BRCA1在乳腺浸润性导管癌中的表达及其与Ki-67、p53的关系

目的：观察乳腺浸润性导管癌组织中BRCA1、Ki-67及p53的表达及其与临床病理特征之间的关系。方法采用EliVisionTMplus两步免疫组化方法,检测BRCA1、Ki-67及P53在60例乳腺浸润性导管癌组织的表达情况。结果①60例乳腺浸润性导管癌组织中,BRCA1的阳性率为60．0％（36／60）,Ki-67及 p53的阳性率分别为56．67％（34／60）、48．33％（29／60）;②BRCA1蛋白表达与患者发病年龄、临床分期、伴有腋淋巴结转移以及组织学分级有关（P＜0．05）,而与肿瘤大小无关（P＞0．05）;Ki-67表达与临床分期、淋巴结转移、组织学分级有关（P＜0．05）,与发病年龄、肿瘤大小无关（P＞0．05）;p53表达与肿瘤大小、临床分期、淋巴结转移、组织学分级相关（P＜0．05）,与发病年龄无关（P＞0．05）;③BRCA1表达与 Ki-67、p53均呈负相关（r1＝－0．577,P＜0．05,r2＝－0．504,P ＜0．05）,Ki-67与p53的表达呈正相关（r ＝0．375,P＜0．05）。结论联合检测BRCA1、Ki-67及p53对乳腺癌的早期诊断、恶性程度判定和预后监测有重要意义,可为乳腺癌的个体化治疗提供有效的指针。     

Ki-67在乳腺癌中的表达及其临床意义

目的 研究Ki 67在乳腺癌中的表达与临床病理特征的关系.方法 应用免疫组织化学方法检测120例女性乳腺癌患者中Ki-67、ER、PR、C-erbB-2的表达,分析Ki-67与ER、PR 、C-erbB-2、肿瘤大小、淋巴结转移情况、年龄、月经状况、病理组织学分级等临床病理特征的关系.结果 120例患者乳腺癌组织中Ki-67表达(-)6例(5％);Ki-67表达(+)36例(30％);Ki-67表达(++)31例(25.83％);Ki-67表达(+++)47例(39.17％).Ki-67表达与乳腺癌组织中C-erbB-2表达、肿瘤大小、淋巴结转移情况、患者年龄、月经状况之问差异无统计学意义(P＞0.05);与ER、PR受体表达、肿瘤组织学分级相关(P＜0.05).结论 Ki-67不能作为评估乳腺癌预后和指导临床治疗的重要指标.     

Survivin在乳腺癌中的表达及临床意义

目的 检测乳腺癌组织中Survivin的表达,结合10年预后随访结果,探讨Survivin的表达的临床意义.方法 采用免疫组织化学SP法及图像分析技术检测和分析60例乳腺癌、20例乳腺纤维腺瘤和20例正常乳腺组织中Survivin的表达,所有乳腺癌病例均做10年预后随访,并结合肿瘤的病理学特征和临床随访资料分析.结果 (1)60例乳腺癌中Survivin表达明显高于乳腺纤维腺瘤和正常乳腺组织(P＜0.01);(2)乳腺癌中Survivin表达与临床分期、腋淋巴结转移有关(P＜0.05);与患者年龄、肿瘤大小、组织学类型、病理分级均无关;(3)乳腺癌中Survivin与预后生存年限的表达呈显著负相关(P＜0.05).结论 Survivin在乳腺癌组织中表达上调,对乳腺癌发生和发展起重要作用.Survivin与乳腺癌的预后呈负相关.     

