人乳腺珠蛋白与乳腺癌

人乳腺珠蛋白（hMAM）是乳腺组织特异性表达的分泌性蛋白，目前被认为是一种具有临床应用前景的乳腺肿瘤标志物。现就MAM在乳腺癌肿瘤免疫治疗中的应用、作为乳腺癌肿瘤标志物的诊断现状和存在问题等方面探讨MAM在乳腺癌肿瘤疫苗的设计、诊断及转移检测的作用。     

乳腺癌组织与腋窝淋巴结中乳腺球蛋白的表达及其临床意义

目的:探讨乳腺球蛋白(MAM)在乳腺癌组织和腋窝淋巴结中的表达及其临床意义。方法:应用免疫组化法和RT-PCR法检测乳腺癌组织、非乳腺癌组织、乳腺癌腋窝淋巴结的MAM和MAM mRNA表达。结果:(1)MAM在乳腺癌组织表达的敏感度为88.8%,特异度为89.3%。MAM在乳腺癌组织和非乳腺癌组织中表达的差别有统计学意义(P<0.01)。(2)MAM的阳性表达与ER、PR状态(P=0.022和0.010)、组织分级(P=0.012)有关,与诊断时肿瘤大小、有无淋巴结转移、C-erbB-2状态、年龄无关。(3)MAMmRNA在乳腺癌腋窝淋巴结表达的灵敏度为90%,特异度为68.7%,阳性预测值为64.3%,阴性预测值为91.7%。结论:MAM是乳腺癌敏感且特异的标志物之一,有助于判断腋窝淋巴结转移存在。     

乳腺癌肿瘤标志物新的研究进展

目前乳腺癌已成为危害女性健康的第一大恶性肿瘤, 且发病率呈逐年递增趋势, 其早期诊断、治疗及预后成为当下研究的热点。乳腺癌肿瘤标志物对于其早期诊断、个体化治疗及预后均具有重要的临床实践指导意义。分子生物学的不断发展, 为乳腺癌肿瘤标志物的基础与临床研究奠定了良好的基础。近年来, 乳腺癌的诊断治疗手段逐渐增多, 肿瘤标志物的应用也不断受到青睐, 经典的肿瘤标志物已不足以更好的指导临床实践, 因此不断有新的肿瘤标志物出现。为了解乳腺肿瘤标志物在乳腺癌诊治中的重要作用及其相关最新研究, 本文结合国内外最新研究报道, 对乳腺肿瘤标志物新的研究进展做一简要综述。      

乳腺肿瘤标志物的研究进展

乳腺肿瘤标志物的检测与红外线扫描、数字X线、超声及磁共振成像扫描等影像学检查相结合提高了乳腺癌的诊断效率。预测预后的肿瘤标志物在个体化治疗和鉴别复发、转移的危险性方面有重要作用。到目前为止已有很多关于乳腺肿瘤标志物方面的研究。通过对总生存时间、无病生存时间、生活质量、毒性及费用一效益等方面的比较，有些乳腺肿瘤标志物的临床应用已被更新。     

肿瘤标志物和影像学检查诊断早期乳腺癌的研究进展

在中国女性恶性肿瘤发病率排名中,乳腺癌居首位。早期诊断乳腺癌尤为重要,其中肿瘤标志物和影像学检查是乳腺癌早期诊断的主要方法,随着近几年的科技发展,肿瘤标志物的研究方法新增了乳头溢液检测,乳腺超声方面新增了弹性成像技术,而乳房钼靶X线摄影术新增了对比度增强光谱技术。通过回顾近几年国内外学者对乳腺癌患者多肿瘤标志物和影像学检查以及乳腺成像报告和数据系统(BI-RADS)分级的研究,分析它们在乳腺癌早期诊断中的作用,为临床早期诊断提供新的方法和帮助。现就相关研究进展作一综述。     

乳腺癌相关血清肿瘤标志物的临床研究进展

癌胚抗原(CEA)、糖类抗原(CA)15-3、CA125等血清肿瘤标志物异常表达提示肿瘤的发生风险.CA15-3过表达被认为与乳腺癌的疾病进展有关,不同临床分期乳腺癌患者血清CA15-3的阳性检出率对诊断临床分期有显著优势,灵敏度和特异度均较高.但目前认为,某项血清肿瘤标志物单独检测对乳腺癌的阳性检出率较低,对早期筛查及诊断的意义不大,因此,多主张血清肿瘤标志物联合检测以对乳腺肿瘤进行早期筛查和早期诊断.本文对CEA、CA15-3、CA125等已在临床一定范围内得到应用的肿瘤标志物,以及新发现、潜在可能用于指导乳腺癌临床决策及治疗方案的肿瘤生物标志物与乳腺癌诊断、治疗及预后相关的临床研究进行综述.     

