Clinicopathological characteristics of estrogen receptor-beta-positive human breast cancers.

Recent studies have identified the presence of estrogen receptor (ER)-beta in addition to ER-alpha in human breast cancers, but the clinicopathological characteristics of ER-beta-positive tumors remain to be established. In this study, we have conducted an immunohistochemical analysis of ER-alpha and ER-beta expression in human breast cancers. In addition, we investigated the correlation of ER-alpha and ER-beta expression with progesterone receptor (PR) status, determined by enzyme immunoassay, and with various clinicopathological factors. Of 79 tumors, 49 (62%) were positive for ER-alpha and 24 (30%) were positive for ER-beta, and there was no significant association between ER-alpha and ER-beta expression. ER-alpha-positive tumors were significantly more likely to be PR-positive than were ER-alpha-negative tumors (P < 0.0001), but there was no significant association between ER-beta expression and PR status. However, the PR values of ER-alpha-positive and ER-beta-positive tumors (65 +/- 17 fmol / mg protein, mean +/- SE) were marginally significantly lower than those of ER-alpha-positive and ER-beta-negative tumors (340 +/- 109) (P = 0.08). ER-beta positivity was significantly associated with small tumor size ( < or = 2 cm) and high histological grade (P < 0.05), and this association was also observed when only ER-alpha-positive tumors were considered. These results suggest that determination of ER-beta status might be clinically useful for further defining the characteristics of ER-alpha-positive tumors.     

三阴性乳腺癌的临床病理特点及预后分析研究

目的：探讨三阴性乳腺癌患者临床病理特点、生存率以及影响预后的因素。方法：回顾性分析30例三阴性乳腺癌患者的资料,分析其临床病理特点、免疫组化指标和各种治疗方式对生存率的影响。结果：全组30例患者均为女性,占同期收治乳腺癌患者的5.7%,中位年龄50岁（39-76岁）。其中,浸润性导管癌21例（70.0%）,单纯癌4例（13.3%）,髓样癌2例（6.7%）,管状腺癌2例（6.7%）,导管内癌1例（3.3%）。Ⅰ期患者5例（16.7%）,Ⅱ期15例（50.0%）,Ⅲ期8例（26.7%）,Ⅳ期2例（6.7%）。核分级1级4例（13.3%）,2级11例（36.7%）,3级15例（50.0%）。伴有脉管瘤栓10例（33.3%）,伴有神经浸润5例（16.7%）。中位生存时间3.8年（1.6-7.5年）。单因素分析结果显示,影响总生存的因素为肿瘤大小、淋巴结状态、临床分期、脉管瘤栓和神经浸润。多因素分析结果显示,肿瘤大小和淋巴结状态是影响预后的独立因素。3年总生存率65.7%。结论：三阴性乳腺癌发病率较低,组织学分级较高,多为浸润性导管癌,易较早出现复发和转移。影响生存率的因素为肿瘤大小、淋巴结状态、临床分期、脉管瘤栓和神经浸润,其中影响预后的独立因素是肿瘤大小和淋巴结状态。     

三阴性乳腺癌的临床病理特点及预后分析研究

目的:探讨三阴性乳腺癌患者临床病理特点、生存率以及影响预后的因素。方法:回顾性分析30例三阴性乳腺癌患者的资料,分析其临床病理特点、免疫组化指标和各种治疗方式对生存率的影响。结果:全组30例患者均为女性,占同期收治乳腺癌患者的5.7%,中位年龄50岁(39-76岁)。其中,浸润性导管癌21例(70.0%),单纯癌4例(13.3%),髓样癌2例(6.7%),管状腺癌2例(6.7%),导管内癌1例(3.3%)。Ⅰ期患者5例(16.7%),Ⅱ期15例(50.0%),Ⅲ期8例(26.7%),Ⅳ期2例(6.7%)。核分级1级4例(13.3%),2级11例(36.7%),3级15例(50.0%)。伴有脉管瘤栓10例(33.3%),伴有神经浸润5例(16.7%)。中位生存时间3.8年(1.6-7.5年)。单因素分析结果显示,影响总生存的因素为肿瘤大小、淋巴结状态、临床分期、脉管瘤栓和神经浸润。多因素分析结果显示,肿瘤大小和淋巴结状态是影响预后的独立因素。3年总生存率65.7%。结论:三阴性乳腺癌发病率较低,组织学分级较高,多为浸润性导管癌,易较早出现复发和转移。影响生存率的因素为肿瘤大小、淋巴结状态、临床分期、脉管瘤栓和神经浸润,其中影响预后的独立因素是肿瘤大小和淋巴结状态。     

