Absence of correlation between risk factors for endometrial cancer and the presence of tamoxifen-associated endometrial polyps in postmenopausal patients with breast cancer

In order to investigate the presence of established risk factors for endometrial carcinoma in postmenopausal patients with breast cancer and with tamoxifen-associated endometrial polyps we compared a group of 25 patients with tamoxifen-associated endometrial polyps with 25 tamoxifen-treated patients without endometrial polyps. No significant differences were found between both groups of patients in age, parity, time after breast cancer and after menopause, duration and daily and total cumulative dose of tamoxifen intake, body mass index and serum levels of luteinising hormone (LH), follicle-stimulating hormone (FSH), oestradiol (E2), progesterone, sex hormone-binding globulin (SHBG), tamoxifen and CA125. So far there is no evidence that these polyps are premalignant lesions.     

MicroRNA与乳腺癌的相关研究进展

MicroRNA（miRNA）是真核生物中一类长度约为22个核苷酸的参与基因转录后水平调控的非编码小分子单链RNA,能通过与靶mRNA特异的碱基配对引起靶mRNA的降解或翻译抑制,从而对基因进行转录后的表达调控。目前普遍认为miRNA参与的基因调控是遗传程序中最基本的一步,调控着细胞分化、生长、凋亡、     

Origin and extension of intraductal papillomas of the breast: A three-dimensional reconstruction study

Summary Surgical specimens from fifteen patients with intraductal papilloma were reconstructed three-dimensionally from semi-serial sections to visualize the intraductal distribution of papillomas. Our results showed two basically different papillomas. In five patients, the papillomas were single and originated in the large ducts such as the segmental or subsegmental duct, but did not involve the terminal ductal-lobular units (TDLU); this type corresponded to the so-called solitary papilloma. In the remaining ten specimens, the papillomas were multifocal three-dimensionally; each had a root in the TDLU and spread into the large ducts, suggesting its purely peripheral origin. In view of this striking difference, and of possible canceration of ductal peripheries, a nomenclature of peripheral vs central papillomas is proposed instead of the conventional multiple vs solitary. Duct papillomatosis, invariably situated within the TDLU, was shown to be a continuation of peripheral papilloma and was regarded accordingly as a prepapillomatous condition.Presented in part at the 3rd Breast Cancer Working Conference EORTC, Amsterdam, April, 1983.     

铁死亡与乳腺癌治疗相关性的研究进展

铁死亡是近年来新发现的一种程序性细胞死亡形式,其特征是脂质活性氧的铁依赖性堆积,并在乳腺癌等疾病中起着重要的作用。乳腺癌是女性常见的恶性肿瘤之一,虽其病因及发病机制尚未阐明,但通过激活铁死亡途径能抑制乳腺癌细胞增殖,改善对化疗药物的耐药性,增强对放疗的敏感性及抑制癌细胞远处转移,可作为乳腺癌患者治疗的潜在新靶点。本文将对铁死亡发生机制及在乳腺癌治疗中的作用进行综述。     

肠道菌群与乳腺癌相关性研究进展

在最新发布的全球癌症报告中,乳腺癌发病率呈现逐年升高的趋势,跃居女性癌症发病率第一位,乳腺癌的防治成为重中之重.其发生受多种因素的影响,近年随着人类基因组计划的完成,肠道菌群相关基因被发现与多种疾病发生发展相关,并通过影响雌激素水平、免疫功能、乳房局部组织菌群等过程参与乳腺癌的多个病理过程,本文就近几年国内外文献探讨肠...     

72000IV型胶原酶的分泌和活化与肿瘤细胞转移潜能关系的研究

目的探讨肿瘤细胞转移潜能与７２０００ＩＶ型胶原酶的关系。方法采用明胶酶谱分析法,检测两组５种不同转移潜能的人癌细胞系,分泌７２０００ＩＶ型胶原酶的情况,以及人正常纤维母细胞在不同癌细胞的作用下,分泌的７２０００ＩＶ型胶原酶活性的改变。结果高转移潜能的癌细胞（ＰＧ、ＷＭ４５１和ＷＭ９８３ａ）分泌７２０００ＩＶ型胶原酶的量明显高于低转移潜能的癌细胞（ＰＡａ和ＷＭ３５）;在受ＰＧ和ＷＭ４５１细胞作用的纤维母细胞的条件培养液中,活化型７２０００ＩＶ型胶原酶的产量明显高于其他癌细胞作用的纤维母细胞。结论７２０００ＩＶ型胶原酶的表达和分泌与肿瘤细胞的转移潜能密切相关;高转移潜能的癌细胞（ＰＧ）和转移瘤细胞（ＷＭ４５１）可能通过分泌某些可溶性介质,刺激纤维母细胞,促进酶原型７２０００ＩＶ型胶原酶的活化,从而更有效地降解ＩＶ型胶原,达到转移的目的。     

