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。      

三阴乳腺癌的临床病理特征和预后分析

背景与目的:三阴性乳腺癌(triple negative breast cancer,TNBC)是一类高危乳腺癌,其雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone,PR)和入表皮生长因子受体2(human epidermal growth factor receptor-2.Her-2)表达均为阴性,因而不能从针对激素受体的内分泌治疗和Her-2的靶向治疗中获益.本研究旨在分析TNBC患者的临床病理特征、生存情况和预后影响因素.方法:收集免疫组织化学检测ER、PR和Her-2均为阴性的128例乳腺癌患者的临床病理资料,观察其长期生存情况.结果:所有患者中,浸润性导管癌占89.0%.T1、T2患者占78.1%,有淋巴结转移的患者占48.4%,Ⅰ、Ⅱ期患者占60.9%.5年无病生存率、无局部复发生存率、无远处转移生存率和总生存率分别为71.1%、84.3%、75.8%和83.6%.单因素分析结果显示,淋巴结转移、肿块大小、分期和脉管癌栓与TNBC预后有关.多因素分析显示,淋巴结转移(RR=17.449,P=0.000)、原发肿块大小(RR=31.237,P=0.000)是影响TNBC预后的因素.结论:TNBC有明显不同的临床病理特征,发病时常年轻、有淋巴结转移、肿块较大,有乳腺癌家族史,预后差,淋巴结转移和肿块大小是影响TNBC预后的因素.     

三阴性乳腺癌与人表皮生长因子受体2过表达乳腺癌患者的临床病理特征和预后比较

目的 研究三阴性乳腺癌和人表皮生长因子受体2(Her-2)过表达乳腺癌患者的临床病理学特征以及无病生存期.方法 对1998至2003年间在上海长海医院确诊的770例乳腺癌患者进行回顾性分析,确立三阴性乳腺癌表型,并且与Her-2过表达乳腺癌进行比较,分析两组患者p53和上皮性钙黏蛋白(E-cadherin)状态以及发病年龄、肿瘤直径、肿瘤部位、组织学类型、分级、淋巴结转移状态、AJCC分期、是否化疗和手术方式之间的差异.对影响两组患者尤病生存率的相关因素进行分析.结果 770例患者中,三阴性乳腺癌96例,占12.5%;Her-2过表达乳腺癌164例,占21.3%.三阴性乳腺癌和Her-2过表达乳腺癌的p53和E-cadherin状态的差异均无统计学意义(均P>0.05).三阴性乳腺癌(71.9%)较Her-2过表达乳腺癌(58.5%)更容易发生淋巴结转移(P=0.034),并且三阴性乳腺癌中淋巴结转移≥10枚患者所占的比例(26.0%)明显大于Her-2过表达乳腺癌(12.2%,P=0.034).三阴性乳腺癌中组织学分级为3级的患者比例(67.7%)明显高于Her-2过表达乳腺癌(42.1%,P<0.0001).三阴性乳腺癌的肿瘤直径与淋巴结转移状态有关(P=0.024).三阴性乳腺癌和Her-2过表达乳腺癌的局部复发率和远处转移率的差异虽无统计学意义(P>0.05),但三阴性乳腺癌的无病生存期(61.85个月)明显短于Her-2过表达乳腺癌(78.69个月,P=0.047).结论 与Her-2过表达乳腺癌比较,三阴性乳腺癌的侵袭性更强,患者的无病生存期更短,预后更差.     

激素受体和人表皮生长因子受体2的表达与改良根治术后淋巴结阳性乳腺癌患者预后的关系

目的 探讨雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(Her-2)的表达情况与行改良根治术后腋窝淋巴结阳性乳腺癌患者预后的关系.方法 收集835例行改良根治术后腋窝淋巴结阳性乳腺癌患者的临床和随访资料.根据ER、PR和Her-2的免疫组化检查结果,将患者分为Rec-/Her-2-(三阴性)组、Rec-/Her-2+组、Rec+/Her-2+组和Rec+/Her-2-组,比较其局部区域复发率、远处转移率、无瘤生存率和总生存率.结果 835例患者中,三阴性组141例,Rec-/Her-2+组99例,Rec+/Her-2+组157例,Rec+/Her-2-组438例.Rec+/Her-2-患者的5年局部区域复发率为6.2%,低于其他患者(12.9%,P=0.004).与受体阳性组(Rec+/Her-2+和Rec+/Her-2-)比较,受体阴性组(Rec-/Her-2-和Rec-/Her-2+)有较高的5年远处转移率(26.4%和19.7%,P=0.0008)、较低的5年无瘤生存率(66.7%和75.6%,P=0.0001)和较低的5年总生存率(71.4%和84.2%.P=0.0000).多因素Cox回归分析结果显示,激素受体和Her-2的表达状态是乳腺癌患者局部区域复发、远处转移、无瘤生存和总生存的独立影响因素(均P<0.05),Rec+/Her-2-患者的局部区域复发风险低,受体阴性患者发生远处转移和死亡的风险高.结论 ER、PR和Her-2是改良根治术后腋窝淋巴结阳性乳腺癌患者的独立预后因素.     

