超声剪切波弹性模量与乳腺病灶良恶性及乳腺癌分子亚型的相关性

目的 探讨超声剪切波弹性模量与乳腺病灶良恶性及乳腺癌分子亚型的相关性。方法 选取104例行乳腺常规超声及超声剪切波弹性成像检查的患者,经手术切除或活检穿刺后病理检查确诊为116个病灶。比较良恶性病灶超声剪切波弹性模量值最大值,分析超声剪切波弹性模量值最大值与乳腺癌病理参数,经spearman分析两者相关性。结果 病理检查结果显示116个病灶中,乳腺良性病灶74个,恶性病灶42个。恶性病灶弹性模量最大值显著高于良性病灶(P<0.05)。超声剪切弹性模量最大值与乳腺癌组织分级无关(P>0.05),与肿瘤大小、分子亚型有关(P<0.05)。经spearman相关性分析,乳腺癌肿瘤大小、分子亚型与弹性模量最大值成正相关(P<0.05)。结论 超声剪切波弹性成像能有效判断乳腺病灶良恶性,且其弹性模量最大值与乳腺癌分子亚型成正相关,可为乳腺癌预后判断及治疗提供一定参考依据。     

男性乳腺癌病理分子亚型与预后的相关性分析

目的:研究男性乳腺癌分子亚型与预后的关系.方法:回顾性分析男性乳腺癌患者的临床随访和病理资料,应用x2检验分析分子亚型与临床病理特征的关系,用Kaplan-Meier生存曲线(Log-Rank法)和Cox风险比例回归模型比较不同分子亚型组间预后的差异.结果:68例男性乳腺癌患者具有完整的病理及随访资料并纳入分析.中位随...     

动态增强磁共振与乳腺癌分子亚型血管生成的相关性研究

目的 动态增强磁共振成像(dynamic contrast enhanced magnetic resonance imaging,DCE MRI)为乳腺癌敏感度最高的检查方法之一,能够显示病灶血供情况而间接评价病灶微血管生成情况.探讨DCE-MRI半定量参数达峰时间(the time to peak enhancement,TTP)、早期增强率(early-phase enhancement rate,El)、最大线性斜率(SLOPE)与乳腺癌不同分子亚型血管生成的相关性,及比较乳腺癌4种不同分子亚型血管生成的特点.方法 收集山东省肿瘤医院2012-12-01-2015 03 31经手术确诊的103例乳腺癌患者,术前1周内行DCE-MRI扫描,记录上述参数,对切除病变行常规病理和免疫组化检查,根据免疫组化结果分为4种不同分子亚型,观察微血管密度(microvessel density,MVD)计数和血管内皮生长因子(vascular endothelialgrowth factor,VEGF)的表达,并将不同分子亚型DCE-MRI各项参数与免疫组化结果进行相关性分析.结果 4种不同分子亚型的各动态增强参数差异均无统计学意义;三阴型乳腺癌MVD值(79.47±49.79)明显高于Luminal B型(50.89±18.21),P=0.02;除Luminal A型与Luminal B型外,其他各亚型之间VEGF表达差异均有统计学意义,P＜0.001;三阴型乳腺癌的MVD与DCE MRI的关系最密切,r-0.55,P=0.015;MVD与EER、SLOPE呈正相关,r=0.859,P＜0.001;与TTP呈负相关,r=-0.60,P=0.007.Luminal A型乳腺癌MVD与EER(r=0.71,P＜0.001)和SLOPE呈正相关(r=0.51,P=0.001).结论 三阴型乳腺癌较两种Luminal表现为更丰富的血管生成,三阴型及Luminal A型MVD与DCKMRI半定量参数EER、SLOPE存在一定的相关性.     