微型染色体维持蛋白2和Fas相关磷酸酯酶1与乳腺癌增殖和凋亡的关系

目的 探讨微型染色体维持蛋白2(MCM2)和Fas相关磷酸酯酶(FAP-1)的表达与乳腺癌增殖和凋亡的关系.方法 采用SP法检测60例乳腺癌及15例乳腺良性疾病中MCM2及FAP-1蛋白的表达水平,10例正常乳腺组织为对照组.结果 10例正常乳腺上皮、15例乳腺良性疾病、60例乳腺癌MCM2的阳性标记指数(LI)分别为6.6±1.1、14.7±3.2、44.7±4.3,各组间差异有统计学意义(P＜0.01);MCM2的阳性表达在乳腺癌TNM分期、不同组织学分级(Ⅰ、Ⅱ、Ⅲ)及淋巴结转移之间差异有统计学意义,呈升高趋势(P＜0.05);MCM2的LI均高于Ki-67的LI,MCM2和Ki-67在乳腺癌中的表达呈平行关系(P＜0.01).FAP-1的阳性表达率与乳腺癌的临床分期、病理分级及淋巴结转移性明显相关(P＜0.05);FAP-1在乳腺癌组织中的表达均显著高于正常组织和良性肿瘤.结论 MCM2、FAP-1在乳腺癌组织中的表达与乳腺癌的发生发展有密切联系,MCM2可能是更理想的细胞增殖标记物,FAP-1可能具有促进乳腺癌细胞增殖的作用.     

核仁蛋白、Ki-67表达对乳腺癌病人病情发生发展的影响分析

目的探讨乳腺癌组织中的核仁蛋白(PES1)、Ki-67蛋白表达与乳腺癌发生发展的关系。方法乳腺癌术后病理学标本及其癌旁组织标本85例,采用免疫组化染色技术检测两组标本中的PES1蛋白、Ki-67表达,按照乳腺癌病理学类型、组织学分级、临床分期、淋巴结转移情况进行分层分析。结果乳腺癌癌组织中的PES1蛋白、Ki-67蛋白阳性表达率分别为82.35%、64.71%,癌旁组织分别为37.65%、22.35%,两组比较差异有统计学意义(P0.05);乳腺癌组织中PES1蛋白、Ki-67蛋白表达无明显的相关关系(Spearman秩相关系数=0.175,P0.05);PES1蛋白在不同TNM分期、是否发生淋巴结转移的乳腺癌癌组织中表达差异有统计学意义(P0.05);Ki-67蛋白在不同组织学分级、是否发生淋巴结转移的乳腺癌癌组织中表达差异有统计学意义(P0.05)。结论 PES1、Ki-67表达对乳腺癌的发生及发展具有密切关系。     

三阴性乳腺癌组织乳腺癌易感基因1与表皮生长因子受体的表达及临床意义

目的探讨乳腺癌易感基因1(BRCA1)和表皮生长因子受体(EGFR)在三阴性乳腺癌组织中的表达、临床意义及相关性。方法收集51例三阴性乳腺癌标本,用高通量测序及免疫组化技术检测BRCA1突变和EGFR的表达,比较不同临床病理特征的三阴性乳腺癌患者癌组织中BRCA1突变与EGFR的表达。结果 BRCA1突变患者发病年龄较小、淋巴结转移率较高,临床分期较晚(P0.05);EGFR在肿块最大径2 cm、有淋巴结转移、临床分期Ⅲ～Ⅳ期患者组织中阳性表达率较高(P0.05);BRCA1与EGFR具有相关性(P0.05)。结论检测三阴性乳腺癌患者BRCA1及EGFR,对指导治疗及评价预后有重要的临床意义。     