乳腺导管液检测与乳腺癌早期诊断

本文通过对连续９５１例乳腺疾病患者的乳腺导管液进行采集，特别是对于无乳头溢液患者进行乳腺导管插管，冲洗，采集冲洗液，用放免方法检测乳腺导管液中癌胚抗原（ＣＥＡ），铁蛋白（ＦＴ）和降钙素（ＣＴ），三种肿瘤标志物含量，进行乳腺癌早期诊断，检测结果表明，三种标志物中以ＣＥＡ敏感性和特异性较高，采用乳腺导管液三种标志物联合诊断早期乳腺癌特别是Ｔ０癌，微小癌符合率较高，该诊断方法明显优于Ｘ线等其它检查方法。     

乳腺球蛋白在术前乳腺癌和腋窝淋巴结细针穿刺吸取组织中的表达及临床意义

目的 探讨乳腺球蛋白（mammaglobin,MAM）在术前乳腺癌及腋窝淋巴结细针穿刺吸取组织中的表达及临床意义.方法 对91例原发性乳腺癌行术前细针穿刺,将吸取的组织制备涂片,采用免疫组织化学方法（EnVision法）检测MAM表达,观察MAM表达与临床病理指标的关系.同时另收集15例原发性肺癌腋窝淋巴结转移患者,分析乳腺癌腋窝淋巴结转移、乳腺癌增生性淋巴结炎和肺癌腋窝淋巴结转移三者间术前腋窝淋巴结MAM表达的区别.统计分析采用χ2检验.结果 在91例原发性乳腺癌患者中MAM的阳性表达率为74.72%（68/91）.MAM的阳性表达与雌激素受体（ER）、孕激素受体（PR）、组织学分级、细胞学分级有关（P〈0.05）,与患者的年龄、肿瘤大小、淋巴结是否转移及HER-2状态无关（P〉0.05）.腋窝淋巴结观察结果显示,MAM在乳腺癌腋窝淋巴结转移患者中呈阳性表达,在乳腺癌增生性腋窝淋巴结炎和肺癌腋窝淋巴结转移患者中均为阴性表达.结论 MAM可表达于原发性和转移性乳腺癌,细针穿刺细胞学检查结合MAM的测定对乳腺癌的诊断及鉴别具有一定辅助判断价值.MAM阳性表达与ER、PR状态、细胞学分级、组织学分级有关,有利于了解肿瘤的生物学指标及判断预后.     

人乳腺珠蛋白检测在乳腺癌诊断中的临床应用进展

乳腺癌是女性最常见的恶性肿瘤之一,早期发现、早期诊断乳腺癌是提高患者生活质量、延长患者生存期的关键。在当前所有的医学手段中,对于无症状的肿瘤患者,肿瘤标志物常常是最早期发现肿瘤的方法之一。人乳腺珠蛋白（human mamrnaglobin,hMAM）是特异地表达于乳腺上皮细胞、原发性乳腺癌组织的分泌性球蛋白,目前被认为是1种具有临床应用前景的乳腺癌肿瘤标志物。     

乳腺癌相关分子hMAM的临床应用

人乳腺珠蛋白(hMAM)为近几年发现的一种乳腺组织特异性蛋白，其基因仅在乳腺癌中表达，可能是首次发现的具有乳腺器官特异性的肿瘤标志物。该标志物的确认无疑会对乳腺癌的诊治等方面带来突破性进展。目前国内外学者对hMAM的表达及其与乳腺癌的关系做了大量研究，提出了许多新的思路及线索。现对其在乳腺癌中的早期诊断、治疗、监测病程转移及复发中的研究进展进行综述。     

Primary Breast Lymphoma After Mastectomy With Reconstruction

Primary breast lymphoma accounts for only 0.05%–1.1% of all breast malignancies, and less than 1% of all cases of non-Hodgkin lymphoma. Although primary breast lymphoma may present clinical similarities to breast carcinoma, the majority of cases lack the typical features of breast malignancy or lymphoma. We describe a case of primary breast lymphoma in a reconstructed breast, 8 years after a mastectomy for breast cancer. To the best of our knowledge, this is the first reported case in the worldwide literature of primary breast lymphoma in a reconstructed breast. We will discuss the diagnostic and treatment strategies involved in the management of primary breast lymphoma, and the effect of breast reconstruction on the detection of recurrent breast cancer.     