乳腺导管内乳头状瘤的临床病理及预后分析

目的 乳腺导管内乳头状瘤是发生在乳头乳晕区的乳腺良性肿瘤,临床上较为常见.本研究探讨乳腺导管内乳头状瘤临床病理特征与复发的关系.方法 回顾性分析2010-01-01-2015-07 01中国医学科学院肿瘤医院547例乳腺导管内乳头状瘤患者的临床病理资料.结果 547例患者中,348例不伴有非典型增生(63.6％),199例(36.4％)伴有非典型增生.中位随访37个月,导管内乳头状瘤组和导管内乳头状瘤伴非典型增生组3年无复发生存率分别为98.2％和95.0％;3年无肿瘤生存率分别为99.1％和98.5％.2组无复发生存曲线比较差异有统计学意义,P=0.009.Cox分析结果显示,非典型增生是影响术后复发的主要因素,RR=0.183,95％CI=0.045～0.675,P-0.011;Logistic回归分析结果显示,伴有乳房肿物(OR=0.448,95％CI=0.29～0.68,P＜0.001)、外周型导管内乳头状瘤(OR=0.444,95％CI=0.45～0.72,P=0.001)术后病理更易出现非典型增生.结论 非典型增生情况是乳腺导管内乳头状瘤术后复发重要预测指标.     

Correlation between laminin and type IV collagen distribution in breast carcinomas, and estrogen receptors expression, lymph node and vascular involvement

The laminin (Lam) and type IV collagen (Coll IV) and estrogen receptor (ER) immunodetections were assessed in a large series of 400 human breast carcinomas. In all the cases the patient's age, the tumor size, the histological type and grade, the presence or the absence of axillary lymph node metastasis and of vascular invasion in tumor borders, and ER tumor content were recorded. Monoclonal anti-Lam, anti-Coll IV were applied with the avidin-biotin-peroxidase complex and monoclonal anti ER with peroxidase anti-peroxidase complex, on frozen sections. A computerized system of image analysis referred to as SAMBA (TITN) with specific software for tissue sections analysis permitted a multiparametric quantitative analysis of immunostained surfaces. With this system, in each tumor, the cellularity, the percentage of Lam, Coll IV and receptor positive surfaces versus the total cell surface and versus the epithelial (keratin positive) surface, the integrated optical density IOD histograms were obtained and correlated to morphometrical and standard histological data. From this study, it was shown that: (1) Lam and Coll IV immunostained epithelial basement membranes in carcinomas were correlated to the presence of estrogen and progesterone receptor antigenic sites within the tumors, with a significant decrease of the positive staining in ER-ICA negative tumors in comparison to ER-ICA/PR-ICA positive tumors. (2) The combined densitometric and morphometric evaluation demonstrated a decrease of Lam and Coll IV immunostaining in malignant tumors, correlated to (i) the presence of peritumorous vascular invasion and (ii) keratin positive cells in bone marrow (iii) axillary lymph node involvement. It is concluded that the variations in Lam and Coll IV antigens distribution may be relevant indicators of tumor metastatic potential in breast carcinomas and that computerized image analysis enables the standardization of the evaluation antigens distribution.     

Significant correlation between micrometastasis in the lymph nodes and reduced expression of E-cadherin in early gastric cancer

