化生性乳腺癌的研究进展

化生性乳腺癌（metaplastic breast carcinoma, MBC）是一种罕见的预后较差的具有明显异源性成分的乳腺癌类型。其特点为肿块平均直径较大,较少淋巴结受侵,组织学分级较高,并且激素受体和人类表皮生长因子受体2（HER-2）阳性率较低。本文就近年来化生性乳腺癌在临床、病理、免疫组化、遗传学、诊断、治疗及预后等方面的特点作一综述。     

16例乳腺化生性癌的临床病理分析及EMT相关指标的表达

目的:研究乳腺化生性癌（metaplastic carcinoma of the breast,MBC）的临床病理特征,并探讨上皮间质转化(epithelial-mesenchymal transformation,EMT)指标E-钙黏蛋白（E-cadherin）与波形蛋白（Vimentin）在MBC和乳腺浸润性导管癌（invasive ductal carcinoma of the breast,IDC）中的差异性表达。方法:回顾性分析16例MBC患者的临床病理资料;同时选取与上述MBC临床病理特征匹配的16例IDC作为对照组。采用免疫组化SP法检测上述两组病例癌组织中ER、PR、HER-2、Ki-67、E-cadherin以及Vimentin的表达情况。结果:16例MBC中4例为纯鳞状细胞癌,4例为鳞状细胞癌伴有非特殊性浸润性癌,7例为梭形细胞癌,1例为混合型;患者中位发病年龄51岁,中位最大直径3.8 cm,淋巴结阳性率43.8%;ER/PR阳性率为0,HER-2阳性率为18.8%,13例为三阴性乳腺癌。E-cadherin在MBC组中的正常表达率低于IDC组（0% vs 37.5%,P<0.05）;Vimentin在MBC组中表达增加,强于IDC组（P<0.05）。结论:MBC是一种罕见的特殊类型的浸润性乳腺癌,形态学异质性明显,激素受体低表达,分子分型以三阴性癌为主;另外MBC中EMT程度明显高于IDC,故其预后较IDC差。     

粘液性乳腺癌的临床研究进展

粘液性乳腺癌(Mucinous breast carcinoma,MBC)是一种来自乳房的侵袭性肿瘤。其不是乳腺癌的常见类型,关于乳腺粘液性乳腺癌的文献比较少见。基于肿瘤的细胞构成,粘液性乳腺癌分为两种亚型:单纯型乳腺粘液癌(Pure mucinous breast carcinoma,PMBC)和混合型乳腺粘液癌(Mixed mucinous breast carcinoma,MMBC)。本文将对粘液性乳腺癌的临床特征、免疫表型、基因组学、鉴别诊断、治疗和预后做一综述。     

乳腺化生性癌的临床病理特征及预后影响因素*

目的:分析乳腺化生性癌（metaplastic breast carcinoma,MBC ）患者的临床病理特征及其影响预后的因素。方法:收集2005年1 月至2015年1 月55例天津医科大学肿瘤医院诊治MBC 患者完整的临床病理资料。回顾性分析MBC 患者的临床病理特征、复发及生存情况。MBC 患者根据淋巴结是否转移分为淋巴结阳性组（13例）及淋巴结阴性组（39例）;根据术后是否接受化疗、放疗及内分泌治疗,将其分为化疗组（40例）和非化疗组（15例）、放疗组（12例）及非放疗组（43例）和内分泌治疗组（5 例）及非内分泌治疗组（50例）。 并且每例MBC 患者与3 例同期年龄及临床TNM 分期情况基本类似,均接受手术治疗的三阴性乳腺癌（TNBC）患者170 例匹配。结果:MBC 患者5 年无疾病生存率（disease-free survival,DFS）和总生存率（overall survival,OS）分别为45.0% 及48.2% ,显著低于TNBC 患者5 年DFS 74.7% 及OS83.5% ,且两者之间比较5 年OS和DFS 差异具有统计学意义（均P <0.001）。 肿瘤大小、淋巴结是否转移及接受化疗与否是影响患者生存预后的重要因素。化疗组5 年OS和DFS 明显高于非化疗组的OS（P = 0.008）和DFS（P = 0.033）。 淋巴结阳性组的MBC 患者接受放疗可明显提高其5 年OS（P = 0.030）。 结论:MBC 是一种侵袭性强的罕见的乳腺癌特殊类型,预后较TNBC 差,化疗使其5 年OS及DFS 获益,且以铂类为基础的化疗方案可使患者获益更大,对淋巴结阳性患者应行术后放疗。      