RhoC、KAI1在原发性乳腺癌组织中的表达及意义

目的 探讨Ras homologous C(RhoC)、KAI1在乳腺癌组织中的表达及与临床病理特征的关系.方法 采用免疫组化方法,应用HPLAS-1000型彩色图像分析系统,检测45例乳腺良性疾病组织和75例乳腺癌组织中RhoC和KAI1的表达情况,并分析其与临床病理特征的关系.结果 RhoC蛋白在乳腺良性疾病组织和乳腺癌组织中表达的灰度值分别为(0.07±0.01)、(0.35±0.12),二者之间差异有统计学意义(P＜0.05).RhoC表达与乳腺癌淋巴结转移、TNM分期呈正相关(P＜0.05).KAI1蛋白在乳腺良性疾病组织和乳腺癌组织中表达的灰度值分别为(0.72±0.25)、(0.27±0.13),二者之间差异有统计学意义(P＜0.05).KAI1表达与乳腺癌淋巴结转移、TNM分期呈负相关(P＜0.05).RhoC、KAI1蛋白表达与患者年龄无相关性(P＞0.05).结论 RhoC、KAI1在乳腺癌发生、发展中发挥重要作用,RhoC和KAI1异常表达可能成为判断乳腺癌生物学行为的重要指标.     

乳腺癌组织中cIAP1、XIAP和caspase-3的表达及其临床意义

目的:探讨cIAP1、XIAP、caspase-3在乳腺癌组织中的表达与患者临床病理参数及预后的关系。方法:应用免疫组化法检测cIAP1、XIAP、caspase-3蛋白分子在99例乳腺癌、10例乳腺纤维腺瘤及6例癌旁正常乳腺组织中的表达,结合Kaplan-MeierPlotter数据库中的乳腺癌患者资料,分析3种蛋白与乳腺癌临床病理参数及其预后的关系。结果:免疫组化结果显示,乳腺癌组织中cIAP1、XIAP、caspase-3蛋白的表达水平均明显高于各自在正常乳腺组织中的表达(均P0.05),但3种蛋白表达水平在乳腺癌组织与乳腺纤维腺瘤组织中均无统计学差异,且在接受过与未接受过新辅助化疗乳腺癌患者的癌组织中也无统计学差异(均P0.05)。cIAP1的表达与患者的月经状态、年龄明显有关,而XIAP的表达与Ki-67的表达强度明显有关(均P0.05)。Kaplan-MeierPlotter数据库分析结果显示,cIAP1表达量与乳腺癌患者的无复发生存期关系不明显(P0.05),XIAP高表达乳腺癌患者的无复发生存期长于低表达乳腺癌患者,而caspase-3高表达乳腺癌患者的无复发生存期短于caspase-3低表达乳腺癌患者(均P0.05)。结论:cIAP1、XIAP和caspase-3的表达可能与乳腺癌的发生、发展密切相关,XIAP和caspase-3可作为评估乳腺癌预后的潜在指标。     

趋化因子受体5表达与乳腺癌临床病理特征及预后的相关性研究

目的 探讨趋化因子受体5(CCR5)在乳腺癌病灶和腋窝转移淋巴结中的表达及其与临床病理意义.方法 收集72例乳腺导管浸润癌及其腋窝淋巴结组织,50例乳腺纤维腺瘤组织,40例正常乳腺组织石蜡标本切片.采用免疫组化方法检测CCR5的表达情况;同时检测乳腺癌组织中C-erbB-2,p53,Ki-67,ER,PR的表达情况,并与临床病理资料进行统计学分析.结果 (1)乳腺癌组织中CCR5蛋白表达阳性率达84.72%(61/72),乳腺纤维腺瘤组织中表达阳性率较低(14%,7/50),正常乳腺组织中不表达CCR5;(2)乳腺癌CCR5表达与腋窝淋巴结转移呈正相关(X<'2>=4.982,P=0.026,r=0.305);(3)50例伴腋窝淋巴结转移的患者中,乳腺癌原发灶及转移淋巴结同时表达CCR5阳性者39例,具有较高的同源性;(4)乳腺癌CCR5表达与癌基因C-erbB-2之间呈低度正相关(P<0.05,r=0.291);(5)乳腺癌CCR5表达与患者年龄、绝经与否、肿瘤最大径、肿瘤分期等临床特征无关(均P>0.05);(6)乳腺癌CCR5表达与p53,Ki-67,ER,PR无关表达(均P>0.05).结论 CCR5在乳腺癌的发生、发展及腋窝淋巴结转移方面起一定作用;CCR5可间接作为预测乳腺癌腋窝淋巴结转移及预后判断的指标之一.     