不同分子亚型乳腺癌与腋窝淋巴结转移的相关性分析

目的 探讨乳腺癌不同分子亚型与腋窝淋巴结转移的关系.方法 对127例乳腺癌患者进行分子分型,并对其腋窝淋巴结转移状态进行分析.结果 127例中Luminal A型50例,8例淋巴结转移,转移率为16.0%;Luminal B1型28例,16例淋巴结转移,转移率为57.1%;Luminal B2型15例,3例淋巴结转移,转移率为20.0%;HER-2过表达型25例,7例淋巴结转移,转移率为28.0%;Basal-like型9例,6例淋巴结转移,转移率为66.7%.结果显示,不同分子分型乳腺癌的腋窝淋巴结转移阳性率差异显著.结论 根据乳腺癌的分子分型可以间接了解患者腋窝淋巴结的转移情况,或对腋窝淋巴结清扫术指征的制定提供帮助.     

肿瘤浸润淋巴细胞对不同分子亚型乳腺癌预后效应的研究进展

肿瘤浸润淋巴细胞（tumor infiltrating lymphocytes,TILs）是肿瘤微环境的重要组分,对结肠癌、肺癌等多种肿瘤预后有明确的指示效应。在乳腺癌中,相关研究的结论并不一致。考虑到乳腺癌是一组由多种不同分子亚型组成的异质性疾病,TILs对不同分子亚型乳腺癌的预后指示作用也不同。本综述阐述常用TILs指标对不同分子亚型乳腺癌预后指示效应的相关研究进展。     

218例不同分子亚型浸润性乳腺癌患者的临床特征

目的：探讨浸润性乳腺癌分子亚型在中国人群中的分布,以用于判断临床预后和指导治疗。方法：回顾分析218例浸润性乳腺癌患者,根据雌激素受体（ER）、孕激素受体（PR）、人类表皮生长因子受体2（HER2）的水平划分为4个分子亚型。对比分析4型患者的分布比例、发病年龄、病理组织学分类、肿瘤最大径以及淋巴结转移等相关因素。结果：在4型中,luminal A型例数最多,共131例（60.1%）;basal-like型共有63例（28.9%）;luminal B型和HER2过表达型所占比例较少,均为12例（5.5%）。发病年龄以40岁～59岁年龄段发生乳腺癌例数最多,达到77.06%。HER2过表达型在50岁～59岁年龄段发病例数显著增高,与其余3组相比有显著性差异（P〈0.05）。病理分类显示,浸润性导管癌最多,各型之间无显著性差异（P〉0.05）;从淋巴结阳性病例中,HER2过表达型和luminal B型多枚淋巴结转移比例更高（P〈0.05）。肿瘤最大径分析显示,HER2过表达型和basal-like型病例肿瘤最大径2cm～5cm的比例较高,而luminal A型和luminal B型的肿瘤最大径多小于2cm（P〈0.05）。结论：在4型中,luminal A型所占比例最高;HER2过表达型在50岁～59岁年龄段发病较多见;浸润性导管癌是最常见的病理组织类型;HER2过表达型和luminal B型多枚淋巴结转移情况更多发生;HER2过表达型和basal-like型肿瘤较luminal A型更大。     

乳腺癌的分子亚型及治疗策略研究进展

随着分子生物学基因技术在乳腺癌研究中的广泛应用,目前可将乳腺癌分为Luminal、HER-2^＋、Triple negative 3种分子亚型。这3种亚型乳腺癌均有各自不同的生物学特性,对于乳腺癌治疗方法的选择及预后的预测有非常重要的意义。本文对上述3种乳腺癌亚型的生物学特性、治疗选择及预后分别进行综述。     

剪切波弹性成像定量技术诊断乳腺良恶性肿瘤的临床研究

目的用剪切波弹性成像技术（SWE）定量测定乳腺良恶性肿瘤弹性模量值,评价对乳腺癌的诊断价值和临床意义。方法以中国医科大学附属第四医院415例女性乳腺肿瘤患者为研究对象,测定乳腺病变组织最大弹性模量值（Emax）和平均弹性模量值（Emean）,分析与乳腺癌不同临床分期、分级及肿瘤大小的相关性,绘制ROC 曲线,并计算其曲线下面积（AUC）。结果乳腺癌晚期（Ⅲ期+Ⅳ期）Emax和Emean高于早期（Ⅰ期、Ⅱ期）,且Ⅱ期Emax和Emean高于Ⅰ期,组织学分级Ⅲ级（低分化）Emax和Emean高于Ⅱ级（中分化）、Ⅰ级（高分化）,且Ⅱ级（中分化）高于Ⅰ级（高分化）;肿瘤大小与Emax和Emean呈正相关。ROC曲线显示,良恶性肿瘤诊断Emax及Emean临界值分别为：605 kPa、315 kPa,其诊断灵敏度、特异度、准确性分别为：908％、962％、935％和899％、919％、908％。结论剪切波弹性成像定量技术对诊断乳腺良恶性肿瘤具有重要的价值和临床意义。     