化生性乳腺癌预后影响因素分析与预后模型构建

目的:分析对比中国和美国化生性乳腺癌(metaplastic breast carcinoma,MBC)患者的临床病理特征和预后影响因素,并构建列线图来预测MBC患者的3年和5年生存率。方法:以SEER数据库中提取的673例患者作为建模集,采用Cox等比例回归模型分析确定MBC的独立预后因素,然后将这些因素纳入并构建列线图模型,然后以我院的36例MBC患者作为验证集进行外部验证。结果:建模集和验证集的临床病理特征除年龄、肿瘤分级、是否第一原发肿瘤及N分期外无明显差异。单因素及多因素分析结果显示,所有患者中,年龄、是否化疗、T分期、N分期以及M分期均是MBC患者预后的独立危险因素。将这些因素纳入并建立列线图预测模型。结论:列线图能准确预测我国MBC患者的预后情况,为临床的诊疗提供科学依据。     

Snail和E-cad在化生性乳腺癌中的表达及其临床意义

【摘 要】目的 探讨化生性乳腺癌组织中Snail和上皮性钙黏附素（E-cad）的表达水平及其与临床病理特征的关系。方法 采用免疫组化SP法检测58例化生性乳腺癌组织中Snail和E-cad的表达,并收集相应病例的临床病理资料,分析Snail、E-cad表达与化生性乳腺癌临床病理特征的关系及两蛋白的相关性,同时根据随访资料分析两者表达与复发转移的关系。 结果 在化生性乳腺癌中,Snail和E-cad的阳性表达率分别为77.6％（45／58）和483％（28／58）。Snail的表达与临床分期、淋巴结转移和ER表达有关（P＜0.05）,而E-cad表达与组织学分级、淋巴结转移有关（P＜0.05）,两者与年龄、HER-2表达、病理类型、肿瘤大小及月经状态均无关（P＞0.05）。Snail与E-cad的表达呈负相关（r=-0.308,P=0.019）,且均与化生性乳腺癌复发转移有关（P＜0.05）。结论 Snail和E-cad联合检测可判断化生性乳腺癌的恶性程度和侵袭能力,且与复发转移有关,两者有望作为化生性乳腺癌治疗的分子靶点。     

男性乳腺包裹性乳头状癌1例并文献复习

<正>男性乳腺癌(male breast cancer,MBC)在全部乳腺癌中的比例﹤1%^[1],其中特殊组织学类型的包裹性乳头状癌(encapsulated papillary carcinoma,EPC)在临床上更为罕见,国内仅有少量个案报道。本文报道1例男性乳腺EPC的诊治过程,结合国内外文献,总结该病的诊疗方法,旨在提高临床对MBC罕见病理类型的认识,避免误诊、误治。1病历资料患者男,73岁,因发现左侧乳腺肿物3个月住院治疗。胸部查体：左侧乳头内上方可触及一大小约3 cm×4 cm肿物,质硬,形状不规则,边界清,     

乳腺腺癌伴梭形细胞化生一例并文献复习

乳腺腺癌伴梭形细胞化生（adenocarcinoma with spindle cell metaplasia of the breast）是一种罕见类型的乳腺癌,属于乳腺化生性癌的一种亚型,肿瘤以梭形细胞为主,细胞异型性不明显,核分裂像不多,极易造成误诊。目前,对于其临床特点、治疗方式及预后都不十分清楚。南昌市第三医院乳腺诊治中心2010年10月收治了1例乳腺腺癌伴梭形细胞化生患者。将患者的临床病理特征、鉴别诊断及预后情况结合文献复习做一报告。     

