 in the serum. Spearman's correlation analysis was used to determine the association between different molecules. According to the staining pattern, the breast cancer patients were classified into five types.ResultsmicroRNA-21 was up-regulated in HER2 positive and Basal-like breast cancer types, while microRNA-206 was up-regulated in Luminal A and B types of breast cancer. microRNA-21 expression negatively correlated with the level of ER and PR but positively correlated with HER2 expression and tumor malignancy, while microRNA-206 showed the opposite trend. Neither microRNA-21 nor microRNA-206 showed any significant correlation with the age of the patients.ConclusionBoth microRNA-21 and microRNA-206 closely correlate with ER, PR, and HER2 expression, which can be considered as clinical biomarkers.     

Effects of the epidermal growth factor receptor inhibitor OSI-774, Tarceva,on downstream signaling pathways and apoptosis in human pancreatic adenocarcinoma

Pancreatic cancer is the fifth leading cause of cancer death in North America. Gemcitabine improves the quality of life of patients but fails to significantly reduce mortality. Our laboratory has demonstrated previously that the phosphatidylinositol 3'-kinase inhibitor wortmannin promotes gemcitabine antitumor activity (S. S. W. Ng et al., Clin. Cancer Res., 7: 3269-3275, 2001). The present study examined the effects of the epidermal growth factor receptor (EGFR) inhibitor OSI-774 ("Tarceva") alone and in combination with wortmannin and/or gemcitabine on downstream signaling molecules, as well as apoptosis in primary pancreatic cancer xenografts implanted orthotopically in severely combined immunodeficient mice. Tumors established from two pancreatic cancer patients [Ontario Cancer Institute Pancreas number (OCIP#) 2 and OCIP#7] were treated with various combinations of the above three drugs and harvested for analyses of the following: the levels of phosphorylated and nonphosphorylated forms of EGFR, protein kinase B (PKB/Akt) and extracellular-regulated kinase (ERK1/2), and the extent of apoptosis using immunofluorescence image analysis and TUNEL assay, respectively. OSI-774 alone significantly inhibited phosphorylation of EGFR in both of the primary xenografts. Phosphorylation of pERK decreased in OCIP#2, but not in OCIP#7. No significant effects on pPKB because of OSI-774 were observed in either tumor type. The extent of apoptosis was significantly increased by 2-fold in OCIP#2 tumors treated with gemcitabine and wortmannin in combination; an additional 2-fold increase in apoptosis was evident in the presence of OSI-774. Although wortmannin failed to enhance gemcitabine-induced apoptosis in OCIP#7 tumors, the extent of apoptosis was significantly increased with the inclusion of OSI-774 in the combination. Taken together, these findings support the use of OSI-774 plus a phosphatidylinositol 3'-kinase inhibitor in combination with gemcitabine in the treatment of pancreatic cancer.     

表皮生长因子受体在人输卵管中的表达与变化

目的:探讨表皮生长因子受体(EGFR)在人输卵管上皮组织中的表达和变化规律.方法:收集月经规律、有正常生育史的育龄妇女输卵管组织33例,绝经期妇女输卵管组织15例.育龄妇女输卵管标本取材均包括峡部、壶腹部和伞部,按月经周期分为增生早期组6例,增生中期组5例,增生晚期组5例,分泌早期组7例,分泌中期组5例和分泌晚期组5例.绝经妇女输卵管取壶腹部标本.采用免疫组织化学方法检测榆卵管组织中EGFR的表达,并应用Leica Q550图像分析系统分析阳性细胞表达强弱.结果:育龄妇女输卵管3段上皮和基质中均有EGFR蛋白表达,上皮细胞阳性表达高于基质.壶腹部和伞部上皮细胞EGFR阳性表达高于峡部,且在增生早期较低,增生中晚期和分泌早中期增高,分泌晚期下降.绝经期妇女输卵管上皮EGFR表达最低.结论:人输卵管组织中存在EGFR表达,且具有阶段性和周期性变化,推测EGFR可能参与输卵管多种生理作用.     

Chemotherapy for alpha-fetoprotein producing gastric cancers expressing human epidermal growth factor receptor 2

Although, gastric cancer is one of the most common cancers worldwide, alpha-fetoprotein (AFP) producing human epidermal growth factor receptor 2 (HER2) positive gastric cancers are rare. AFP producing gastric cancer has a poor prognosis and an appropriate treatment option has not been established to date. A 75-year-old woman with AFP- producing gastric cancer was treated with S-1, an oral fluoropyrimidine derivative, chemotherapy after distal gastrectomy. Recurrence of gastric cancer was observed after 18 months and immunohistochemistry analysis showed AFP and HER2 positive gastric cancer. The patient received combination therapy containing capecitabine, cisplatin, and trastuzumab. Computed tomography scans showed regression of the lymph node metastasis. The patient's quality of life substantially improved after the treatment. Thus, the present case suggests that AFP and HER2 positive gastric cancer can be effectively treated with, capecitabine, cisplatin, and trastuzumab combination therapy.     

Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha.

The epidermal growth factor (EGF) receptor is activated by both EGF and transforming growth factor-alpha (TGF-alpha). Using immunohistochemical and immunoblotting techniques we now report that the EGF receptor, EGF, and TGF-alpha are found in both pancreatic acini and ducts in the normal human pancreas, and that all three proteins are expressed at higher levels in human pancreatic cancer tissues. Using in situ hybridization techniques, we also report that the mRNA encoding the EGF receptor, EGF, and TGF-alpha colocalize with their respective proteins. Northern blot analysis of total RNA indicates that, by comparison with the normal pancreas, the pancreatic tumors exhibit a 3-, 15-, and 10-fold increase in the mRNA levels encoding the EGF receptor, EGF, and TGF-alpha, respectively. Furthermore, by in situ hybridization, there is a marked increase in these mRNA moieties within the tumor mass. These findings suggest that EGF and TGF-alpha may participate in the regulation of normal pancreatic exocrine function, and that overexpression of the EGF receptor and its two principal ligands may contribute to the pathophysiological processes that occur in human pancreatic cancer.     

乳腺癌ER、PR、c-erbB-2和nm23表达的相关性及临床病理意义

目的研究乳腺癌癌基因c-erbB-2、抑癌基因nm23和雌激素(ER)、孕激素受体(PR)的表达及意义。方法应用免疫组化SP法检测126例浸润性乳腺癌c-erbB-2、nm23及雌、孕激素受体的表达。结果①ER的表达与癌组织分化、肿瘤TNM分期及肿瘤大小呈负相关,小叶癌ER阳性率高于导管癌,而与患者年龄及淋巴结转移无显著相关性。②PR的表达与癌组织分化、肿瘤TNM分期呈负相关,与肿瘤大小、肿瘤类型、患者年龄及淋巴结转移无显著相关性。③c-erbB-2表达与肿瘤TNM分期、组织学分级、肿瘤大小及淋巴结转移呈正相关,与患者年龄、肿瘤类型无显著相关性。④乳腺癌Ⅰ期nm23表达的阳性率及阳性强度明显高于Ⅱ、Ⅲ期癌,nm23表达与组织学分级、淋巴结转移呈负相关,而与肿瘤大小及类型无显著相关性。⑤ER与PR表达呈正相关;nm23表达与ER、PR表达呈正相关,与c-erbB-2表达呈负相关;癌组织c-erbB-2与ER表达呈负相关,与PR表达无显著相关性。结论ER、PR、c-erbB-2及nm23的联合检测能够较好地反映乳腺癌病理生物学特征。     

免疫组化标记物在子宫内膜样腺癌与宫颈腺癌诊断中的表达及临床意义

目的探讨波形蛋白(Vim)、癌胚抗原(CEA)、雌激素受体(ER)、孕激素受体(PR)和P16蛋白等免疫组化标记物在子宫内膜样腺癌与宫颈腺癌鉴别诊断中的表达,并分析其临床意义。方法选取2013年1月至2014年6月广西壮族自治区妇幼保健院收治的子宫内膜样腺癌(A组)与宫颈腺癌(B组)患者各80例。采用免疫组化法检测Vim、CEA、ER和P16蛋白表达,并比较Vim、CEA、ER三联检测与Vim、CEA、ER和P16蛋白四联检测的各项功能指标。结果 A组的Vim和ER阳性率分别为71.25%、73.75%,均高于B组,差异均有统计学意义(P0.05);B组的CEA和P16阳性率分别为73.75%、67.50%,均高于A组,差异均有统计学意义(P0.05)。A组四联检测的特异度、敏感度及准确度分别为92.43%、56.44%、71.21%,B组分别为98.62%、58.57%、74.62%,均分别高于同组三联检测的特异度、敏感度及准确度,比较差异均有统计学意义(P0.05)。结论子宫内膜样腺癌组织Vim和ER阳性表达较高,宫颈腺癌组织CEA和P16阳性表达较高,p16蛋白联合传统三联检测可以提高子宫内膜样腺癌与宫颈腺癌鉴别诊断的准确性。     