Dietary and other risk factors in women having fibrocystic breast conditions with and without concurrent breast cancer: a nested case-control study in Shanghai, China

Risk of breast cancer is increased in women with proliferative benign breast conditions. Most of these conditions, however, do not progress to breast cancer. The purpose of our study was to identify factors possibly associated with this progression. Women with proliferative fibrocystic breast conditions alone (214), and women with proliferative fibrocystic breast conditions and concurrent breast cancer (130), were compared to each other, and each of these groups of women were also compared to 1,070 controls; and 176 women with non-proliferative benign breast conditions alone, and 155 also with breast cancer, were similarly compared. All study subjects were selected from a cohort of women enrolled in a trial of breast self-examination in Shanghai. Women were interviewed to ascertain information on suspected risk factors for breast cancer and dietary habits. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Increased risks of both proliferative fibrocystic breast conditions alone, and with breast cancer, were associated with low parity, a prior benign breast lump and breast cancer in a first-degree relative. Decreasing trends in the risk of both conditions with increasing intake of fruits and vegetables were observed. No factors were significantly associated with risk of breast cancer relative to risk of proliferative changes. Similar, but in some instances weaker, associations were observed for non-proliferative fibrocystic conditions with and without breast cancer. The possible risk or protective factors that were observed in our study most likely alter the risk of breast cancer at an early stage in the carcinogenic process, and probably do not alter risk of progression from proliferative fibrocystic breast conditions to breast cancer.     

乳腺密度与乳腺癌相关性研究（附825例）

目的:研究乳腺密度与乳腺癌之间的关系,探讨影响乳腺癌患者乳腺密度的相关因素。方法:回顾性分析825例乳腺钼靶受检者的临床资料,其中237例经病理诊断确诊为乳腺癌,588例为乳腺良性对照组。按照BI-RADS标准,将乳腺密度分为＜25%、25%~50%、51%~75%及>75%共4个等级,分析不同的乳腺密度与乳腺癌危险因素的关系。结果:乳腺癌组与乳腺良性对照组之间的乳腺密度有显著统计学意义（P<0.001）,对于乳腺癌患者,绝经状态（P<0.001）和哺乳史（P<0.001）分别与乳腺密度有统计学意义;初潮时间对乳腺癌患者乳腺密度影响无显著统计学意义。结论:高密度的乳房患乳腺癌的风险偏高,乳腺癌患者的绝经状态、哺乳史、初潮时间对乳腺密度有一定影响。     

Breast cancer arising in surgical scars

Twelve women who developed breast cancer at the site of old surgical scars in the breast are presented. Six had had former breast biopsies, 3 drainage of breast abscesses, and 3 developed breast cancer in old thoracotomy scars transversing the breast. The combination of trauma as an oncogen and scar tissue as a functional and immunological locus minoris resistentia seems to play a major role in the development of breast cancer in this group of patients. The association of breast cancer, scar, and trauma would not be coincidental. Increased attention drawn to this entity may lead to a rise in the number of cases diagnosed among patients with breast scars after biopsies, abscesses, trauma, or foreign body implantation.     

Do fatty breasts increase or decrease breast cancer risk?

Few studies have investigated the association of non-dense area or fatty breasts in conjunction with breast density and breast cancer risk. Two articles in a recent issue of Breast Cancer Research investigate the role of absolute non-dense breast area measured on mammograms and find conflicting results: one article finds that non-dense breast area has a modest positive association with breast cancer risk, whereas the other finds that non-dense breast area has a strong protective effect to reduce breast cancer risk. Understanding the interplay of body mass index, menopause status, and measurement of non-dense breast area would help to clarify the contribution of non-dense breast area to breast cancer risk.     

Women's interest in genetic testing for breast cancer risk: the influence of sociodemographics and knowledge.

The objective of this study was to assess women's interest in genetic testing for breast cancer risk. Randomly selected samples of 761 women without breast cancer from the general population of British Columbia, Canada, and 260 women with breast cancer from the provincial cancer registry participated in a telephone survey that assessed interest in genetic testing for breast cancer risk, knowledge of hereditary breast cancer and genetic testing, and sociodemographics. Women with breast cancer did not possess superior knowledge of breast cancer genetics compared with women from the general population. Of the women with breast cancer, 30.8% reported interest in testing or had been tested, compared with 28.5% of women without breast cancer. Controlling for differences in age, education, personal history of breast cancer, and knowledge of genetics, women with at least one relative with breast cancer were 2.3 times more likely to express interest in genetic testing for breast cancer risk than those with no family history. There were significant interactions between breast cancer status and education and between age and knowledge of breast cancer genetics. Women without breast cancer and with a positive family history, who were between 20 and 40 years of age, were most likely to be interested in testing. The women with breast cancer who were interested in testing tended to be approximately 50 years of age, had a positive family history, and had more years of education. Women with a family history of breast cancer, well-educated women with breast cancer, and younger women, particularly those with knowledge of genetic testing, are important target audiences for community-based education on genetic testing for breast cancer risk.     