激素受体双阴性HER-2过表达乳腺癌的临床病理特征及预后分析

目的 探讨雌激素受体(ER)和孕激素受体(PR)双阴性、HER-2过表达乳腺癌患者的发病情况、临床病理特征及预后影响因素.方法 回顾性分析1999年3月至2004年12月间,经免疫组化检测ER和PR双阴性、HER-2过表达乳腺癌患者的临床资料,分析其临床病理特征、分子生物学指标、治疗方式及其对预后的影响.结果 111例ER和PR双阴性、HER-2过表达的乳腺癌患者,中位发病年龄49岁.浸润性导管癌97例(87.4%),腋窝淋巴结转移54例(48.6%),Ⅰ、Ⅱ、Ⅲ期患者分别为25例(22.5%)、44例(39.6%)和36例(32.4%).5年无病生存率和总生存率分别为70.7%和73.1%.单因素分析结果显示,原发肿瘤大小(P=0.000)、淋巴结转移状态(P=0.000)、分期(P=0.003)及有无曲妥珠单抗治疗(P=0.000)是预后影响因素.多因素分析结果显示,淋巴结转移状态(P=0.002)和原发肿瘤大小(P=0.012)是独立预后影响因素.结论 ER和PR受体双阴性、HER-2过表达的乳腺癌是一种特殊亚型乳腺癌,具有较差的临床生物学特征,淋巴结转移数和原发肿瘤大小是独立的预后影响因素.     

5758例女性乳腺癌激素受体状态及其相关因素分析

目的 探讨中国女性乳腺癌激素受体状态特点.方法 回顾性分析5758例女性乳腺癌患者的临床病理资料.结果 5758例患者中,雌激素受体(ER)阳性3692例,阳性率为64.1%;孕激素受体(PR)阳性4044例,阳性率为70.2%.单因素分析结果显示,女性乳腺癌的ER状态与患者的年龄、月经状态、T分期、N分期、腋窝淋巴结转移、组织学类型、组织分化程度有关,PR状态与患者的T分期、N分期、腋窝淋巴结转移、组织学类型、组织分化程度有关(均P＜0.05).Logistic多因素回归分析结果 显示,月经状态、T分期、N分期和组织分化程度是女性乳腺癌ER状态的独立影响因素,T分期、N分期和组织分化程度是女性乳腺癌PR状态的独立影响因素.结论 中国乳腺癌ER受体阳性率低于欧美等高发地区.女性乳腺癌的ER状态与月经状态、T分期、N分期和组织分化程度有关,PR状态与T分期、N分期和组织分化程度有关.     