乳腺癌组织中DNA修复酶MGMT、XRCC1的表达与临床预后因素的关系

目的 探讨乳腺癌组织中O6-甲基鸟嘌呤-DNA-甲基转移酶(MGMT)和X线修复交叉互补基因1(XRCC1)的表达及与临床预后因素的关系.方法 采用SP免疫组织化学法检测110例乳腺癌石蜡标本、19例纤维腺瘤石蜡标本及11例正常乳腺组织石蜡标本中MGMT和XRCC1蛋白的表达,分析其与临床预后因素的关系.结果 110例乳腺癌组织中MGMT阳性表达率为71.8%,其表达与乳腺癌患者的病理类型、浸润性导管癌的病理分化程度、淋巴结是否转移及ER表达明显相关(P＜0.05).XRCC1阳性表达率为30.9%,其表达与患者的肿瘤大小、浸润性导管癌的病理分化程度明显相关(P＜0.05).此外,MGMT与XRCC1的表达明显相关(P＜0.05),生存分析表明MGMT、XRCC1是影响生存期的因素(P＜0.05).结论 DNA修复基因MCMT及XRCC1是临床评估乳腺癌恶性程度、判断预后及制定治疗策略的病理指标之一.     

Family history of breast cancer,mammographic breast density and breast cancer risk: Findings from a cohort study of Korean women

BackgroundThis study investigated whether the association between family history of breast cancer in first-degree relatives and breast cancer risk varies by breast density.MethodsWomen aged 40 years and older who underwent screening between 2009 and 2010 were followed up until 2020. Family history was assessed using a self-reported questionnaire. Using Breast Imaging Reporting and Data System (BI-RADS), breast density was categorized into dense breast (heterogeneously or extremely dense) and non-dense breast (almost entirely fatty or scattered areas of fibro-glandular). Cox regression model was used to assess the association between family history and breast cancer risk.ResultsOf the 4,835,507 women, 79,153 (1.6%) reported having a family history of breast cancer and 77,238 women developed breast cancer. Family history led to an increase in the 5-year cumulative incidence in women with dense- and non-dense breasts. Results from the regression model with and without adjustment for breast density yielded similar HRs in all age groups, suggesting that breast density did not modify the association between family history and breast cancer. After adjusting for breast density and other factors, family history of breast cancer was associated with an increased risk of breast cancer in all three age groups (age 40–49 years: aHR 1.96, 95% confidence interval [CI] 1.85–2.08; age 50–64 years: aHR 1.70, 95% CI 1.58–1.82, and age ≥65 years: aHR 1.95, 95% CI 1.78–2.14).ConclusionFamily history of breast cancer and breast density are independently associated with breast cancer. Both factors should be carefully considered in future risk prediction models of breast cancer.     

早期乳腺癌保留乳房手术62例疗效评价

目的探讨早期乳腺癌保留乳房手术治疗疗效。方法回顾性分析1996～2004年经治的62例早期乳腺癌实施保乳手术治疗疗效。结果全部病人手术过程顺利,近期乳房外形保持良好。术后随访1～8年(平均2年),无局部复发、远处转移和死亡病例。无放疗后合并症。结论保乳手术治疗早期乳癌的近、远期疗效满意。术前严格掌握手术适应证,术后规范的综合治疗,是保乳手术获得良好疗效的保证。     