年轻三阴性乳腺癌患者的临床病理特征及预后分析

目的 分析年轻三阴性乳腺癌(TNBC)患者的临床病理特征和预后因素.方法 1999年1月至2007年12月间,中国医学科学院肿瘤医院收治的年龄≤35 岁的年轻TNBC患者94例,所有患者肿瘤组织中雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(Her-2)均为阴性,收集患者的临床病理资料和生存情况,分析其临床病理特点和预后因素.结果 全组94例年轻TNBC患者,占同期收治年轻乳腺癌患者的12.0%.主要病理类型为浸润性导管癌,共81例,占86.2%.分期为Ⅰ、Ⅱ、Ⅲ和Ⅳ期的患者分别有17例(18.1%)、48例(51.1%)、28例(29.8%)和1例(1.1%).14例(14.9%)患者存在脉管瘤栓.全组94例患者的1、3、5和7年无病生存率(DFS)分别为88.3%、66.9%、59.7%和59.7%,1、3、5和7年总生存率(OS)分别为98.9%、85.6%、72.9%和69.6%.单因素预后分析结果显示,肿瘤大小、腋淋巴结状态、临床分期以及有无脉管瘤栓对年轻TNBC患者的5年OS具有显著影响(均P<0.05).多因素预后分析结果显示,有无脉管瘤栓是影响年轻TNBC患者预后的独立因素(P<0.05).在随访期出现复发和(或)转移的33 例患者中,29例发生于术后3年内,其余4例发生于术后3～4年间.结论 年轻TNBC 患者具有独特的临床、病理和预后特点,需要探索更为合理的个体化治疗方案.     

浸润性三阴性乳腺癌超声特征的临床、病理学及免疫组织化学基础

背景与目的：三阴性乳腺癌（triple-negative breast cancer,TNBC）细胞增殖程度高,有明显的肿瘤异质性,缺乏针对性治疗药物,是恶性程度最高、预后最差的乳腺癌分子分型。超声是TNBC筛查和鉴别诊断的重要影像学方法之一。TNBC的超声图像特征表现出明显的变异性。该研究旨在探讨临床、病理学及免疫组织化学因素对TNBC超声图像特征的影响。方法：回顾性分析119例手术后经病理学检查证实的浸润性TNBC患者的术前超声图像、临床及病理学资料。2名具有5年以上临床经验的超声科医师对乳腺癌肿块超声图像进行特征分析与评估,评估内容包括肿块的方位、形态、边缘、内部回声、后方回声改变及钙化。按照患者年龄、肿瘤大小、病理组织学级别、Ki-67表达水平及人类表皮生长因子受体2（human epidermal growth factor receptor-2,HER2）评分将患者分组,以研究这些因素对TNBC超声图像特征的影响。结果：浸润性TNBC的超声特征与患者年龄、肿块大小、病理学分级、Ki-67表达水平及HER2评分相关：患者年龄影响肿块的后方回声（P=0.002）,肿块大小影响肿块边缘是否毛刺成角（P=0.025）,病理学分级影响肿块的形态（P=0.008）及后方回声（P=0.044）,Ki-67表达影响肿块的形态（P=0.042）、边缘是否毛刺成角（P=0.005）及后方回声（P=0.005）,HER2评分影响钙化的发生率（P=0.024）。结论：浸润性TNBC的超声声像图特征与患者年龄、肿块大小、病理学分级、Ki-67增殖水平及HER2评分有关。了解TNBC的超声特征及变异性相关的临床、病理学及免疫组织化学基础,可辅助早期诊断和提高诊断准确性。     

Clinicopathological features of triple-negative breast cancer in Taiwanese women

Background  

The goal of this study was to identify prognostic factors that influence the survival outcome of Taiwanese women with triple-negative breast cancer (TNBC).     

