HER-2阳性乳腺癌中肿瘤浸润淋巴细胞与雄激素受体的相关性研究

  目的  探讨人表皮生长因子受体-2（human epidermal growth factor receptor-2，HER-2）阳性乳腺癌中肿瘤浸润淋巴细胞（tumor-infiltrating lymphocytes，TILs）浸润水平与雄激素受体（androgen receptor，AR）表达的关系。  方法  收集2018年3月至2018年11月天津医科大学肿瘤医院收治的448例HER-2阳性乳腺癌患者的临床资料。病理评估TILs浸润水平，免疫组织化学方法检测AR表达情况，分析TILs浸润水平和AR表达与临床病理学参数的关系以及TILs和AR的相关性。  结果  448例HER-2阳性乳腺癌患者中TILs无浸润或低浸润的患者占38.2%（171/448）、中等浸润者占42.2%（189/448）、高浸润者占19.6%（88/448），AR阳性率为62.7%（281/448）。Spearman等级相关分析显示TILs浸润水平与AR表达呈负相关（r=-0.140，P=0.003）。在雌激素受体（estrogen receptor，ER）阳性乳腺癌中，TILs浸润水平和AR表达密切相关（P=0.009）。  结论  HER-2阳性乳腺中TILs浸润水平和AR表达呈负相关，提示HER-2阳性乳腺癌患者可根据TILs的不同浸润水平与AR的表达行精准治疗。      

ER PR 单阳性表达乳腺癌患者临床病理特征和预后分析*

目的:探讨不同的ER、PR表达对原发性侵袭性乳腺癌患者预后的影响,重点研究ER+/PR- 和ER-/PR+ 单阳性表型肿瘤的临床病理特征和预后差异。方法:回顾性分析1998年10月至2004年5 月间天津医科大学附属肿瘤医院收治的1 054 例原发性侵袭性乳腺癌患者的病例资料及随访结果,比较不同的ER、PR表达乳腺癌患者的临床病理特征和预后,明确ER+/PR- 和ER-/PR+ 单阳性表型肿瘤之间存在的差异。计算生存率采用Kaplan-Meier 方法,生存率比较应用Log-rank 检验。经COX多因素分析得出独立的预后影响因素。结果:ER+/PR- 表型肿瘤易出现于年长、绝经后的女性,肿瘤直径较小,组织分化程度较高。生存分析显示:ER+/PR+ 组预后优于ER-/PR- 组（OS:P=0.000,DFS :P=0.000）,ER或PR单阳组预后介于ER+/PR+ 组和ER-/PR- 组之间。相对于ER-/PR- 表型肿瘤,ER+/PR- 的生存优势强于ER-/PR+ ,ER+/PR- 的无瘤生存优于ER-/PR+（P=0.035）,而两者之间总体生存无明显差异（P=0.890）。 不同的ER、PR阳性表达是影响乳腺癌患者内分泌治疗的无瘤生存的独立因素（P=0.023）。 结论:ER+/PR- 和ER-/PR+ 是两种临床病理特征和预后完全不同的乳腺癌,ER-/PR+ 肿瘤表现的侵袭性行为更强,应该采取更为积极的治疗措施。ER-/PR+ 表型乳腺癌可能具有独特的生物学特征。      