乳腺髓样癌与浸润性导管癌临床病理特征和预后比较

 目的　比较乳腺髓样癌（MBC）与浸润性导管癌（IDC）的临床病理特征和预后。方法　回顾性分析经手术治疗的73例MBC和112例IDC患者的临床资料,比较两者的临床病理特征和预后。结果　IDC组腋窝淋巴结转移率为35.6 %（26／73）,较MBC组的50.9 %（57／112）低（P＝0.049）;IDC组雌激素受体（ER）、孕激素受体（PR）阳性表达分别为13.7 %（10／73）、16.4 %（12／73）较MBC组的50.0 %（56／112）、48.2 %（54／112）低（P＝0.000）;IDC组中三阴型乳腺癌比例为68.5 %（50／73）较MBC组的20.5 %（23／112）高（P＝0.000）;MBC组中乳腺X线片摄影表现更为不典型,较多表现为良性肿块（分别为30.1 %、15.2 %,P＝0.015）;MBC组、IDC组5年无瘤生存率分别为78.1 %、83.5 %,5年总生存率分别为79.8 %、84.1 %（P＝0.451、P＝0.308）。结论　超声可能为检出MBC的主要手段,MBC预后未必好于IDC,化疗在MBC治疗中的作用不可忽视。     

乳腺分泌性癌的研究进展

乳腺分泌性癌（ secretory carcinoma of the breast ）是一种发生于成人和儿童的罕见肿瘤。1966年, McDivitt和Stewart ［1］报道了一组患有该肿瘤的年轻病例,并称之为幼年型癌。然而,文献报道大多数患者并非年幼患者,而是成年患者,因此“乳腺幼年型癌”被重新命名为分泌性癌［2］。相对于其他类型的乳腺癌而言,分泌性癌有其特殊的流行病学、大体形态、组织学形态、免疫表型和遗传学特点,因此被认为是一种独立的组织学类型。2003年和2012年乳腺肿瘤病理学及遗传学分类（世界卫生组织肿瘤分类及诊断标准系列）将乳腺分泌性癌列为独立的类型,归入特殊类型的乳腺癌［3-4］。但是,有关该类型癌的组织起源仍存在争议,临床病理诊断易与其他乳腺肿瘤相混淆,年轻人与老年人预后也有所不同。本文就乳腺分泌性癌诊断与治疗的研究进展作一综述。     

乳腺浸润性导管/小叶混合癌的临床病理特征和预后分析

目的:探讨乳腺浸润性导管/小叶混合癌（IDC-L）与浸润性小叶癌（ILC）及浸润性导管癌（IDC）临床病理特征以及预后的差异。方法:回顾性分析2009年1月至2015年12月上海交通大学乳腺癌数据库中有完整临床病理资料与随访资料的IDC-L、ILC与IDC患者的临床病理特征以及预后的差异。结果:共2 957例乳腺癌患者入组,其中IDC-L、ILC与IDC分别有109、177和2 671例。多因素分析显示,与IDC-L相比,IDC患者多中心病灶和脉管浸润较少,而HER2阳性和Ki-67高表达较多（P<0.05）;ILC患者发病年龄较大、脉管浸润较少（P<0.05）。IDC-L患者的5年无乳腺癌生存率（BCFI）（82.1% vs 90.7%,P=0.040）和总生存率（OS）（91.0% vs 94.4%,P=0.029）比IDC患者差;但与ILC患者（BCFI:84.1%,P=0.803,OS:92.6%,P=0.803）无明显差异。多因素生存分析显示,病理类型、肿瘤大小、淋巴结状态以及分子分型是影响患者BCFI和OS的独立因素（P<0.05）,IDC-L较IDC患者有较差的BCFI（HR=1.67,95%CI:1.02~2.70,P=0.042）及OS（HR=1.89,95%CI:1.04~3.45,P=0.037）。结论:IDC-L临床病理特征与ILC相似,但与IDC有较多不同;IDC-L预后劣于IDC,与ILC无明显差异,有待进一步研究证实。     