Increased phosphorylation of Akt in triple-negative breast cancers

Cells from breast cancers lacking hormone receptors (estrogen receptor [ER], progesterone receptor [PgR]) and human epidermal growth factor receptor (HER) 2 strongly express the cell proliferation marker Ki-67. However, the mechanisms of and stimulus signals involved in cell proliferation of this type of breast cancer are not well understood. The aim of the present study was to examine the characteristics of signal transduction in triple-negative (ER-, PgR-, and HER2-negative) breast cancers. For 44 tumor samples, western blotting analysis was conducted to examine the phosphorylation of HER2, external signal-regulated kinase (ERK)1 and -2 and Akt, and the immunohistochemical phenotypes of the samples with respect to ER and HER2 were also assessed. Phosphorylation of HER2 was detected in 4 of 15 immunohistochemically HER2-positive tumor samples (26.7%). ERK1/2 was more highly phosphorylated in triple-negative breast cancers. Phosphorylation of Akt kinase was significantly higher in triple-negative breast cancers. Triple-negative breast cancers are characterized by increased phosphorylation of Akt kinase. In the present study, we found for the first time that there is a population with a significantly activated Akt pathway in this type of breast cancer. ( Cancer Sci 2007; 98: 1889–1892)     

Clinicopathological features and treatment strategy for triple-negative breast cancer

Breast cancers are divided into at least 4 subtypes on the basis of gene expression profiles and expression of receptors (hormone receptors (HR) and HER2) as measured by immunohistochemistry. These subtypes have different prognoses and responses to treatments such as endocrine manipulation, anti-HER2 therapy, and chemotherapy. Triple-negative breast cancer (TNBC) is immunohistochemically defined as lacking estrogen and progesterone receptors and not overexpressing HER2. TNBC accounts for approximately 15% of breast cancer patients, and is more chemosensitive but has a worse prognosis than the HR-positive/HER2-negative phenotype. TNBC is a heterogeneous disease that does not offer specific targets in the same way as HR-positive and HER2-positive breast cancers, and is similar to basal-like breast cancer and BRCA1-related breast cancer. At present, the lack of highly effective therapeutic targets for TNBC leaves standard chemotherapy, for example the combination of anthracycline and taxane, as the only medical treatment, but this is insufficiently efficacious. Novel approaches for TNBC, for example DNA damaging agents, PARP-1 inhibitors, receptor tyrosin kinase inhibitors (TKIs), and antiangiogenesis agents, have been examined in clinical settings. Concerning therapeutic strategies for TNBC, it is most important to develop novel effective approaches for TNBC treatment and high-throughput predictive tools for standard chemotherapy and novel agents.     

Targeted chemotherapy for triple-negative breast cancers via LHRH receptor

Triple-negative breast cancer does not express estrogen and progesterone receptors and there is no overexpression/amplification of the HER2-neu gene. Therefore, this subtype of breast cancer lacks the benefits of specific therapies which target these receptors. About 60% of all human breast cancers express receptors for luteinizing hormone releasing hormone (LHRH, GnRH), which might be used as a target. The LHRH receptor can be used for targeted chemotherapy with cytotoxic luteinizing hormone releasing hormone agonists such as AEZS-108 (AN-152), in which doxorubicin is linked to [D-Lys6]LHRH. In the present study we have analyzed by in vitro and in vivo experiments whether the cytotoxic LHRH agonist AEZS-108 (AN-152) induces apoptosis in triple-negative human breast cancer cells that express LHRH receptors. LHRH receptor expression in tumor biopsy specimens of triple-negative breast cancers was tested using immunohistochemistry. Cell proliferation was analyzed using alamar blue proliferation assay. Induction of apoptosis was quantified by measurement of loss of mitochondrial membrane potential. In vivo experiments were performed using nude mice bearing xenografted human breast tumors.Thirty-one of 42 triple-negative breast cancers (73.8%) expressed LHRH receptors. We could show that treatment of triple-negative but LHRH-positive MDA-MB-231, HCC1806 and HCC1937 human breast cancer cells with AEZS-108 (AN-152) resulted in apoptotic cell death in vitro via activation of caspase-3. The antitumor effects were confirmed in nude mice. AEZS-108 (AN-152) inhibited the growth of xenotransplants of triple-negative human breast cancers in nude mice completely, without any apparent side effects. The cytotoxic LHRH agonist AEZS-108 (AN-152) seems to be a suitable drug for an efficacious therapy for triple-negative breast cancers with little toxicity.     