G蛋白偶联雌激素受体mRNA表达与乳腺癌患者临床病理特征及预后的关系

目的基于癌症和肿瘤基因图谱(TCGA)和Kaplan-Meier Plotter数据库探讨G蛋白偶联雌激素受体(GPER)mRNA在乳腺癌组织中的表达及其与预后的关系。 方法本回顾性研究利用基因表达谱交互分析(GEPIA)工具下载含有乳腺癌患者GPER mRNA二代测序数据及临床病理资料的TCGA数据集,GPER mRNA表达为偏态分布数据,用[M(P₂₅ ～P₇₅ )]表示,采用Wilcoxon W检验分析1 085例乳腺癌组织样本和291例正常乳腺组织样本GPER mRNA表达的差异,同时用Kruskal-Wallis H检验分析乳腺癌组织中GPER mRNA表达与其临床病理特征的关系,两两比较用Bonferroni-Dunn检验。利用Kaplan-Meier Plotter数据库收集共3 951例乳腺癌患者的GPER mRNA表达情况,根据GPER mRNA表达的上下四分位数确定最佳截点值(103),从而将其分为GPER高、低表达2组,进而绘制无复发生存曲线,使用log-rank检验比较GPER高表达与低表达组的无复发生存率差异。 结果正常乳腺组织中GPER mRNA表达为6.247 9(6.022 4～6.554 6),乳腺癌组织中为5.700 4(5.357 6～6.022 0),差异有统计学意义(Z＝－7.338,P<0.001)。不同T分期、N分期的乳腺癌组织中GPER mRNA表达比较,差异无统计学意义(χ²＝3.343、6.084,P＝0.488、0.193)。GPER mRNA在basal-like型、HER-2型、luminal型中的表达分别为－0.239 3(－0.250 7～－0.126 1)、－0.263 9(－0.275 9～－0.225 7)、－0.188 3(－0.239 7～－0.101 9),差异有统计学意义(χ²＝106.187, P<0.001)。两两比较发现,HER-2型与basal-like型、HER-2型与luminal型、basal-like型与luminal型相比,GPER mRNA表达的差异均有统计学意义(P＝0.019,P均<0.001)。GPER mRNA低表达患者的无复发生存率明显低于高表达患者(HR＝0.67,95%CI：0.59～0.75,P<0.001)。 结论GPER mRNA低表达患者预后更差,提示GPER可能成为乳腺癌患者预后的独立预测因子。     

5758例女性乳腺癌激素受体状态及其相关因素分析

Objective To analyze the characteristics of hormone receptor status in Chinese females with breast cancer.Methods The clinicopathalogieal data of 5758 female breast cancer patients surgically treated in our breast caneer center from Jan.1997 to Oct.2008 were retrospectively analyzed.Results The positive rates of estrogen receptor(ER)and progesterone receptor(PR)were 64.1% and 70.2%,repeetively.The ER positive rate was significantly higher in elderly,post-menopausal females with a smaller tumor and well-differentiated histology(P ＜ 0.05),while the PR positive rate was significantly correlated with only histological differentiation and tumor size(P ＜ 0.05).The ER and PR positive rates were significantly higher in the patients with lymph node metastasis than that in those without(P ＜0.05).Multivariate analysis showed that the histological differentiation,T stage,N stage and menopause status were significantly correlated with ER positive rate,while histological differentiation,T stage and N stage were significantly correlated with PR positive rate.Conclusion Our results show that the ER positive rate of breast cancer in Chinese women is lower than that in western high incidence areas.The ER positive rate is signifieandy correlated with age,histological differentiation,tumor size,and menopause status.The PR positive rate is correlated only with histological differentiation and tumor size.Interestingly,the ER and PR positive rates are significantly higher in the patients with axillary lymph node metastases than that in those without.However,further study is needed to verify this special phenomenon.     

雌激素相关标志在乳腺癌中的表达及其预后意义

用一组雌激素相关标志对５４例女性乳腺癌进行回顾性研究。患者平均４７．９岁，５年生存率为８１．５％。癌肿长径平均３．４ｃｍ，浸润性导管癌４９例，Ⅲ级３６例。肿瘤大小、组织学类型、分级与预后关系不明显。ＥＲ阳性率５５．６％，ＰＲ阳性率３８．９％，与组织蛋白酶Ｄ有较好相关性。组织蛋白酶Ｄ在癌细胞的阳性率为２７．８％，间质巨噬细胞阳性率为１００％，与ＥＲ、ＰＲ关系较密切，并与预后相关。     

乳腺癌肝转移的临床病程与预后分析

目的 探讨乳腺癌肝转移的临床病程、治疗效果及预后因素。方法 采用SPSS 11.5统计软件对152例乳腺癌肝转移患者的生存及预后因素进行回顾性分析。结果 全组中位无病生存期（DFS）为21个月,转移后中位生存期（MSR）为16个月,中位至疾病进展时间（TTP）为7．4个月。肝转移后一线化疗的有效率为54．5％,高于介入治疗（37．7％,P=0．039）。含紫杉类方案化疗组的有效率为63．3％,高于不含紫杉类方案化疗组（40．O％,P=0．04）;含紫杉类方案化疗组的TTP为10个月,亦高于不含紫杉类方案化疗组（7个月,P=0．048）。无论介入治疗（TACE）,还是化疗,治疗有效者的MSR（18个月）均长于无效者（14个月,P=0．002）。对于单发肝转移瘤患者,单纯介入治疗的MSR（30个月）长于单纯化疗（16个月,P=0．0052）;对于多发肝转移瘤患者,单纯介入治疗与单纯化疗的MSR差异无统计学意义。原发肿瘤大小、腋窝淋巴结转移数、雌激素受体状态、肝转移后转氨酶异常程度、肝转移灶大小是影响预后的重要因素。结论 有效的化疗（尤其是含紫杉类方案化疗）和介入治疗能明显改善乳腺癌肝转移患者的预后。     