乳腺黏液癌的临床病理特征和分子表型及其与预后的关系

  目的   探讨乳腺黏液癌(mucinous carcinoma, MC)的临床病理特征、分子表型及预后情况。   方法   收集天津医科大学附属肿瘤医院2004年1月至2010年12月间经手术切除、病理证实的乳腺黏液癌242例, 并随机选取同时期的乳腺浸润性导管癌(invasive ductal carcinoma, IDC)300例作为对照, 回顾性分析其临床病理资料及预后情况。   结果   乳腺单纯型黏液癌与混合型黏液癌在淋巴结转移、超声诊断准确率、p53表达及无病生存率方面差异有统计学意义(P < 0.05), 而在年龄、月经状况、家族史、肿瘤直径、总生存率方面差异无统计学意义(P > 0.05)。乳腺黏液癌与浸润性导管癌的分子分型、总生存率、无病生存率差异有统计学意义(P < 0.05)。   结论   乳腺黏液癌预后较好, 单纯型黏液癌与混合型黏液癌有不同的临床病理特征及预后, 对乳腺黏液癌进行亚型分型对指导临床治疗及预测预后有重要意义。      

Invasive lobular breast cancer: A review of pathogenesis,diagnosis, management,and future directions of early stage disease

Invasive lobular carcinoma (ILC) is the second most common type of invasive breast cancer after invasive ductal carcinoma (IDC). Invasive lobular carcinoma has unique clinical, pathologic, and radiographic features which suggest that it is a distinct clinical entity; however, it is treated with the same treatment paradigms as IDC. Information regarding the specific treatment of ILC, including response to standard therapy, is sparse. Neoadjuvant treatment considerations are of great importance in this space as ILC is often found at a locally advanced stage. In this review, we summarize the classic features of ILC and the available data regarding efficacy of both endocrine therapy and chemotherapy in curative treatment of breast cancer.     

Current Progress in the Treatment of Metaplastic Breast Carcinoma

Metaplastic breast cancer (MBC) is a rare type of breast carcinoma, characterized by various combinationsof mesenchymal, adenocarcinoma and other epithelial components. MBC often manifests as a large mass, withlow axillary lymph node involvement and poor prognosis. Knowledge and treatment patterns about MBCdemographics, presentation and tumor characteristics are very limited. In clinical practice, MBC is usuallytreated based on the guidelines developed for infiltrating ductal carcinoma (IDC). The ideal treatment paradigmfor MBC is unknown due to its low incidence and pathological variability, so potential predictors of treatmentefficacy need to be explored. This review summarizes the current models and strategies for MBC according tothe published literature.     

Medullary breast carcinoma

More then half a million cases each year makes breast cancer the most common malignancy in female. Medullary breast carcinoma (MBC) is a type of invasive ductal breast carcinoma that usually has favorable prognosis and is characterized by the high graded structure, high mitotic rate and heavy lymphoid infiltration. The last feature makes MBC an attractive subject for detailed studies in respect to development of novel immunological approaches for cancer treatment. In this review we have summarized the data on MBC morphology, antigenic repertoire and molecular biology features. The aim of this review was to illuminate the unique biological features and to outline theoretical basis for further investigations of MBC.     

乳腺黏液癌的MRI表现及与临床病理特征相关性分析

目的:探讨分析乳腺黏液癌（mucinous breast carcinoma,MBC）的MRI影像学特征及临床病理特征。方法:收集2010年1月至2016年12月间临床资料完整的乳腺黏液癌患者75例,其中单纯型乳腺黏液癌（Pure MBC）患者54例,混合型乳腺黏液癌（Mixed MBC）患者21例。分析比较两组患者的MRI影像学表现和临床病理特征。结果:在两组乳腺癌患者中,单纯型乳腺黏液癌与混合型乳腺黏液癌比较,混合型乳腺黏液癌更多表现为淋巴结阳性(P=0.002);在年龄、月经状况、家族史、雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER2）水平方面差异无统计学意义（P<0.05）;在MRI检查方面,肿块平均大小及肿块边缘、形态、强化方式、强化程度及表观弥散系数(ADC)差异具有统计学意义(P<0.001)。结论:了解乳腺黏液癌的MRI影像学及临床病理特征,可帮助临床医师预测乳腺黏液癌及其亚型和患者的预后,有利于制定最优的治疗方案。     