老年三阴性乳腺癌的临床病理特征及治疗

老年三阴性乳腺癌（TNBC）具有独特的临床病理特征,除浸润性导管癌,也多见于腺癌、小叶癌,该类肿瘤体积大,分级多为Ⅲ级。老年TNBC患者辅助化疗疗效显著,但因常并发其他疾病,选择治疗方案时除考虑肿瘤分期外,还需注意患者重要器官功能及耐受能力。老年TNBC患者预后较差,给予合理治疗后,情况可明显改善。     

Clinicopathological features of the triple-negative tumors in Chinese breast cancer patients

In order to analyze the clinicopathological features of Chinese triple negative tumors, we performed a retrospective study of 1993 female unilateral breast cancer patients undergoing surgery in Cancer Hospital of Fudan University, Shanghai, China. Survival curves were performed with Kaplan–Meier method and annual recurrence hazard was estimated by hazard function. We observed that the rate of larger tumors in triple negative patients was higher than that in HR+/ERBB2− women, but lower than that in ERBB2+ subgroup (P = 0.0001). In addition, 21.83% of triple negative patients had four or more axillary lymph nodes involved as compared to 27.40% of ERBB2+ women and 22.75% of HR+/ERBB2− subgroup (P = 0.0056). In the survival analysis, we found a statistical significance for recurrence-free survival (RFS) among the three subgroups (P = 0.0037), with the rate of 72.89% for ERBB2+ patients, 78.40% for HR+/ERBB2− ones and 75.76% for triple negative ones at the 11th year respectively. When it came to hazard peaks, discrepancies existed in different subgroups. Similar to HR+/ERBB2− patients, triple negative subgroup showed an early major recurrence surge peaking at approximately year 2.5 as opposed to ERBB2+ counterparts with a tapering sharp at the 1st year. Furthermore, the first peak of triple negative tumors was higher than that of HR+/ERBB2− patients, but lower than that of ERBB2+ ones. Therefore, our findings suggested biological characteristics and prognostic outlook of Chinese triple negative breast cancers might be more favorable and somewhat different from those in Western populations. W.-J. Yin, J.-S. Lu and G.-H. Di have contributed equally to this work.     

多病灶乳腺癌临床病理特征分析

目的探讨多病灶乳腺癌不同病灶临床病理特点的异同,以便更好地指导临床治疗。 方法回顾性分析2014年11月至2016年8月南京医科大学第一附属医院乳腺外科收治的41例多病灶乳腺癌患者的临床病理资料。分析多病灶乳腺癌不同病灶的常规病理、免疫组织化学检测结果及分子亚型的异同,并采用χ²检验比较多病灶乳腺癌与同期150例单病灶乳腺癌的病灶直径、组织学分级、淋巴结状态和脉管内癌栓状况。 结果41例多病灶乳腺癌患者中,有2处病灶者32例,3处病灶者8例,4处病灶者1例;病灶直径≤2 cm者18例,>2 cm者23例;不同病灶病理类型相同者33例(80%),不同者8例(20%);不同病灶组织学分级相同者38例(93%),不同者3例(7%);不同病灶免疫组织化学标志物ER、PR、HER-2、Ki67表达水平不同者分别为3例(7%)、6例(15%)、5例(12%)、3例(7%);分子亚型不同者5例(12%)。多病灶乳腺癌与单病灶乳腺癌患者相比,组织学分级3级、淋巴结转移及脉管内癌栓分布的差异均有统计学意义[51%(21/41)比32%(48/150), χ²＝5.154 ,P＝0.023;59%(24/41)比41%(61/150), χ²＝4.163 ,P＝0.041;29%(12/41)比8%(12/150), χ²＝13.257,P<0.001],但病灶直径的差异无统计学意义[56%(23/41)比56%(84/150),χ²＝0.001,P＝0.991)]。 结论多病灶乳腺癌不同病灶可存在不同的临床病理结果,因此,不同病灶均应进行常规病理与免疫组织化学检测,以便完整提供患者病理信息,选择最佳治疗方案。多病灶乳腺癌更易发生淋巴结转移及脉管内癌栓,提示可能预后较差。     