乳腺癌中BAG-1 EGFR和PARP-1的表达及其临床意义

  目的  观察乳腺癌组织芯片中BAG-1、EGFR和PARP-1的表达及其与临床病理指标的相关性,并探讨其临床意义。  方法  采用免疫组织化学法对159例组织芯片中乳腺癌和癌旁组织点行BAG-l、EGFR及PARP-1蛋白检测,同时分析其与临床病理指标的相关性。  结果  乳腺癌组织中BAG-1、EGFR、PARP-1蛋白表达水平显著高于癌旁组织（P < 0.05）。BAG-1蛋白表达水平与年龄、肿瘤部位、淋巴结转移数目、临床分期均无明显相关性,但与肿瘤大小、组织学分级、ER、PR和HER-2表达以及分子分型有关（P < 0.05）;EGFR蛋白表达水平与肿瘤大小、临床分期以及分子分型有明显相关性（P < 0.05）;PARP-1与组织学分级、淋巴结转移数目、ER表达以及分子分型有关（P < 0.05）。119例病例中BAG-1蛋白表达与EGFR、PARP-1蛋白表达无明显相关性,但在三阴性乳腺癌（TNBC）中BAG-1蛋白表达与PARP-1蛋白表达呈正相关（P < 0.05）。单因素分析结果显示,BAG-1、PARP-1蛋白表达和分子分型是影响乳腺癌患者预后的因素。多因素分析结果显示,BAG-1、PARP-1蛋白表达是影响乳腺癌患者预后的独立危险因素。  结论  乳腺癌中BAG-1、EGFR和PARP-1蛋白高表达提示其可能参与乳腺癌的发生发展,BAG-1、EGFR和PARP-1高表达可作为乳腺癌诊治和预后的生物指标。      

双侧原发性乳腺癌两癌间隔时间对ER PR HER-2表达一致性及预后的影响

  目的  分析两癌发生间隔时间对双侧原发性乳腺癌雌激素受体(ER)、孕激素受体(PR)及人表皮生长因子受体2(HER-2)表达一致性及预后的影响。  方法  回顾性分析366例双侧原发性乳腺癌(bilateral primarv breast cancer, BPBC)患者的病理资料, 按照两癌发生的间隔时间进行分组, 侧重分析不同组内第一原发癌与第二原发癌ER、PR、HER-2表达的一致性及两癌间隔时间对BPBC预后的影响。  结果  BPBC第一原发癌与第二原发癌的ER、PR、HER-2表达呈正相关, 两癌间隔时间≤12个月的BPBC双侧ER、PR、HER-2表达密切相关(P < 0.05), 而两癌间隔时间 > 12个月的BPBC双侧ER、PR、HER-2表达相关性无统计学意义(P > 0.05)两癌间隔时间≤12个月较 > 12个月发生者远期生存率低, 预后差。  结论  12个月内发生的BPBC两癌在ER、PR、HER-2表达方面具有较高的相似性, 远期生存率较低, 同异时性BPBC以12个月划分更能反映两癌之间的联系及预后。      

北京市住院女性浸润性乳腺癌HER-2受体状态特征分析

目的:探讨北京市住院女性浸润性乳腺癌人表皮生长因子受体-2(HER-2)状态特点以及与临床病理因素的相关性.方法:回顾性分析中国医学科学院肿瘤医院外科1997-03-2008-10收治的5 326例女性浸润性乳腺癌患者资料,HER-2采用免疫组化法检测, + + +定义为HER-2过表达.结果:全组HER-2过表达率为16.4%.雌激素受体(ER)阳性组HER-2过表达率为10.8%,阴性组为26.4%,P<0.001;孕激素受体(PR)阳性组过表达率为13.1%,阴性组为24.1%,P<0.001;单因素分析显示,组织学分化差、腋窝淋巴转移、肿瘤体积较大、病期较晚和年轻患者中HER-2过表达率较高,P＜0.05;多因素分析显示,ER、PR状况和组织学分化程度是影响HER-2表达的独立因素.结论:HER-2过表达者肿瘤侵袭性较强、病期较晚,HER-2过表达与多种因素有关.     