青年女性乳腺癌的影像学特征与免疫组织化学分子亚型相关性分析

背景与目的：乳腺癌在30岁以下的青年女性中很罕见,但近几年乳腺癌趋向年轻化并且发病率逐年增高,而早期乳腺癌免疫组织化学分子亚型的识别可以完善治疗方案。该研究旨在探讨青年女性（≤30岁）乳腺癌的超声、数字乳腺Ｘ线摄影（digital mammography,DM）及数字乳腺断层合成摄影（digital breast tomosynthesis,DBT）特征与免疫组织化学分子亚型的相关性。方法：回顾并分析2013年12月—2019年7月于青岛大学附属医院进行过乳腺超声、DM和DBT检查,且经手术后病理学检查证实为乳腺癌,年龄≤30岁的139例青年女性患者。影像学特征参照第5版乳腺影像报告及数据系统（Breast Imaging Reporting and Data System,BI-RADS）进行评估及分类。对肿块样病变,3种检查方法均评估了病变的形状、边缘,DM和DBT对肿块密度另加以评估,超声对病变内部回声、后方回声、血流信号另加以评估;对异常钙化评估其形态及分布;依据BI-RADS评估了乳腺纤维腺体构成;分子亚型根据2015年修订的St. Gallen国际专家共识建议确定。结果：病变多表现为可触及肿块（89.9%）、临床T ₂ 期（50.4%）、组织学Ⅱ级（58.3%）、腋窝淋巴结转移（59.7%）、luminal B型乳腺癌（44.6%）,BI-RADS多为4类或5类。在所有成像中,肿块病变均多表现为不规则形（P<0.001）,luminal A型乳腺癌及三阴性乳腺癌（triple-negative breast cancer,TNBC）多为肿块样病变,luminal B型乳腺癌中肿块伴钙化病变多见,HER2过表达型多见单纯钙化样病变（P<0.001）。在DM和DBT上,诊断为阴性情况更常见于luminal A型乳腺癌（P<0.001）。对于肿块样病变,DM中最常见表现为边缘模糊（71.9%）,而DBT多见毛刺影（51.8%）,毛刺边缘多与luminal A和luminal B型乳腺癌相关（P<0.01）。良性影像学特征多与TNBC相关,表现为卵圆形或圆形（P<0.001）,边缘清楚（P<0.01）。HER2过表达型和TNBC型两组中肿块病变的范围均大于luminal A和luminal B型乳腺癌（P=0.003）。结论：30岁以下青年女性乳腺癌的部分影像学特征可用于预测某些肿瘤免疫组织化学分子亚型。DBT的乳腺癌检出率高于DM,对乳腺致密的青年女性具有广泛的应用价值。     