Background. E-cadherin has been recognized as an impor-tant factor associated with tumor metastasis. However, the relationship between micrometastasis in the lymph nodes and the expression of E-cadherin in the primary tumor in gastric cancer remains unclear. Methods. Two consecutive sections of 4522 lymph nodes from 162 patients with early gastric cancer were prepared for simultaneous hematoxylin and eosin (H&E) and cytokeratin (CK) staining. Sections of primary tumors from 135 of these patients were prepared for E-cadherin immunostaining. Results. The incidence of lymph node involvement was significantly increased, from 6.8% (11/162 patients) by H&E staining, to 27% (43/162 patients) by CK immunostaining ( P < 0.0001). Micrometastasis in the lymph node was found in 32 of 151 (21%) patients who had no lymph node metastasis evidenced by H&E staining. Micro-lymph node metastasis was frequently found in tumors with a diameter more than 1.0 cm, of those that were poorly differentiated, deeply invaded, showed lymphatic on vascular invasion, and in those that showed reduced expression of E-cadherin. Loss of expression of E-cadherin in the primary tumor was closely correlated with micro-lymph node metastasis. Patients with tumors with micro-lymph node metastasis detected by CK immunostaining had a significantly lower 5-year survival rate ( P < 0.01) than those without such metastases. Conclusion. Tumors more than 1.0 cm in diameter and those that exhibit poor differentiation, deep invasion (i.e., to the submucosa), lymphatic or vascular invasion, and reduced expression of E-cadherin are risk factors for lymph node metastasis in early gastric cancer. Thus, it is recommended that cancers confined to the mucosa (m-cancers) that are more than 1.0 cm in diameter should not be treated with limited surgery without lymphadenectomy. Received: March 27, 2001 / Accepted: May 10, 2001     

Association between breast cancer genetic susceptibility variants and terminal duct lobular unit involution of the breast

Terminal duct lobular units (TDLUs) are the predominant source of future breast cancers, and lack of TDLU involution (higher TDLU counts, higher acini count per TDLU and the product of the two) is a breast cancer risk factor. Numerous breast cancer susceptibility single nucleotide polymorphisms (SNPs) have been identified, but whether they are associated with TDLU involution is unknown. In a pooled analysis of 872 women from two studies, we investigated 62 established breast cancer SNPs and relationships with TDLU involution. Poisson regression models with robust variance were used to calculate adjusted per‐allele relative risks (with the non‐breast cancer risk allele as the referent) and 95% confidence intervals between TDLU measures and each SNP. All statistical tests were two‐sided; P < 0.05 was considered statistically significant. Overall, 36 SNPs (58.1%) were related to higher TDLU counts although this was not statistically significant (p = 0.25). Six of the 62 SNPs (9.7%) were nominally associated with at least one TDLU measure: rs616488 (PEX14), rs11242675 (FOXQ1) and rs6001930 (MKL1) were associated with higher TDLU count (p = 0.047, 0.045 and 0.031, respectively); rs1353747 (PDE4D) and rs6472903 (8q21.11) were associated with higher acini count per TDLU (p = 0.007 and 0.027, respectively); and rs1353747 (PDE4D) and rs204247 (RANBP9) were associated with the product of TDLU and acini counts (p = 0.024 and 0.017, respectively). Our findings suggest breast cancer SNPs may not strongly influence TDLU involution. Agnostic genome‐wide association studies of TDLU involution may provide new insights on its biologic underpinnings and breast cancer susceptibility.     

Can the clinical and mammographic findings at presentation predict the presence of an extensive intraductal component in early stage breast cancer?

The presence or absence of an extensive intraductal component (EIC) in early stage infiltrating ductal breast carcinoma has been considered to be an important factor in determining the extent of breast resection required prior to radiation therapy. It would therefore be useful if the presence or absence of an extensive intraductal component in a breast tumor could be predicted pre-operatively. To determine whether selected radiographic features might be correlated with whether or not a cancer is EIC+, we reviewed the pre-operative mammographic findings in 105 cases of Stage I and II infiltrating ductal carcinoma. Forty-one cases were EIC+ and 64 were EIC-. Both EIC+ and EIC- tumors were commonly detectable by mammography (93% and 83%, respectively, p = NS). EIC+ cancers, however, were significantly more likely to show microcalcifications with or without a mass compared to EIC- cases (83% vs 27%, p less than 0.0001). In particular, the presence of microcalcifications without a mammographic mass was more common for EIC+ cancers than EIC- cancers (34% vs 5% p = 0.0002). Conversely, a soft tissue mass without microcalcifications was seen mammographically in 56% of EIC- cases, compared to only 10% of EIC+ cases (p less than 0.0001). Predictive value calculations showed that the presence of microcalcifications in the absence of a mammographic mass conveys a 73% likelihood a cancer will be EIC+ (95% confidence interval = 39-94%). The positive predictive value of a mammographic mass or architectural distortion without microcalcifications for an EIC- cancer was 92% (95% confidence interval = 79-98%). We conclude that the mammographic findings may be useful pre-operatively in differentiating between patients with and without an EIC. Microcalcifications are much more commonly associated with EIC+ cancers than EIC- cancers, and the presence of an EIC- cancer without a mammographic mass is infrequent. Further characterization of the extent and pattern of microcalcifications might improve the predictive value of mammography in the pre-operative identification of patients with an EIC.     