原发性乳腺癌组织中雄激素受体的表达及其与临床病理指标的关系

目的探讨雄激素受体（AR）在原发性乳腺癌组织中的表达情况及其与乳腺癌临床病理指标的关系。方法采用免疫组织化学方法检测520例原发性乳腺癌患者肿瘤组织中AR、ER、PR、HER-2、Ki-67的表达情况,并结合患者年龄、月经状态,淋巴结转移情况、肿瘤大小、病理类型、TNM分期以及肿瘤组织学分级等临床病理指标进行分析。结果乳腺癌组织中AR的阳性率为81.3%,肿瘤越小者AR的阳性表达率越高（P=0.000）,组织学分级越低者AR的阳性表达率越高（P=0.029）,ER、PR阳性表达越强者AR的阳性率越高（P=0.000,P=0.000）。AR的表达与年龄、淋巴结转移、病理类型、脉管瘤栓、TNM分期、HER-2及Ki-67等无关。结论AR在乳腺癌组织中广泛表达,是乳腺癌恶性程度低、预后良好的指标;对AR阳性患者有望通过针对AR的途径来给予治疗。     

乳腺癌干细胞激素受体与HER-2表达生物学意义的分析

目的:探讨雌激素受体(ER)、孕激素受体(PR)和人类表皮生长因子受体2(HER-2)在乳腺癌干细胞(BCSCs)和其分化细胞中的表达及意义。方法:选取乳腺浸润性导管癌新鲜标本30例,采用机械分离法将乳腺癌组织块制备成单细胞悬液,通过免疫磁珠两步法从中分离出BCSCs(CD44+CD24-/low细胞)和乳腺癌分化细胞(CD24+细胞和CD44-CD24-细胞),应用免疫细胞化学Envision二步法检测两组细胞ER、PR和HER-2的表达情况。结果:BCSCs ER-表达率为83.3%(25/30),分化细胞ER-表达率为53.3%(16/30),两者差异有统计学意义,P=0.025;BCSCs PR-表达率为76.7%(23/30),分化细胞PR-表达率为23.3%(7/30),两者差异有统计学意义,P=0.000;BCSCs HER-2-表达率为83.3%(25/30),分化细胞HER-2-表达率为53.3%(16/30),两者差异有统计学意义,P=0.025;BCSCs和分化细胞表型构成不同(P=0.000),BCSCs以ER-、PR-及HER-2-表型为主,占66.7%(20/30),乳腺癌分化细胞以ER和(或)PR+、HER-2-表型为主,占43.3%(13/30)。结论:BCSCs ER、PR和HER-2均可呈现阳性或阴性表达,但以阴性表达为主,随着BCSCs的分化,其阳性表达率明显升高。BCSCs的表型以ER-、PR-及HER-2-为主,这可能是部分患者内分泌治疗失败的主要原因。     

新辅助化疗联合双靶治疗HER-2阳性乳腺癌的有效性比较

  目的  比较多西他赛+卡铂+曲妥珠单抗+帕妥珠单抗（TCbHP）、多西他赛+曲妥珠单抗+帕妥珠单抗（THP）与蒽环类+环磷酰胺序贯紫杉类+曲妥珠单抗+帕妥珠单抗（AC-THP）作为新辅助治疗方案对HER-2阳性激素受体（hormone receptor,HR）阳性和HER-2阳性HR阴性乳腺癌患者的有效性。  方法  回顾性分析2019年6月至2022年12月于天津医科大学肿瘤医院就诊的408例HER-2阳性且行标准新辅助治疗的乳腺癌患者的临床病理资料,根据HR状态分为HER-2阳性HR阳性组 211例、HER-2阳性HR阴性组197例。根据不同新辅助治疗方案进一步分为TCbHP、THP和AC-THP组,分别比较各组患者行各治疗方案的病理学完全缓解（pathological complete response,pCR）率 。  结果  HER-2阳性HR阳性乳腺癌患者中,TCbHP、THP和AC-THP组的pCR率分别为43.1%（69/160）、36.0%（9/25）和 38.5%（10/26）,各组间比较差异无统计学意义（χ²=0.580,P=0.748）;HER-2阳性HR阴性患者中,TCbHP、THP和AC-THP组的pCR率分别为85.5%（94/110）、57.3%（43/75） 和 66.7%（8/12）,TCbHP组与THP组比较差异具有统计学意义（χ²=19.967,P<0.001）。  结论  TCbHP、THP和AC-THP新辅助治疗方案对HER-2阳性HR阳性乳腺癌患者的疗效相似,TCbHP作为新辅助治疗对HER-2阳性HR阴性乳腺癌疗效更优。     