乳腺癌肿瘤组织不同部位雌孕激素受体的表达

目的 探讨乳腺浸润性导管癌肿瘤组织中不同部位雌、孕激素受体表达情况.方法 收集32例手术切除乳腺浸润性导管癌肿瘤标本,于每例肿瘤标本4个不同部位取材,用免疫组化方法检测各部位雌、孕激素受体表达情况.结果 肿瘤组织不同部位雌、孕激素受体检测结果一致性好,最好Kappa值分别为0.789和0.810,最差Kappa值分别为...     

Clinical impact of assay of estrogen receptor beta cx in breast cancer

Since 1996 when estrogen receptor beta(ER beta) was discovered, much effort has been devoted to the question of the value of ER beta as a prognostic and/or predictive factor in breast cancer and its potential as a novel target for pharmacological intervention. When estrogen receptors are applied on sucrose gradients and quantified by ligand binding, we found that in contrast to ER alpha, which has a narrow tissue distribution, ER beta is expressed in many tissues including both normal and malignant breast tissue. Receptor protein levels in tissues can also be measured from the intensities of bands after Western blotting and can be quantified when purified and quantified receptor is used as a standard. With this technique, we found that there were some tumors which had over 600 fmol/mg of ER beta protein but no detectable estradiol binding. In such tumors, RT-PCR analysis revealed that ER beta cx is the only ER beta isoform present. ER beta cx is a splice variant which utilizes an alternative exon 8. This change in the C-terminus results in very poor binding to estradiol (E2) and has a dominant negative effect on ER alpha function. Immunohistochemical analysis with an ER beta cx specific antibody in 115 ER alpha-positive breast cancers revealed that about half of the samples expressed ER beta cx protein. Initial analysis of samples from patients with preoperative tamoxifen treatment revealed that ER alpha-positive tumors expressing ER beta cx and lacking PR seemed to be resistant to the anti-estrogen. We conclude that, in order to better characterize breast cancers and design appropriate therapy for individual patients, assays for ER beta cx must be made available to clinicians.     

ER和PR及Her-2对改良根治术后腋窝淋巴结阳性乳腺癌放疗疗效的影响

目的 根据ER、PR和Her-2的免疫组化检查结果,把改良根治术后的高危乳腺癌患者分为不同亚组,了解放疗对不同亚组患者的作用.方法 回顾分析437例改良根治术后病理为浸润癌的乳腺癌患者资料,分期为T3-4N1或N2-3期,有ER、PR和Her-2的免疫组化检查结果.408例接受了化疗,352例接受了放疗.ER+或(和)PR+定义为受体阳性(Rec+),ER-和PR-定义和受体阴性(Rec-),Her-2++或+++定义为Her-2阳性(Her-2+).根据结果分为Rec-/Her-2-(69例)、Rec-/Her-2+(62例)、Rec+/Her-2+(89例)和Rec+/Her-2-(217例)组,分别分析4个组在放疗和未放疗下局部区域复发率(LRR)、远处转移率(DM)、无瘤生存率(DFS)和总生存率(OS)的差别.复发率和生存率计算用Kaplan-Meier法,差异检验用Logrank法.结果 中位随访48个月,除外5例放疗不详的患者,资料齐全可分析患者432例.放疗降低了4个组患者的5年LRR,Rec-/Her-2-、Rec-/Her-2+、Rec+/Her-2+和Rec+/Her-2-组放疗和未放疗的5年LRR分别为13.1%和33.3%、9.3%和21.2%、9.7%和47.0%、3.2%和15.4%;对Rec-/Her-2-、Rec-/Her-2+和Rec+/Her-2+患者,放疗降低了5年DM,放疗和未放疗患者的5年DM分别为26.7%和49.2%、27.6%和67.5%、18.4%和100%,并提高5年DFS和OS,三组患者放疗和未放疗的5年DFS分别为66.7%和33.3%、67.7%和33.3%、72.6%和0%,三组患者放疗和未放疗的5年OS分别为73.9%和25.2%、69.8%和41.5%、91.0%和32.8%.结论 不同ER、PR、Her-2状态的改良根治术后高危乳腺癌患者均能从术后放疗中获益.     