基于DWI和DCE-MRI的影像特征对四种不同分子亚型乳腺癌的诊断价值探讨

目的:基于弥散加权成像（diffusion weighted imaging,DWI）和动态增强MRI（contrast-enhancement magnetic resonance imaging,DCE-MRI）的影像特征对Luminal A型、Luminal B型、人类表皮生长因子受体（human epidermal growth factor receptor-2,HER-2）过表达型和三阴型（triple negative,TN）四种不同分子亚型乳腺癌的诊断价值探讨。方法:选取2016年9月至2018年9月我院收治确诊为乳腺癌的患者98例,所有患者行DWI及DCE-MRI扫描,后行乳腺癌手术行病理分子分型鉴定。采用Mann-Whitney U检验和单因素logistic回归法进行各变量单因素分析,采用多因素logistic回归法对单因素分析中有统计学意义的变量进一步分析并建模,使用受试者工作曲线（receiver operating characteristic curve,ROC）评估模型的诊断效能,采用Hosmer-Lemeshow 检验对模型的拟合优度进行检验。结果:患者分子病理分型Luminal A型32例,Luminal B型45例,HER-2过表达型10例,TN型11例。ADC、IER值在鉴别乳腺癌分子分型时AUC＜0.07,诊断效能较低;影像学特征鉴别分子分型时,显示DCE_bior3.1_3_correlation 鉴别 Luminal A型乳腺癌 AUC=0.732;ADC_rbio1.1_1_sum_variance鉴别Luminal B型乳腺癌AUC=0.722;鉴别HER-2过表达型乳腺癌ADC_L_G_2.5_min AUC=0.747;鉴别TN时5个影像学特征AUC 均 >0.70。鉴别Luminal A和非Luminal A型的模型为0.005×ADC_rbio1.1_1_sum_variance+0.032×DCE_bior3.1_3_correlation－0.273;鉴别Luminal B和非 Luminal B型的模型为－0.008×ADC_rbio1.1_1_sum_variance－0.003×DCE_rbio3.1_3_variance+3.204;鉴别 TN和非TN 的模型为-0.163×DCE_L_G_2.5_autocorrelation+8.904,各个鉴别诊断的AUC分别为0.787 6、0.744和0.773。经Hosmer-Lemeshow检验各模型P值均>0.05,各个模型预测值与观测值之间差异无统计学意义,模型拟合效果较好。结论:MRI影像学指标ADC、IER值鉴别乳腺癌分子亚型价值有限,DWI和DCE-MRI相关影像学特征鉴别乳腺癌分子亚型有一定价值。     

Relationship Between Breast Density,Breast Cancer Subtypes,and Prognosis

BackgroundIn the United States, Europe, and Asia, a consensus has been reached that there is a higher risk of breast cancer in high density breasts. However, there are some contrary reports that suggest the absence of an association between breast composition and breast cancer subtype; thus, there is conflicting evidence. The purpose of this study was to investigate trends in the incidence of breast cancer subtypes according to breast composition and analyze the survival rates in Japanese women.Patients and MethodsBetween 2007 and 2008, 1258 Japanese patients with invasive breast cancer who underwent mammography and obtained a pathological diagnosis in our institution were included in the study. We compared cancer subtypes with breast composition types (dense and non-dense breast), and classified them based on initial mammography findings. Information on 5- and 10-year survival rates was collected by chart review for patients with dense and nondense breasts. Statistical analysis was performed using the Pearson's chi-square test for breast composition and cancer subtype. The effect of breast composition on mortality was examined using a multivariate Cox proportional hazards model, and adjusted hazard ratios were calculated.ResultsNo significant difference was found between breast cancer subtype and breast composition (P = .08). Five-year (log-rank test, P = .09) and 10-year (log-rank test, P = .31) survival rates were not significantly different between breast composition types.ConclusionThere was no significant association between breast composition and cancer subtypes. There was also no significant difference in the prognosis between patients with and without dense breasts.     

Survival Time and Molecular Subtypes of Breast Cancer after Radiotherapy in Thailand