三阴性乳腺癌患者的临床特征与预后分析

Objective  

We investigated the clinical characteristics, and the prognostic factors of triple-negative breast cancer.     

Clinicopathological characteristics of p53 overexpression in endometrial cancers

Using immunohistochemical methods, we analyzed the association between nuclear p53 overexpression and various clinico-pathological parameters in patients with endometrial cancers. Formalin-fined and paraffin-embedded tissue sections from 139 cases of endometrial cancer (endometrioid type, 126; serous papillary type, 12; and clear-cell type, 1) were stained with anti-p53 monoclonal antibody (MAb) DO7. Overexpression of p53 was associated with high malignant potential, including extensive muscular invasion, advanced surgical stage, high histological grade, serous papillary type and a personal history of cancer. Lymph-node metastasis was also related to p53 overexpression with marginal significance. Survival curves determined by the Kaplan-Meier method and univariate analysis showed p53 overexpression to be associated with a poor outcome in endometrial cancer patients. However, multivariate analysis using the stepwise Cox proportional-hazard model showed that whereas lymph-node metastasis, a personal history of cancer and muscular invasion were related to poor survival rates, p53 overexpression was not. Consequently, p53 overexpression itself does not appear to be an independent prognostic factor in endometrial cancer, although a still larger sample of patient material would be required to assess this issue definitively. © 1994 Wiley-Liss, Inc.     

转移性三阴乳腺癌的临床特征和治疗结果

目的 分析转移性三阴乳腺癌的临床病理特征、生存情况和局部治疗在转移性三阴乳腺癌中的作用。方法 回顾分析1998—2013年间收治的 220例转移性三阴乳腺癌患者的临床特征和治疗结果。全组 206例初诊Ⅰ~Ⅲ期患者治疗后出现远处转移(186例接受改良根治术、14例保乳手术+放疗、5例单纯保乳术、1例未接受手术;化疗 196例,88例改良根治术后局部区域放疗),14例Ⅳ期初诊时即有远处转移(8例接受改良根治术、1例区段切除术、5例未接受手术)。用Kaplan-Meier法计算生存率,Logrank法检验和单因素预后分析转移后治疗对生存的影响。结果 最常见转移部位为肺和骨,实质性脏器转移182例(82.7%),单器官转移 63例(28.6%),多器官转移 153例(69.5%),4例不详。三阴乳腺癌初诊 3年内转移达高峰,5年后很少发生转移(6.4%)。中位随访时间22个月,全组转移后 5年OS为25.0%,中位生存时间21个月。单器官转移、多器官转移的 5年OS分别为38.2%、17.5%(P=0.005)。合并内脏转移、局限骨转移的 5年OS分别为20.3%、56.2%(P=0.049)。62例单器官转移病例中接受手术或放疗局部治疗组和无局部治疗组的转以后 5年OS分别为48%和29%(P=0.006)。结论 转移性三阴乳腺癌常见内脏实质器官转移,单器官转移预后好于多器官转移;对于单一器官转移,挽救性局部治疗能改善生存;局限于骨转移好于合并内脏转移预后。     