中国人脑星形胶质细胞瘤中表皮生长因子受体的表达及其靶向治疗

背景越来越多恶性脑胶质瘤存在的基因缺陷被发现,恶性脑胶质瘤的基因治疗逐渐成为热点,胶质瘤的治疗可以靶向于脑胶质瘤的基因缺陷.目的研究中国人脑星形胶质细胞瘤中表皮生长因子受体(epidermalgrowthfactor receptor,EGFR)的表达,并探讨其临床意义.设计以金标准为依据的诊断性试验的病例观察性研究.地点、对象和干预人脑星形胶质细胞瘤新鲜手术标本37例,其中男22例,女15例,年龄11～69岁,平均37岁,均来自于1998/2000长征医院手术病例.样本包含术中所切除肿瘤组织及配对瘤周组织,按照Kernohan病理分级,分为低级别组(Ⅰ～Ⅱ级,12例)和高级别组(Ⅲ～Ⅳ级,25例).人脑胶质瘤细胞株U87MG,U251MG,大鼠脑胶质瘤细胞株C6.应用免疫组化方法(Evision-HRP法)检测人脑星形胶质瘤标本(含配对瘤周组织)和体外培养的多株人和大鼠胶质瘤细胞系的EGFR表达.主要观察指标EGFR在人星形细胞瘤、脑胶质瘤细胞株中的表达;EGFR表达与肿瘤病理分极的相关性.结果人脑星形胶质瘤组织EGFR阳性率为70%(26/37),明显高于瘤周组织(32%,12/37),差异有显著性意义(x2=10.602,P＜0.01).Ⅲ～Ⅳ级肿瘤EGFR阳性率为84%(21/25),Ⅰ～Ⅱ级为42%(5/12),高级别组肿瘤EGFR表达水平显著低于低级别组,差异有显著性意义.(x2=6.955,P＜0.01),体外实验显示不同来源细胞系间的EGFR表达率差异存在显著性意义.结论中国人脑星形胶质瘤存在EGFR的过度表达,提示EGFR可作为恶性脑胶质瘤细胞的标志物.为基因治疗提供了适宜的靶向,为研究EGFR介导的脑胶质瘤靶向性基因治疗建立基础.     

骨髓增生异常综合征表皮生长因子受体的表达及其与细胞凋亡的关系

目的　探索骨髓增生异常综合征 (MDS)造血细胞中表皮生长因子受体 (EGFR)表达及其与细胞凋亡的关系。方法　取 18例MDS患者骨髓有核细胞经离心涂片机制片 ,用免疫酶标记方法(碱性磷酸酶 抗碱性磷酸酶系统 ,APAAP)及TdT介导的dUTP缺口末端 (荧光素 )标记 (TUNEL)法先后在同一标本上检测EGFR表达和凋亡信号。 9名正常人骨髓作对照。另外 ,18例MDS中有 15例、9名正常人中有 6名经流式细胞仪分选CD3 4+细胞并制备涂片后按上述方法进行EGFR和凋亡检测 ,并分析两者间的关系。结果　①MDS骨髓细胞EGFR表达 [(38.6± 2 4.6 ) %]高于正常对照 [(18.1±14 0 ) %](P <0 .0 5 ) ;②MDS细胞凋亡主要发生在EGFR阴性细胞 (16 .1%) ,EGFR阳性细胞中凋亡细胞仅占 1.4%(P <0 .0 1) ,EGFR表达与细胞凋亡呈负相关 (r =- 0 .70 1;tr=3.6 0 ;P <0 .0 1) ;③CD3 4+细胞EGFR表达阳性率RAEB RAEB t CMML组高于RA RAS组 ,分别为 (2 0 .6± 2 7.9) %和 (8.9±11 8) %,但差异无显著性 ,细胞凋亡率RAEB RAEB t CMML组低于RA RAS组 ,分别为 (18.2± 12 5 ) %和 (4 5 .2± 2 0 .5 ) %(P <0 .0 5 )。结论　MDS造血细胞过度表达EGFR。EGFR表达增高可能预示MDS的恶性增殖倾向并通过某种途径抑制细胞凋亡。因此抗EGFR治疗有希望成为治疗MDS     

A shift in the treatment of hormone receptor and human epidermal growth factor receptor 2-positive metastatic breast cancer

Historically, postmenopausal women with estrogen receptor (ER)-positive metastatic breast cancer (MBC) with a long disease-free interval and small volume disease have received an aromatase inhibitor. However, the advent of human epidermal growth factor receptor 2 (HER2) testing and its recognition as a poor prognostic indicator has led to the first line use of anti-HER2 directed therapy in combination with chemotherapy. The optimal treatment for those who are both hormone receptor and HER2 receptor positive is less clear. Tumors rich in ER are considered to be less responsive to chemotherapy, and hormone therapy has the benefit of being less toxic than chemotherapy. However, preclinical evidence suggests that HER2 overexpression may confer resistance to endocrine therapy, even in the presence of hormone receptors, due to crosstalk between the two pathways. This review summarizes the evidence from three clinical trials for combining endocrine therapy with anti-HER2 therapy in MBC. The trials raise the possibility of a new treatment approach to co-positive tumors in patients with good performance status and low tumor burden, and a means to potentially delay the need for chemotherapy.