超声特征联合免疫组化对不同组织学分级的乳腺浸润性导管癌的诊断价值

目的:评估乳腺浸润性导管癌（invasive ductal cancer,IDC）的超声特征及免疫组化生物分子的表达在不同组织学分级中的鉴别诊断价值。方法:回顾性分析2017年05月至2019年05月经三家医院收集的390例IDC患者,均接受超声检查及免疫组化检查,并且均经穿刺或手术病理结果证实;分析超声特征及免疫组化生物分子在不同组织学分级IDC之间的差异。结果:不同组织学分级的IDC中,肿瘤方位、回声、微钙化、血流分级表现具有显著统计学差异;ER、HER-2、Ki-67、AR、p53表达水平具有显著统计学差异;根据主成分分析计算得出的综合评分绘制受试者工作特征曲线（receiver operating characteristic curve,ROC）,得出IDC I级与Ⅱ、Ⅲ级的AUC、灵敏度、特异度分别是0.611、0.818、0.409,Ⅰ、Ⅱ级与Ⅲ级的AUC、灵敏度、特异度分别是0.596、0.558、0.675。结论:超声特征结合免疫组化生物分子一定程度上可以预测IDC的组织学分级,为临床医师在决策患者的治疗方案中提供一定的指导。     

Comparison of the Characteristics of Medullary Breast Carcinoma and Invasive Ductal Carcinoma

Purpose

Medullary breast carcinomas (MBC) have been known to represent a rare breast cancer subtype associated with a more favorable prognosis than invasive ductal carcinomas (IDC). The purpose of this study was to compare the clinicopathologic characteristics and outcomes of MBC with those of IDC.

Methods

We retrospectively reviewed medical records of patients with invasive breast cancer who were managed surgically from August 1995 to June 2010.

Results

Fifty-two patients were identified with MBC and 5,716 patients were identified with IDC. The clinicopathologic features, disease-free survival (DFS), and overall survival (OS) of patients with MBC were compared with those of patients with IDC. The MBC group presented at a younger age (p=0.005) and had a significant association with a higher histological grade (p=0.003) and nuclear grade (p<0.001) as well as negative estrogen receptor (p<0.001) and progesterone receptor (p<0.001) status. Lymphatic invasion was absent (p<0.001) and lymph node metastasis was rare (p<0.001). The DFS and OS did not differ significantly between the two groups (5-year DFS: 88.0% vs. 89.2%, p=0.920; 5-year OS: 93.4% vs. 94.4%, p=0.503). In multivariate analysis, the factors associated with DFS and OS were nuclear grade, histological grade, tumor size, lymph node metastasis, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status, chemotherapy, and hormone therapy. However, DFS and OS were not significantly different between IDC and MBC according to histological type itself (DFS: hazard ratio 0.85, 95% confidence interval 0.12-6.05, p=0.866; OS: hazard ratio 1.49, 95% confidence interval 0.21-10.77, p=0.692).

Conclusion

Although MBC has specific clinicopathologic features, its prognosis does not differ from IDC and is determined by prognostic factors such as tumor size and lymph node metastasis. Therefore, patients with MBC also require the same intensive treatment provided for IDC.     

Medullary carcinoma of the breast. Prevalence and prognostic importance of classical risk factors in breast cancer

In an earlier study of 235 breast cancers with medullary features, we concluded from a multivariate Cox regression analysis that only four histopathological features contained significantly positive prognostic information. In the present study, continuing our work on the same population base, we used these histological characteristics (predominantly syncytial growth pattern, no tubular component, diffuse stromal infiltration with mononuclear cells and sparse necrosis (< 25%), as diagnostic criteria for medullary carcinoma of the breast (MC). We found a significantly better prognosis for patients with MC than those with non-medullary carcinoma (NMC) or infiltrating ductal carcinoma (IDC). All tumours in the MC group were grade II or III (96% grade III). A significantly different distribution of general risk factors such as lymph node status, invasion, steroid receptor status, and menopausal status, was found between the group of MC and the control group of IDC grades II + III. Further, general risk factors, which are found to be of major prognostic importance in IDC, had little prognostic impact in MC. We found MC to be biologically unique, and patients with MC have a better than average prognosis compared to that of IDC. We propose a new histological definition of MC, but stress that prospective studies have to be performed.