Background: Breast cancer is an important cause of death among women. One way of classifying differentforms of breast cancer is by molecular features, usually in terms of the four subtypes: luminal A, luminalB, HER2-enriched, and triple negative. Objectives: This study aimed to investigate the association betweenmolecular subtypes and survival among breast cancer patients treated with radiotherapy. Materials and Methods:A retrospective cohort study was conducted. The subjects were 272 breast cancer patients who had receivedtreatment in the radiotherapy unit at Srinagarind Hospital, Thailand, between 1 January, 1999, and 31 May,2009. The end of the study was 1 June, 2014. Overall survival was defined as the time elapsing between initialregistration at the radiotherapy unit and death or the end of the study. Survival curves were estimated by theKaplan-Meier method, and a multivariate analysis was performed using Cox’s proportional hazard regressionmodel. Results: The patient mean age was 47.5±10.4 at the time of diagnosis. Of the 272 patients, 146 (53.7%)were classified as luminal A, 12 (4.4%) as luminal B, 30 (11.0%) as HER2-enriched, and 84 (30.9%) as triplenegative. The overall survival rates at 1, 3 and 5 years were 87.1%, 68.4% and 59.2%, respectively. According tomolecular subtypes, HER2-enriched patients had the lowest 5-year survival rate (30.0 %, 95%CI: 15.02-46.55).The median follow-up time was 8.37 years. In the Cox model analysis a higher risk of death was found for patientswith HER2-enriched (HRadj=3.34, 95%CI:1.96-5.67), triple negative (HRadj=2.17, 95%CI: 1.44-3.27), and stageIIlB (HRadj=2.20, 95%CI: 1.16-4.17) cancers. Conclusions: The worst survival rates were among patients classifiedas HER2-enriched, triple negative and at stage IIIB. Early detection and an advanced treatment modality areneeded to help these patients.     

乳腺浸润性导管癌分子分型与临床特征的关系

目的探讨乳腺浸润性导管癌不同分子亚型的分布,并分析各分子亚型与临床特征的关系。方法收集2006年1月-2011年6月明确诊断为乳腺浸润性导管癌病例100例,根据雌激素受体（ER）、孕激素受体（PR）、表皮生长因子受体-2（HER-2）的表达情况划分为四型,进一步分析不同分子亚型与浸润性导管癌临床特征的关系。结果100例中Luminal A型所占比例最大为65%,7%为Luminal B型, Triple Negative型占17%,Her-2(+)型占11%。各分子亚型乳腺浸润性导管癌患者发病年龄主要集中在40~59岁之间,占73%,Luminal A型发病年龄主要集中在40~49岁,而其他三型主要分布于50~59岁,四型在不同年龄组的分布上差异有统计学意义（P＜0.05）;Luminal A型淋巴转移发生率仅为30.1%,而Luminal B型与Her-2(+)型淋巴转移发生率较高,分别为71.4%及63.6%,各分子亚型的腋窝淋巴结转移率有显著差异（P＜0.05）;病理组织学分级Ⅰ级中Luminal A型所占比例最高,而Triple Negative型主要以Ⅲ级为主,差异具有统计学意义（P＜0.05）。结论乳腺浸润性导管癌各分子亚型分布差异具有统计学意义,各分子亚型与其临床特征关系密切。     

Tumor-Associated Neutrophils in Breast Cancer Subtypes

Background: Tumor associated neutrophils (TAN) are related to aggressiveness and a poor prognosis with human cancers. However, the relevance of TAN in breast cancer has not been previously investigated and here we sought to determine their presence among different subtypes. Methods: We analyzed patients with stage I-III breast cancers between 2006 and 2012. Tumors were divided into three subtypes: hormone-receptor [ HR]-positive, HER2-negative (HR+,HER2-ve); HER2-positive and triple negative (TN). Hematoxylin and eosin stained sections were examined and the number of TAN per 10 high power fields (HPF, 40x) was recorded. Tumors with >1 TAN per 10 HPF were considered TAN-positive. Fisher’s exact test was used to test for independence between qualitative variables, and logistic regression models were applied for multivariate analysis. Results: A total of 133 patients were assessed for inclusion and 105 were analyzed (28 excluded on various criteria). Some 72 tumors (69%) were classified as HR+, HER2-ve, 15 (14%) as HER2+ and 18 (17%) as TN. Totals of 16 TN (88%), 8 HER2+ (53%) and 4 HR+, HER2-ve tumors (5%) were TAN+ (p<0.001), including 79% of HR-ve tumors (19 of 24), in contrast to 11% of their HR+ve counterparts (9 of 81) (p<0.001). HER2 expression (p=0.023) and tumor grade (p<0.001) were also associated with TAN positivity. On multivariate analysis, only HR negativity (OR 16.85; 95% CI 4.4-64.6, p=<0.0001) was associated with a higher likelihood of TAN positivity. Conclusions: TAN are present in most TN tumors. We found an absence of HR expression to be the only predictor of TAN positivity. These results raise the question as to whether TAN, as part of the tumor microenvironment, have a role in the aggressiveness and progression of TN tumors and thus warrant further investigation in this breast cancer subtype, particularly in relation to response to treatment and prognosis.     