雌激素受体表达与癌家族史阳性乳腺癌的关系

目的　为了探讨癌家族史阳性乳腺癌妇女ER水平是否高于非癌家族性乳腺癌者。方法　采用莹光组织化学法检测了本院 1985～ 1998年间 430例妇女可手术乳腺癌的新鲜组织ER水平 ,对其中癌家族史阳性乳腺癌ER与非癌家族性乳腺癌ER水平进行比较分析。结果　在 430例乳腺癌组织总的ER阳性率为 5 0 .2 % (2 16 / 430 ) ,其中绝经期前、后ER阳性率分别为 46 .3 % (6 8/ 14 7)和 5 0 .7% (10 7/ 2 11)。癌家族史阳性乳腺癌ER阳性率为 5 5 .1% (2 7/ 49) ;家族性乳腺癌ER阳性率为 72 .2 % (8/ 11) ;非癌家族性乳腺癌ER阳性率为 49.6 % (189/ 381)。结论　癌家族史阳性乳腺癌ER和家族性乳腺癌ER水平分别与非癌家族性乳腺癌ER相比 ,各呈明显增高倾向 ,但经统计学处理P >0 .0 5 ,认为无显著差异。本组乳腺癌病人中至少半数病例属于雌激素受体依赖性肿瘤 ,而且绝经期后水平略高于绝经期前者。     

Development of a biomimetic peptide derived from collagen IV with anti-angiogenic activity in breast cancer

Breast cancer is one of the most commonly diagnosed malignancies in women. Despite the remarkable success of mammography screening and use of adjuvant systemic therapy, it is estimated that approximately 200,000 new diagnoses will be made this year and 40,000 deaths will occur due to this disease (American Cancer Society). Angiogenesis, the growth of vessels from pre-existing microvasculature, is an essential component of tumor progression and has emerged as a therapeutic modality for anti-angiogenic therapies in cancer. Here we report in vitro and in vivo findings with a 20 amino acid peptide belonging to the collagen IV family, modified to facilitate possible translation to clinical applications. The two cysteines in its natural peptide progenitor were replaced by L-α-amino-n-butyric acid, a non-natural amino acid. The modified peptide was tested in vitro using endothelial cells and in vivo using mouse orthotopic breast cancer xenograft model with MDA-MB-231 human breast cancer cells. This modified peptide demonstrated no significant changes in activity from the parent peptide; however, because it lacks cysteines, it is more suitable for clinical translation. We also investigated its efficacy in combination with a commonly used chemotherapeutic agent paclitaxel; the inhibition of tumor growth by the peptide was similar to that of paclitaxel alone, but the combination did not exhibit any additional inhibition. We have performed further characterization of the mechanism of action (MOA) for this peptide to identify its target receptors, enhancing its translation potential as an anti-angiogenic, non-vascular endothelial growth factor (VEGF) targeting agent for therapy in breast cancer.     

黄芩素与乳腺癌侵袭转移关系的研究新进展

乳腺癌（breast cancer,BC）近年来有发病年轻及发病率上升的趋势,转移是晚期患者的最终阶段和导致乳腺癌患者死亡的主要原因。由于传统术后放化疗普遍存在严重的不良反应,因此从天然物质中寻找毒副反应小、安全有效的抗乳腺癌药物成为近些年的研究热点。黄芩素是一个广泛使用的中草药,具有广泛的抗肿瘤活性。本文主要简述黄芩素与乳腺癌侵袭转移关系的研究,综合阐述其对乳腺癌转移作用机制的影响。     

Ductal carcinoma in situ in core biopsies containing invasive breast cancer: correlation with extensive intraductal component and lumpectomy margins