Clinicopathological significance and prognostic value of CD133 expression in triple-negative breast carcinoma

Currently, CD133 is one of the best markers to characterize cancer stem cells and Her-1 is reported as an important marker for the prognosis of triple-negative breast cancer. To investigate the relationship between the expression of CD133 and Her-1 and clinicopathology as well as prognosis in triple-negative breast cancer, 67 cases of triple-negative invasive ductal breast carcinoma taken from 422 patients with breast cancer were analyzed by immunohistochemistry and clinicopathology with follow-up. The CD133 and Her-1 were expressed as positive in 43.3% (29/67) and 53.7% (36/67) of patients, respectively. The expression of CD133 corresponded to tumor size (P = 0.022), clinical stage (P = 0.001) and lymphatic metastasis (P = 0.001), but not to age and histological grade. By Kaplan-Meier analysis the expression of CD133 was correlative with overall survival (OS) (log rank = 9.346, P = 0.002) and disease free survival (DFS) (log rank = 38.840, P = 0.0001) time of breast cancer patients. The expression of Her-1 was corresponding to tumor size (P = 0.031), clinical stage (P = 0.005) and lymphatic metastasis (P = 0.002), but not to age and histological grade. By Kaplan-Meier analysis the expression of Her-1 was correlative with overall survival (OS) (log rank = 7.998, P = 0.005) and DFS (log rank = 4.227, P = 0.040) time of patients with cancer. It is concluded that the expression of CD133 and Her-1 may be correlative with prognosis in triple-negative breast cancer.     

Comparison of molecular subtype distribution in triple-negative inflammatory and non-inflammatory breast cancers

Introduction

Because of its high rate of metastasis, inflammatory breast cancer (IBC) has a poor prognosis compared with non-inflammatory types of breast cancer (non-IBC). In a recent study, Lehmann and colleagues identified seven subtypes of triple-negative breast cancer (TNBC). We hypothesized that the distribution of TNBC subtypes differs between TN-IBC and TN-non-IBC. We determined the subtypes and compared clinical outcomes by subtype in TN-IBC and TN-non-IBC patients.

Methods

We determined TNBC subtypes in a TNBC cohort from the World IBC Consortium for which IBC status was known (39 cases of TN-IBC; 49 cases of TN-non-IBC). We then determined the associations between TNBC subtypes and IBC status and compared clinical outcomes between TNBC subtypes.

Results

We found the seven subtypes exist in both TN-IBC and TN-non-IBC. We found no association between TNBC subtype and IBC status (P = 0.47). TNBC subtype did not predict recurrence-free survival. IBC status was not a significant predictor of recurrence-free or overall survival in the TNBC cohort.

Conclusions

Our data show that, like TN-non-IBC, TN-IBC is a heterogeneous disease. Although clinical characteristics differ significantly between IBC and non-IBC, no unique IBC-specific TNBC subtypes were identified by mRNA gene-expression profiles of the tumor. Studies are needed to identify the subtle molecular or microenvironmental differences that contribute to the differing clinical behaviors between TN-IBC and TN-non-IBC.     

乳腺肌纤维母细胞瘤的临床诊治分析

目的：总结并探讨乳腺肌纤维母细胞瘤（myofibroblastoma,MFB）的临床特点及诊治方法。方法回顾性分析3例初治患者的临床资料及随访结果,分析总结本病的临床病理特点及诊治手段。结果3例患者均为绝经前女性,临床表现均为乳腺单发的小于2 cm的无痛性肿块。治疗均选择手术切除,术后均未行其他辅助治疗。术后石蜡病理结果证实均为MFB ,主要免疫组化指标SMA、Vimentin及Desmin均为阳性表达, S-100为阴性表达。患者术后均恢复良好并随访至2014年10月,随访期间均未见复发及远处转移。结论乳腺MFB是一种较少见的间叶组织来源的乳腺肿瘤,可见于绝经前女性,其临床表现及影像学表现无特异性,确诊往往依靠术后石蜡病理及免疫组化检查。本病预后良好,治疗以手术切除为主,较少复发。