Rare Breast Cancer Subtypes: Histological,Molecular, and Clinical Peculiarities

Breast cancer encompasses a collection of different diseases characterized by different biological and pathological features, clinical presentation, response to treatments, clinical behavior, and outcome. On the basis of cell morphology, growth, and architecture patterns, breast cancer can be classified in up to 21 distinct histological types. Breast cancer special types, including the classic lobular invasive carcinoma, represent 25% of all breast cancers. The histological diversity of breast carcinomas has relevant prognostic implications. Indeed, the rare breast cancer group includes subtypes with very different prognoses, ranging from the tubular carcinoma, associated with an indolent clinical course, to metaplastic cancer, whose outcome is generally unfavorable. New approaches based on gene expression profiling allow the identification of molecularly defined breast cancer classes, with distinct biological features and clinical behavior. In clinical practice, immunohistochemical classification based on the expression of human epidermal growth factor receptor 2 and Ki67 is applied as a surrogate of the intrinsic molecular subtypes. However, the identification of intrinsic molecular subtypes were almost completely limited to the study of ductal invasive breast cancer. Moreover, some good‐prognosis triple‐negative histotypes, on the basis of gene expression profiling, can be classified among the poor‐prognosis group. Therefore, histopathological classification remains a crucial component of breast cancer diagnosis. Special histologies can be very rare, and the majority of information on outcome and treatments derives from small series and case reports. As a consequence, clear recommendations about clinical management are still lacking. In this review, we summarize current knowledge about rare breast cancer histologies.     

Relationships between Reproductive Risk Factors for Breast Cancer and Tumor Molecular Subtypes

Background: Due to wide clinical differences in the various pathological types of breast cancer and also closeassociations between disease prognosis and molecular subtypes, relationships of the latter with traditional risk factorshave been suggested. Hence, the present study aimed to assess any associations. Methods: This bi-center cross-sectionalstudy was performed on 800 consecutive women with known breast cancer referred to two Comprehensive Cancer Centersin Tehran between 2006 and 2016. Baseline information related to reproductive risk profiles as well as pathologicaltumor diagnosis and molecular subtypes determined using immunohistochemical analysis by immune-staining forER, PR, and HER2 molecules were collected by reviewing hospital records. Results: Of 800 samples included forimmunohistochemical analysis, 314 (39.3%) were diagnosed as of Luminal A subtype, 107 (13.4%) as Luminal Bsubtype, 153 (19.1%) as HER-2 over-expressing, and 226 (28.3%) as triple negative. Among all reproductive riskfactors initially assessed, young age was associated with HER-2 over-expression, greater tumor size and a history ofabortion with the luminal B subtype, lower age at pregnancy with the luminal A subtype, and lower gravidity anda shorter duration of breastfeeding with the triple negative subtype. Conclusion: Each molecular subtype of breastcancer in our population may be associated with specific reproductive risk factors.     

Meta-analysis of the Correlation Between Schizophrenia and Breast Cancer

Purpose

To determine the correlation between schizophrenia and breast cancer (BC).

H—ras原癌基因在乳腺癌转移中的作用研究

目的 研究H－ras基因 在乳腺癌转移中的作用及作为预测乳腺癌转移潜能指标的价值。方法 采用免疫组织化学LSAS法观察76例乳腺癌、34例淋巴结转移灶和8例乳腺纤维腺瘤组织中p21蛋白、PCNA、CD44、ⅧRA g表达均呈正相关（r＝0．6337，P＜0．01；r ＝0．3044，P＜0．05）。p21蛋白阳性组肿瘤间质血管密度（IMVD）明显高于阴性组，2组比较有非常显著性差异（P＜0．01）。结论 p21蛋白表达与乳腺癌淋巴结转移密切相关；与CD44、IMVD联合检测可作为预测乳腺癌转移潜能敏感且准确的指标。