雄激素受体在非特殊类型浸润性乳腺癌中的表达及预后意义的探讨

目的∶通过免疫组化检测雄激素受体（andmgen rcpur,AR）在非特殊类型浸润性乳腺癌中的表达情况,分析AR与非特殊类型浸润性乳腺癌临床病理特征的关系,探讨AR与非特殊类型浸润性乳腺癌患者预后之间的关系,为临床医生判断预后提供参考。方法∶收集2017年1月至2019 年6月在本院经病理诊断为非特殊类型浸润性乳腺癌的病例2为例,统计其临床资料,采用Envisiom 两步法检测AR雌激素受体（erwgn repa,ER）、孕激素受体（pogeerone receptor,PR）、人表皮生长因子受体-2（humn eridrmal gowth factor rcptu-2,HER2）以及细胞增殖标记抗原 Ki67的表达情况,分析 AR与非特殊类型浸润性乳腺癌的不同组织学分级、分子分型及 Ki67之间的关系。结果;279 例非特殊类型浸润性乳腺癌中组织学分级1级6例（2.15%）,Ⅱ级217例（77.78%）,Ⅲ级 44 例（15.77%）;分子分型Luminal A型46例（16.49%）,LuminlB型153例（54.84%）,HER2 过表达型24例（8.60%）,三阴性型37例（3.26%）。AR的总阳性率为64.87%（181/279）,在组织学I级（83.33%）和Ⅱ级（68.66%）中的阳性率比在Ⅲ级（45.45%）中高（P=0.008）;AR在Luminal A型（71.74%）、LumimlB型（68.63%）和HER2过表达型（62.50%）中的阳性率高于三阴性型（27.02%）乳腺癌（P<0.001）。ER 阳性表达组的AR 阳性率（73.71%）高于ER阴性表达组（44.71%）,差异有统计学意义（P<0.001）;PR 阳性表达组（71.07%）高于 PR 阴性表达组（50.00%）,差异有统计学意义（P=0.001）。Ki-67阴性表达组的非特殊类型浸润性乳腺癌中AR 阳性率（7.45%）高于Ki-67阳性表达组（59.71%）（P=0.002）。结论∶AR的表达状态可能是乳腺癌预后的指标之一,高表达者可能预后更好。     

不同病理亚型乳腺癌脑转移患者预后分析

目的:了解不同病理亚型乳腺癌脑转移患者的预后特点。方法:根据肿瘤组织免疫组化ER、PR、HER-2 的表达情况将89例患者分为4 组:Luminal A型（ER+ 和/或PR+ ,HER-2-）17例、Luminal B型（ER+ 和/或PR+ ,HER-2 +）15例、HER-2 + 型（ER- ,PR- ,HER-2 +）24例和Basal-like型（ER- ,PR- ,HER-2-）33例。主要观察4 组患者分布比例、发病年龄、月经状态、病理类型、病理分级、肿瘤大小、淋巴结状态及脑转移发生距手术时间及部位等。使用SPSS15.0 统计软件进行数据分析,定量资料采用t检验,计数资料比较采用卡方检验,生存率计算采用Kaplan-Meier 法并用Log-rank 检验,P<0.05为差异有统计学意义。结果:所有患者当中Basal-like型所占比例最高（37.1%）,其次为HER-2 +（27%）,Luminal A型（19.1%）,Luminal B型最少（16.9%）。 Basal-like 型患者预后最差,其病理分级Ⅲ级的患者比例达到了73% 。在其他部位出现转移情况上,Luminal型患者表现出较高的骨转移倾向。全组患者的中位生存期为47个月,无病生存期为20个月,确诊脑转移后的生存期为9 个月。ER（-）且PR（-）较ER/PR（+）（45个月vs.52个月,P=0.006）、HER-2（+）较HER-2（-）（45个月vs.51.5 个月,P=0.04）、Basal-like亚型的患者预后较其他亚型差（33个月vs.52个月,P=0.000）。 结论:病理亚型是判断乳腺癌脑转移患者预后不同的良好指标,ER（-）且PR（-）、HER-2（+）、Basal-like亚型患者容易出现脑转移且预后较差。      