乳腺癌切除术后乳房再造

目的 探讨乳腺癌切除术后乳房再造的方法及时间.方法 总结30例不符合保乳条件的乳腺癌病例,乳房切除术后假体置人乳房再造16例,下腹部横行腹直肌肌皮瓣(TRAM瓣)乳房再造10例,背阔肌肌皮瓣乳房再造4例.其中即刻乳房再造27例,延期乳房再造3例.结果 16例假体置入乳房再造术后外观评价均为良,未出现术后并发症.10例TRAM瓣乳房再造术后发生皮瓣部分坏死2例,腹壁疝1例,术后外观评价7例为良.2例为较好,1例为差.4例背阔肌肌皮瓣再造术后外观评价为良.结论 乳房再造术是乳腺癌综合治疗不可忽视一部分,对于有强烈的保乳愿望,而又不符合保乳条件的患者,乳房再造术是一种较好的选择.即刻乳房再造优于延迟乳房再造.乳房再造的方法选择要因人而异.局部晚期乳腺癌患者可以选择性进行即刻乳房再造术.     

年龄相关的小叶复旧与乳腺癌

随着年龄增长,女性乳腺实质逐渐出现萎缩、退化甚至消失,这一生理性的过程称为年龄相关的小叶复旧.小叶复旧是不可逆的、系统性的个体化过程,与包括乳腺密度在内诸多乳腺癌危险因素密切相关,并被认为与乳腺癌的患病风险有关,但其具体机制尚不明确.     

乳腺癌与微卫星不稳定性的相关研究

目的 探索乳腺癌微卫星不稳定性(MSI)与临床特征的相关性.方法 收集60例乳腺癌组织标本,选择5个微卫星多态性标记(位点),DNA的提取,PCR扩增,电泳,EB显色后进行MSI分析.结果 乳腺癌MSI发生率为33.3%,正常乳腺组织MSI发生率为0,乳腺癌MSI与分化程度有关.结论 MSI是乳腺癌发生的早期分子生物学...     

Mammographic breast density and the risk of breast cancer: A systematic review and meta-analysis

ObjectivesMammographic density is a well-defined risk factor for breast cancer and having extremely dense breast tissue is associated with a one-to six-fold increased risk of breast cancer. However, it is questioned whether this increased risk estimate is applicable to current breast density classification methods. Therefore, the aim of this study was to further investigate and clarify the association between mammographic density and breast cancer risk based on current literature.MethodsMedline, Embase and Web of Science were systematically searched for articles published since 2013, that used BI-RADS lexicon 5th edition and incorporated data on digital mammography. Crude and maximally confounder-adjusted data were pooled in odds ratios (ORs) using random-effects models. Heterogeneity regarding breast cancer risks were investigated using I² statistic, stratified and sensitivity analyses.ResultsNine observational studies were included. Having extremely dense breast tissue (BI-RADS density D) resulted in a 2.11-fold (95% CI 1.84–2.42) increased breast cancer risk compared to having scattered dense breast tissue (BI-RADS density B). Sensitivity analysis showed that when only using data that had adjusted for age and BMI, the breast cancer risk was 1.83-fold (95% CI 1.52–2.21) increased. Both results were statistically significant and homogenous.ConclusionsMammographic breast density BI-RADS D is associated with an approximately two-fold increased risk of breast cancer compared to having BI-RADS density B in general population women. This is a novel and lower risk estimate compared to previously reported and might be explained due to the use of digital mammography and BI-RADS lexicon 5th edition.     

影响乳腺癌患者保乳手术边缘阳性因素的临床研究

目的探讨乳腺癌的临床病理学特征对保乳手术边缘阳性的影响。方法189例预行保乳手术术(BCT)的原发性乳腺癌患者,分析她们的临床特征(年龄,活检类型)和病理学特征(肿瘤大小,组织学类型,激素受体状态,HER2状态,和腋窝淋巴结状态)与阳性手术边缘的关系。结果189例患者中本组室心针肿脾物案例活检确诊79例,门诊或手术中切除活检确诊128例。61例手术边缘阳性(32.3%)。结论本研究的结果揭示:肿瘤直径大于2cm,腋窝淋巴结阳性PR阳性和年龄小于50岁是乳癌保乳手术边缘阳性的高危因素对1999年1月～2004年7月189例乳腺癌患者按受保乳手术进行回顾性分析,并总结手术切口边保阳性与临床特征病理案组但表现及激素受体状态的关系。     