可手术的不同分子亚型乳腺癌的临床特征和生存分析

目的 分析Luminal A型、Luminal B型、人表皮生长因子受体2(HER-2)型和Basal-like型4种乳腺癌亚型的临床特征和生存状况,探讨乳腺癌个体化综合治疗的理论基础.方法 回顾性分析经手术治疗、资料完整、免疫组化方法能明确判定受体状况的乳腺癌患者408例,比较各型乳腺癌的临床特征、复发转移及生存情况.结果 Luminal A型248例,占60.8%;Luminal B型32例,占7.8%;HER-2型51例,占12.5%;Basal-like型77例,占18.9%.HER-2型乳腺癌≤45岁者明显少于其他亚型,Basal-like型乳腺痛发生腋窝淋巴结转移者的比例低于其他亚型,Luminal B型晚期病例多于其他亚型,而HER-2型早期病例多于其他亚型.获得随访的243例患者中,复发或转移58例,死亡51例.Luminal A型的复发转移率明显低于Luminal B型和Basal-like型(均P<0.05).Luminal A型、Luminal B型、HER-2型和Basal-like型的5年生存率分别为89.83%、86.15%、86.70%和79.85%,Luminal A型高于Basal-like型(P=0.008).Luminal A型、Luminal B型、HER-2型和Basal-like型的5年无病生存率分别为83.52%、68.88%、75.83%和71.66%,Luminal A型高于Luminal B型和Basal-like型(P=0.0481和P=0.0306).结论 中国人各亚型乳腺癌的构成比与欧美国家接近,Luminal A型是最常见的乳腺癌亚型,预后较好,Basal-like型和Luminal B型所占比例较小,但预后较差.     

Relation of serum levels of estrogen and dehydroepiandrosterone sulfate to hormone receptor status among postmenopausal women with breast cancer

Background: It is hypothesized that breast cancer may consist of heterogeneous diseases with different hormonal environments classified by hormone receptor status. Epidemiologic studies evaluating risk factors for breast cancer by hormone receptor status have supported the hypothesis. However, there are inconsistencies in the risk factor profiles by estrogen receptor (ER) and progesterone receptor (PR) across the studies. To clarify the heterogeneity of the disease, it is necessary to understand not only risk factor profiles but also the biologic characteristics such as the relationships among endogenous sex hormone levels and hormone receptors. Methods: We measured serum levels of estrone (E1), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) in 142 postmenopausal women aged 50 and over with primary breast cancer who had undergone surgical treatment, and investigated the heterogeneity in the relations of endogenous sex hormone levels to hormone receptor status, using the case-series study method. Subjects were categorized into 3 classes based on tertiles of each hormone level in receptor-negative subjects, and odds ratios (ORs) for receptor-positive status compared with receptor-negative status were computed, taking the lowest category as a reference category. Results: There were clear trends toward higher serum levels of E1, E2, and DHEAS in women with PR+ cancer. The case-series approach revealed that PR+ status might be strongly associated with serum sex hormone levels. In particular, the OR of PR+ was large for a high DHEAS level (OR for the highest category = 4.28). No significant association between serum hormone levels and ER status was observed. Conclusion: The association of serum sex hormone levels with hormone receptor status may differ by PR status, but not by ER status. This finding suggests that PR status may be related to the heterogeneity in hormonal environments associated with breast cancer risk.     

Intake of fruits, and vegetables in relation to breast cancer risk by hormone receptor status

Summary The inconsistent associations between fruit and vegetable intake and breast cancer risk may be due to heterogeneity of associations by estrogen (ER) and progesterone receptor (PR) status of the tumors. We evaluated this hypothesis in a large (2,386 cases and 2,503 controls) population-based case-control study in Poland, conducted between 2000 and 2003. We observed significant associations between reduced overall risk of breast cancer and increasing levels of total fruit intake (odds ratio (OR) for highest versus lowest quartile = 0.76, 95%CI = 0.63–0.91; p-trend = 0.01), but not for total vegetable intake (1.13 (0.93–1.37), p-trend = 0.25), after controlling for age, energy intake and known risk factors for breast cancer. The inverse association with total fruit intake was stronger for risk of ER+ (0.69 (0.54–0.88), p-trend = 0.01) than ER− tumors (0.89 (0.67–1.19), p-trend = 0.57) (p-heterogeneity = 0.02). In conclusion, this study suggests that fruit intake might have differential associations for breast tumor subtypes defined by ER status.