Androgen receptor as a target for the treatment of hormone receptor-negative breast cancer: an unchartered territory

Estrogen receptor-negative (ER-) and progesterone receptor-negative (PR-) breast cancers represent approximately 30% of all breast cancers and, in general, have a more aggressive clinical course. They are unresponsive to antiestrogens, more likely to be poorly differentiated, of higher histological grade and are associated with a higher recurrence rate and decreased overall survival. Androgen receptor (AR) expression has been reported in over 70% of breast cancer and in 45-50% of patients with ER-negative breast cancer. There is emerging evidence that the androgen signaling pathway plays a critical role in breast carcinogenesis, independent of ER. Preclinical data have suggested the inhibitory role of adrenal steroids, such as dehydroepiandosterone (DHEA) and its sulfate on the growth of human ER-negative breast cancer cell lines, when these demonstrate a strong expression of AR. This potentially results in decreased AR gene expression. However, DHEA has been shown to stimulate growth in breast cancer cells when an ER is expressed in ER-positive breast cancer cells. Therefore, the effect of adrenal steroids may differ based on the tumor hormone receptor status and ER-/PR- breast tumors may not be truly hormone 'insensitive'. Exploration of new androgen-based hormonal therapy is warranted in this patient population. This article reviews the role of the AR in breast cancer and discusses potential avenues for the treatment of ER-/PR-/AR+ tumors with 'hormonal therapy'.     

Androgen receptor expression is significantly associated with better outcomes in estrogen receptor-positive breast cancers

BackgroundThe objective of the study was to evaluate the implications of androgen receptor (AR) in breast cancers.Patients and methodsWe investigated immunohistochemical AR expression from the tissue microarrays of 931 patients between 1999 and 2005, and analyzed demographics and outcomes using uni-/multivariate analyses. Tumors with ≥10% nuclear-stained cells were considered positive for AR.ResultsAR was expressed in 58.1% of patients. AR was significantly related to older age at diagnosis, smaller size, well-differentiated tumors, higher positivity of hormone receptors, non-triple-negative breast cancers (non-TNBCs), and lower proliferative index. In estrogen receptor (ER)-negative tumors, AR was distinctively associated with human epidermal growth factor receptor type 2 (HER2) overexpression. With a mean follow-up of 72.7 months, AR was positively related to survival in ER-positive but not in ER-negative tumors. In Cox’s models, AR was an independent prognostic factor for disease-free survival in ER-positive cancers. Interestingly, molecular apocrine tumors (ER negative and AR positive) with HER2 positive status showed trends of poorer outcome, but AR had no impact on survival in patients with TNBC.ConclusionsAR is significantly associated with favorable features in breast cancers and related to better outcomes in ER-positive not in ER-negative tumors. These results suggest that AR could be an additional marker for endocrine responsiveness in ER-positive cancers and a candidate for therapeutic targeting of ER-negative tumors.     