Nutrition and breast cancer

The major risk factors for breast cancer are hormone-related, and the only well-established diet-related risk factors for breast cancer are obesity and alcohol consumption. Obesity increases breast cancer risk in postmenopausal women by around 30%, probably by increasing serum concentrations of bioavailable oestradiol. Moderate alcohol intakes increase breast cancer risk by about 7% per alcoholic drink per day, perhaps also by increasing oestrogen levels. Populations with high fat intakes generally have high rates of breast cancer, but studies of individual women have not confirmed an association of high fat diets with breast cancer risk. Phyto-oestrogens can affect hormone metabolism, but data on phyto-oestrogen consumption and breast cancer risk are inconsistent. Nutrition might affect breast cancer risk by altering levels of growth factors such as insulin-like growth factor-I. Current dietary advice should be to avoid obesity, limit alcohol intake, and maintain a varied diet.     

Interventional radiology in breast cancer

Molecular profiling of metastatic disease may greatly influence the systemic therapy recommended by oncologists and chosen by patients, allowing treatment to be more targeted. Comprehensive care of patients with advanced breast cancer now includes percutaneous image-guided biopsy if this has the potential to influence systemic treatment [1]. Interventional radiologists can contribute significantly to the care of patients affected by breast cancer, in diagnostic and supportive procedures and importantly also in treatment. Interventional radiologists carry out image guided percutaneous biopsies not only of the primary tumour but also of metastases. They insert percutaneous ports and tunnelled central venous catheters. They ablate painful bone metastases, and can treat or prevent pathological fractures. Most importantly they can ablate liver metastases in patients with limited or oligometastatic disease. The inhomogeneity and variety of cell populations in metastatic tumours from breast cancer, which is an important consideration in systemic therapy, is not an important consideration in the treatment of metastatic tumours using percutaneous ablative techniques, which are the major focus of this article. The treatment of primary tumours in the breast is also being explored, but is considered in its infancy at this stage.     

Preoperative (neoadjuvant) systemic treatment of breast cancer

Preoperative systemic treatment (PST) is a valid option not only for advanced breast cancer stages but also for operable breast cancer. We know that disease-free and overall survival after PST are equivalent to those after adjuvant therapy. Furthermore, PST is able to improve surgical treatment by increasing the rate of breast conservation surgery, which minimises psychological distress for patients fearing mastectomy. Response to PST is a predictor of long-term outcome and gives prognostic information after a short-term interval in contrast to adjuvant trials, which do not show their results until after a 5- to 10-year follow-up. More often, endocrine non-responsive tumours demonstrate a pathological complete response (pCR). Thus, PST can change the formerly bad prognostic marker into one that indicates a favourable prognosis if pCR is achieved by PST. If PST is performed outside clinical trials, anthracycline/taxane-based regimens should be used, especially in sequential prolonged schedules. The use of aromatase inhibitors in preoperative endocrine therapy in elderly postmenopausal patients with endocrine-responsive breast cancer yields a larger proportion of local response than tamoxifen. The duration of PST is not well established, but at least four cycles of chemotherapy should be administered and endocrine therapy needs a minimal time to show greatest benefit when given for at least 3-4 months . The concurrent use of chemotherapy and endocrine drugs did not show any benefit, even in endocrine-responsive tumours and should therefore be avoided. Sentinel node biopsy is a reasonable approach, but this technique should be reserved for experienced surgeons. PCR is the most important surrogate marker of PST, demonstrating an improved disease-free and overall survival. But even if pCR of the primary tumour is achieved, the detection of lymph node metastases is the most important prognostic factor, indicating a substantial risk of cancer recurrence. PST will lead to individualised (tailored) treatment in patients with primary breast cancer.