Identification of distinct protein expression patterns in bilateral matched pair breast ductal fluid specimens from women with unilateral invasive breast carcinoma. High-throughput biomarker discovery

BACKGROUND: Analysis of the biochemical and cellular contents of breast ductal fluid has recently gained attention as a potential noninvasive method for studying the local microenvironment associated with the development and progression of breast carcinoma. METHODS: Patients with unilateral primary invasive breast carcinoma were eligible for the current prospective pilot study. Nipple aspiration fluid (NAF) was obtained from the breast with cancer and the normal contralateral breast and subjected to two-dimensional electrophoresis. Computer-assisted image analysis was used to analyze NAF protein expression profiles. RESULTS: The number of separate protein spots detected in NAF samples ranged from 1280 to 1649. Substantial qualitative differences were identified between NAF protein expression patterns in the breast with cancer compared with the breast without cancer. Protein spots detected in the breast with cancer and not in the breast without cancer from the same patient varied from 30 to 202 different proteins. In addition, the number of protein spots detected in the breast without cancer and not in the breast with cancer of the same patient varied from 14 to 73 different proteins. Conversely, in an individual without breast carcinoma, only three protein spots were detected in the left breast but not the right breast, and only two were detected in the right breast but not the left breast. CONCLUSIONS: The breast is a unique organ in that its microenvironment can be readily accessed and evaluated by aspiration of fluid from the nipple. Breast ductal fluid contains a large number of proteins. As breasts are paired organs, comparisons of ductal fluid from a breast with cancer and the same patient's normal contralateral breast may reveal significant differences in protein expression associated with breast carcinoma. Recent advances in image analysis, automated mass spectrometry, and bioinformatics have provided the tools necessary to use ductal fluids from breast carcinoma patients for high-throughput biomarker discovery.     

Pre-cancerous breast lesions: implications for breast cancer prevention trials.

The relationship between benign breast disease and breast cancer has become the focus of increased clinical attention as breast cancer prevention becomes a clinical reality. In this setting an understanding of the magnitude of the increase in risk conferred by the various types of benign breast disease assumes increasing importance. When benign breast disease is considered as an aggregate, estimates of the relative risk of breast cancer development range from 0.8 to 4.5. This article describes the risk associated with proliferative and non-proliferative benign breast disease, as well as the rationale for considering lobular carcinoma in situ and ductal carcinoma in situ (in some cases) as risk factors for breast carcinoma rather than actual malignant lesions. Mathematical models can provide a more precise estimate of breast cancer risk, but these efforts may be confounded by the lack of uniformity in the pathologic definition of borderline benign breast lesions. The breast cancer prevention trials offer a unique opportunity to improve our database on the natural history of high risk benign breast lesions, while attempting to reduce the 44,000 deaths occurring annually from breast cancer.     

Mammographic breast density as an intermediate phenotype for breast cancer

The amount of radiologically dense breast-tissue appearing on a mammogram varies between women because of differences in the composition of breast tissue, and is referred to here as mammographic density. This review presents evidence that mammographic density is a strong risk factor for breast cancer, and that risk of breast cancer is four to five times greater in women with density in more than 75% of the breast than in women with little or no density in the breast. Density in more than 50% of the breast could account for about a third of breast cancers. The epidemiology of mammographic density is consistent with its being a marker of susceptibility to breast cancer. Twin studies have shown that the proportion of the breast occupied by density, at a given age, is highly heritable, and inherited factors explain 63% of the variance. Mammographic breast density has the characteristics of a quantitative trait and might be determined by genes that are easier to identify than those for breast cancer itself. The genes that determine breast density might also be associated with risk of breast cancer, and their identification is also likely to provide insights into the biology of the breast and identify potential targets for preventive strategies.     

Knowledge of Breast Density and Awareness of Related Breast Cancer Risk

Little is known about women’s knowledge of breast density or between-race differences in this knowledge. In the current study, we examined knowledge of breast density and awareness of its role as a breast cancer risk factor among women who had previously taken part in a breast imaging study. Seventy-seven women (54.5 % Black) returned a survey assessing perceptions and accuracy of breast density knowledge, knowledge of one’s own breast density, and breast cancer risk awareness. White women had greater perceived knowledge of breast density compared to Black women; however, differences in the accuracy of definitions of breast density were due to education. Black women were less likely to know how dense their own breasts were. Black and White women both lacked awareness that having dense breast increased breast cancer risk. The results highlight the need to disseminate information regarding breast density to women, while ensuring that the information is equally accessible to both Black and White women.