Observations on the presence of E domain variants of estrogen receptor-alpha in the breast tumors

BACKGROUND AND OBJECTIVES: Estrogen receptor-alpha (ER-alpha) that exists as multiple splice variants, has been widely used as a prognostic marker in the management of breast cancer. Here we have analyzed the hormone binding E domain splice variants of ER-alpha in the breast tumors with reference to the immunoreactive receptor. METHODS: Thirty breast cancer patients undergoing surgery at the All India Institute of Medical Sciences, New Delhi, were analyzed for the splice variants of E domain by RT-PCR. The ER level was determined by ELISA and the samples were considered positive if the receptor levels were >or= 15 fmol/mg protein. RESULTS: Our results show that exon 4 and 5 deletions were prevalent in both ER-positive and ER-negative categories. While most ER-positive cases expressed wild-type (wt) exon 6 + 7, nearly 40% of ER-negative cases showed deletion of exon 6 + 7. Therefore, deletion of exon 6 + 7 or masking of epitopes could lead to underestimation of ER by ELISA. All the metastasis and recurrence cases had undetectable levels of ER. A significant number of node-positive cases expressed immunoreactive ER and wt exon 6 + 7 (r = 0.509, P < 0.37). CONCLUSIONS: Estimation of ER levels combined with composite analysis of ER variants may be a better prognostic marker for breast cancer.     

基于SEER数据库的乳腺黏液腺癌临床病理学特征及生存分析

背景与目的：乳腺黏液腺癌（mucinous carcinoma,MC）恶性程度较低,预后较好。目前美国国立综合癌症网络 （National Comprehensive Cancer Network,NCCN）指南推荐对雌激素受体（estrogen receptor,ER）和孕激素受体（progesterone receptor,PR）阴性MC的辅助化疗按照非特殊类型的浸润性导管癌（invasive ductal carcinoma,IDC）处理,即激素受体阴性、淋巴结阴性的pT≥0.6 cm的MC考虑及需要辅助化疗。探讨IDC和MC的临床、病理学等因素与乳腺癌特异生存率（breast cancer-specific survival,BCSS）的关系,为MC的辅助治疗策略提供依据。方法：回顾性分析2000—2009年美国流行病监测与最终治疗结果（Surveillance, Epidemiology, and End Results,SEER）数据库中可手术的245 235例IDC及6 705例MC的病例资料,比较两种不同组织学类型乳腺癌的临床病理学特征及BCSS率的差异。结果：MC患者ER阳性率高达97.3%,而IDC为76.0%（P<0.01）;中位随访104个月,整体上MC的预后优于IDC,MC的10年BCSS率为92.0%,而IDC为84.0%（P<0.001）;ER和PR均阳性的MC和IDC的10年BCSS率分别为93.0%和87.0%（P<0.001）,ER和PR均阴性则分别为81.0%和76.0%（P=0.022）;激素受体阴性的MC患者中,pT ₂ N ₀ M ₀ 和pT _3-4 N ₀ M ₀ 的BCSS率均较低,分别为85.2%和80.0%,而pT ₁ N ₀ M ₀ 预后较好,10年BCSS率为94.5%,其中接受化疗和未经过化疗的10年BCSS率分别为94.1%和94.6%（P=0.87）。结论：MC生物学行为较好,与IDC相比,MC具有更好的长期生存;激素受体阴性、pT ₁ N ₀ M ₀ 的MC预后好,辅助化疗并没有进一步改善生存,提示对这部分高选择的患者有可能豁免辅助化疗,减少不必要的毒性。     

IQGAP1在乳腺癌中的表达及意义

  目的  探讨IQGAP1（IQ motif containing GTPase activating protein 1）在乳腺癌组织中的表达及意义。  方法  采用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶（S-P法）染色法检测IQGAP1在乳腺癌组织及癌旁组织各110例中的蛋白表达水平。在正常乳腺上皮细胞系MCF-10A和乳腺癌细胞系MCF-7中开展IQGAP1表达调控实验。  结果  IQGAP1在乳腺癌组织中的表达高于癌旁正常乳腺组织（P=4.23×10-6）。IQGAP1的表达与浸润性导管癌的肿瘤大小（P=0.006）相关,在肿瘤>2 cm组明显高于肿瘤≤2 cm组。未发现与淋巴结转移（P=0.870）,临床分期（P=0.278）,ER状态（P=0.412）和PR状态（P=0.248）相关。IQGAP1高表达与乳腺癌术后无病生存时间（P=0.008）和总生存时间（P=0.029）相关。在乳腺癌细胞系MCF-7中,IQGAP1降低导致细胞增殖活性显著下降。  结论  IQGAP1可能在乳腺癌的发生发展过程中发挥重要作用。      