BACKGROUND AND OBJECTIVES: The diagnosis of invasive breast cancer is most commonly made on image-guided core biopsy (CB). The presence of extensive intraductal component (EIC), as identified on subsequent lumpectomy, is associated with an increased risk of positive margins and need for further surgery. CBs demonstrating invasive breast cancer may also contain ductal carcinoma in situ (DCIS), although the significance of this finding is unclear. The objective of this study was to examine the implications of DCIS found in the original CB, specifically related to the risk of EIC and/or positive lumpectomy margins. METHODS: All patients at a single academic institution who underwent initial breast conserving surgery for invasive breast cancer diagnosed on image-guided CB between 05/00 and 04/02 were included in the study. A systematic, blinded review of all CB and lumpectomy specimens was performed using standardized criteria for DCIS, EIC, and margins. RESULTS: A total of 95 patients were included in the study, with a mean of 5 (median 5) CB/patient. Of these, 43 (45%) patients had DCIS identified in their CB; in 34 (79%) of these patients, the DCIS was mixed with the invasive cancer. No differences in tumor size or lumpectomy volume were identified between patients with or without DCIS on CB. However, patients with DCIS were noted to be significantly younger. Overall, EIC was identified in 13 (14%) patients; the risk of EIC was significantly higher in patients with DCIS identified in CB than in those with invasive carcinoma alone (30% vs. 0%, respectively; P < 0.0001). Expectedly, the incidence of positive margins on lumpectomy was higher in patients with EIC (38% vs. 16%; P = 0.05). A trend, although not statistically significant, towards positive margins was also noted in patients with DCIS on CB compared to those with invasive carcinoma alone (24% vs. 15%, P = 0.3). CONCLUSIONS: The identification of DCIS in conjunction with invasive cancer on CB appears important; the absence of DCIS in a CB sample excludes the possibility of eventually identifying EIC. Knowledge of DCIS in CBs with invasive carcinoma may be helpful for surgeons in planning gross resection margins at lumpectomy.     

乳腺癌与ALDH1相关性研究的现状

目的：总结近年来关于乙醛脱氢酶1（acetaldehyde dehydrogenase 1,ALDHl）特点的研究及其作为乳腺癌干细胞标志的相关性研究。方法：应用PubMed、Elsevier Sciencedirect和CNKI期刊全文数据库,以“乳腺肿瘤、ALDH1、干细胞、免疫组织化学、蛋白质组学”为关键词,检索2002—01—2012—11相关文献,共检索到256篇。排除标准：非乳腺癌和非ALDH1。纳入标准：1）ALDH1与乳腺癌的相关性研究;2）免疫组织化学方法及蛋白质组学研究乳腺癌干细胞。根据排除标准和纳入标准符合分析的文献18篇。结果：应用免疫组织化学、蛋白质组学和临床试验等方法的大量研究结果表明,ALDH1细胞能满足干细胞的定义标准,具有自我更新和多向分化的特性,并且已经在多种组织中证实了AL—DH1是一种有效的干细胞通用标志,兼之检测方法的多样化,使之成为多种组织类型干细胞鉴定和分离的有力工具,在干细胞研究领域具有特别重要的意义。作为乳腺癌干细胞标志之一,ALDH1与多种临床病理因素相关,在一定程度上可以反应疾病的恶性程度及预后,是导致乳腺癌发生、进展、耐药、复发和预后不良的根源,在临床上有非常重要的指导意义。结论：ALDH1可能具有自身独立的生物学特性,进一步深入研究其作为乳腺癌干细胞的特性,有助于发现新的关于ALDH1的靶点,为乳腺癌的个体化治疗提供理论依据。     

Host microenvironment in breast cancer development: epithelial-cell-stromal-cell interactions and steroid hormone action in normal and cancerous mammary gland

Mammary epithelial cells comprise the functional component of the normal gland and are the major target for carcinogenesis in mammary cancer. However, the stromal compartment of the normal gland and of tumors plays an important role in directing proliferative and functional changes in the epithelium. In vivo and in vitro studies of the murine mammary gland have provided insights into novel stroma-dependent mechanisms by which estrogen and progesterone action in the epithelium can be modulated by hepatocyte growth factor (HGF) and the extracellular matrix proteins, collagen type I, fibronectin and laminin. In vitro and in vivo studies of estrogen receptor positive, estrogen-responsive human breast cancer cells have also demonstrated that estrogen responsiveness of tumor cells can also be modulated by extracellular matrix proteins, collagen type I and laminin.     

Adhesion,growth and cytoskeletal characteristics of 8701-BC breast carcinoma cells cultured in the presence of type V collagen

Type V collagen is one of the minor components of the extracellular matrix (ECM) whose content is increased in cases of ductal infiltrating carcinomas of the breast. In order to clarify its biological role, we have investigated the effect of this molecule, both as substrate and as soluble factor, on the behaviour of a breast carcinoma cell line (8701-BC) grown in vitro. Cell-collagen adhesion was monitored for 24 h from plating in the absence or presence of serum. The influence of type V collagen on cell growth was followed during 9 days of culture, and the actin-vinculin arrangement was studied by simultaneous fluorescent immuno-staining. The results indicate that type V collagen is not a permissive substrate for neoplastic cell proliferation and dissemination in vitro.