AMACR Expression is a Potential Diagnostic Marker in Apocrine Lesions of Breast,and is Associated with High Histologic Grade and Lymph Node Metastases in Some Invasive Apocrine Breast Cancers

BackgroundCarcinoma with apocrine differentiation (AC) is a subtype of breast carcinoma with apocrine features in >90% of the tumor. Molecular studies demonstrate AC has high expression of androgen receptor (AR) mRNA. Pure AC lack estrogen receptor (ER), progesterone receptor (PR), and express AR, with variable human epidermal growth factor 2 (HER2) status. Currently, in triple negative AC, no targetable therapies or specific diagnostic markers exist.Materials and Methodsα-Methylacyl CoA racemase (AMACR) expression was investigated as a marker of apocrine differentiation using a single-plex immunoperoxidase stain, and a novel AMACR/p63 dual stain in a subset of cases, across 1) benign apocrine lesions (apocrine metaplasia, adenosis) 2) apocrine DCIS (ADCIS), 3) AC/ invasive ductal carcinoma (IDC) with apocrine features, 4) non-apocrine triple negative breast cancer (TNBC) and 5) IDC, no special type. A sub-set of cases were evaluated by tissue microarray.ResultsAMACR expression was increased in both AC and ADCIS, with minimal expression in benign breast tissue, TNBC and IDC, NST cases. In invasive cases, those with positive AMACR (>5% positivity) were significantly associated with higher histologic grade (P = .006), initial N stage (chi squared 0.044), and lack of ER or PR expression (both P < .001), with no correlation with overall survival. Analysis of TCGA breast cancer datasets revealed AMACR expression was significantly higher in molecularly defined apocrine carcinomas relative to basal and luminal subtypes. Moreover, high AMACR expression predicted worse relapse-free and distant-metastasis free survival, among both ER-/PR-/Her2- and ER-/PR-/Her2+ breast cancer cohorts (log-rank P = .081 and .00011, respectively).ConclusionAMACR represents a promising diagnostic and prognostic marker in apocrine breast lesions. Further study is needed to determine the biologic and clinical significance of this protein in AC.     

In vivo magnetic resonance imaging of the estrogen receptor in an orthotopic model of human breast cancer

Histologic overexpression of the estrogen receptor α (ER) is a well-established prognostic marker in breast cancer. Noninvasive imaging techniques that could detect ER overexpression would be useful in a variety of settings where patients' biopsies are problematic to obtain. This study focused on developing, by in vivo MRI, strategies to measure the level of ER expression in an orthotopic mouse model of human breast cancer. Specifically, novel ER-targeted contrast agents based on pyridine-tetra-acetate-Gd(III) chelate (PTA-Gd) conjugated to 17β-estradiol (EPTA-Gd) or to tamoxifen (TPTA-Gd) were examined in ER-positive or ER-negative tumors. Detection of specific interactions of EPTA-Gd with ER were documented that could differentiate ER-positive and ER-negative tumors. In vivo competition experiments confirmed that the enhanced detection capability of EPTA-Gd was based specifically on ER targeting. In contrast, PTA-Gd acted as an extracellular probe that enhanced ER detection similarly in either tumor type, confirming a similar vascular perfusion efficiency in ER-positive and ER-negative tumors in the model. Finally, TPTA-Gd accumulated selectively in muscle and could not preferentially identify ER-positive tumors. Together, these results define a novel MRI probe that can permit selective noninvasive imaging of ER-positive tumors in vivo.