腋窝淋巴结阴性浸润性乳腺癌分子分型的表达及预后分析

  目的   探讨腋窝淋巴结阴性浸润性乳腺癌不同分子分型的分布,临床病理特征以及和预后的关系。   方法   回顾性分析183例该类乳腺癌患者的临床病理资料,对管腔上皮（Luminal）型、基底样（Basal-1ike）型和HER-2过表达（over-expression）型乳腺癌患者在年龄、肿瘤大小、临床分期和无瘤生存率（disease-free survival,DFS）、总生存率（overall survival,OS）方面进行统计分析。   结果   不同分子亚型乳腺癌在年龄、肿瘤大小、临床分期方面无显著性差异。Luminal、Basal-like、HER-2过表达型的复发率分别为3.9%（4/102）、20.4%（10/49）、6.3%（2/32）（P=0.002）;死亡率分别为2.0%（2/102）、6.1%（3/49）、3.1%（1/32）（P>0.05）。Ka-plan-Meier分析显示Basal-like型的DFS最低（P=0.002）,Basal-like型的OS较低（P=0.39）。Cox多因素比例风险模型分析显示分子亚型对DFS存在显著影响（P=0.001）。   结论   在腋窝淋巴结阴性浸润性乳腺癌患者中,不同分子亚型在年龄、肿瘤大小及临床分期方面无显著性差异,Basal-like型预后最差,分子分型是其独立预后指标。       

微血管密度与腋窝淋巴结阴性乳腺癌预后的关系

目的:探讨微血管密度(microvesseldensity,MVD)与腋窝淋巴结阴性乳腺癌(axillary-node-negativebreastcancer,ANNBC)预后的关系.方法:应用免疫组化方法检测ANNBC标本的MVD,并将所测值与部分预后指标的关系进行统计学分析.结果:MVD与ANNBC患者年龄、内分泌状况、激素水平无关(P均>0.05),而与ANNBC患者的无瘤生存率(disease-freesurvival,DFS)和总生存率(overallsurvival,OS)有明显关系(P分别=0.0012和0.0039).结论:MVD是腋窝淋巴结阴性乳腺癌的独立预后因素,可以用于筛选高危患者进行综合辅助治疗.     

不同分子分型1～2枚前哨淋巴结阳性乳腺癌免行腋窝淋巴结清扫的多因素分析

目的探讨不同分子分型1～2枚前哨淋巴结（sentinel lymph nodes,SLNs）阳性乳腺癌免行腋窝淋巴结清扫（axillary lymph node dissection,ALND）的临床病理因素,并为临床精准化提供依据。方法回顾性分析2009年6月至2018年6月274例就诊于内蒙古医科大学附属医院和内蒙古医科大学附属人民医院经病理证实的乳腺癌患者的临床病理资料,采用单因素及Logistic多因素分析筛选1～2枚SLN阳性但非前哨淋巴结（nonsentinel lymph node,NSLN）转移率较低的患者,同时明确其与不同分子分型的关系。结果274例1～2枚SLN阳性乳腺癌患者中,NSLN转移率为36.9%（101/274）。HER-2阳性（HR阳性）患者NSLN转移率最高, 占55.3%（21/38）;三阴性乳腺癌（triple negative breast cancer,TNBC）患者中NSLN转移率最低,占18.5%（5/27）。Luminal B型（HER-2阴性）乳腺癌患者的NSLN转移率明显高于Luminal A型（P=0.010）和TNBC患者（P=0.011）;HER-2阳性（HR阳性）乳腺癌患者的NSLN转移率明显高于Luminal A型（P=0.002）和TNBC患者（P=0.003）。 Logistic多因素分析显示,SLN转移数目（OR=4.022, 95%CI为2.348～6.889,P<0.001）,SLN检测（OR=3.846, 95%CI为1.541～9.600,P=0.004）,组织学分级（P<0.001）和分子分型（P=0.004）是1～2枚SLN阳性乳腺癌NSLN转移的独立影响因素。结论Luminal B型（HER-2阴性）和HER-2阳性（HR阳性）患者的NSLN阳性率较高,SLN转移数目、SLN检测、组织学分级和分子分型是NSLN转移的独立影响因素。      

不同分子分型乳腺癌患者预后与淋巴结转移率的相关性分析

[摘要] 目的: 探讨不同分子分型乳腺癌患者预后与Ⅱ、Ⅲ期乳腺癌淋巴结转移率的相关性。方法: 回顾性分析2011 年1 月至2016 年1 月在南京医科大学附属常州第二人民医院311 例确诊为Ⅱ、Ⅲ期乳腺癌并首选手术治疗的乳腺癌患者的临床资料,依据雌激素受体（ER）、孕激素受体（PR）、人类表皮生长因子受体-2（HER2）和Ki-67 增殖指数分为Luminal A型、Luminal B 型、HER2 过表达型和三阴型（TNBC）4 型。通过卡方检验分析不同分组间患者的临床特征;通过Kaplan-Meier 生存曲线评估腋淋巴结转移率（LNR）对各型乳腺癌患者预后的影响,以及相同LNR的不同分子分型的乳腺癌预后的差异,通过Spearman 相关分析LNR与Ki-67 增殖指数的相关性。结果: 不同分子分型在患者年龄、绝经情况、肿瘤大小、淋巴结状态及转移部位等临床特征差异无统计学意义（均P>0.05）。LNR为0 或>0.65 的4 组分子分型的无病生存时间（DFS）差异无统计学意义（χ2=3.581、2.808,均P>0.05）,LNR介于0.01~0.65 的4 组分子分型的DFS差异有统计学意义（χ2=24.366、8.169,均P<0.05）。LNR与Ki-67 增殖指数呈正相关（r=0.125,P<0.05）。多因素Cox 回归分析显示,乳腺癌患者预后与分子分型（RR=1.179,95%CI=1.023~1.358;χ2=5.165,P<0.05）、LNR（RR=1.137,95%CI=0.985~0.999;χ2=5.589,P<0.05）及Ki-67 增殖指数（RR=0.992,95%CI=1.022~1.264;χ2=5.623,P<0.05）有关。结论: LNR是Ⅱ、Ⅲ期乳腺癌预后的重要影响因素,相同LNR的不同分子分型预后差异显著,LNR与Ki-67 增殖指数呈正相关。     

腋窝淋巴结阴性乳腺癌复发的高危因素

１９２例腋窝淋巴绵阴性的Ⅰ，Ⅱ期乳腺癌就年龄，肿块大注，激素状态，组织学分级，病理状态和肿瘤标记物ＣＥＡ，ＣＡ１５－３进行单因素ｃｏｘ多元回归模型分析。结果显示：年龄３２例以下，激素受体阴性，组织学分级Ⅲ者均主危复发因素。病理切片见坏死或单核细胞增后，肿块切除不完全，ＣＥＡ，ＣＡ１５－３持续高浓度或治疗后再度升高者均提示复发机会较高。     

腋窝淋巴结阴性乳腺癌206例预后因素分析

目的探讨腋窝淋巴结阴性乳腺癌的临床特点、治疗方法及预后的影响因素。方法收集206例腋窝淋巴结阴性乳腺癌患者的临床病理资料,应用Kaplan-Meier法计算生存率,应用log-rank检验各组生存率,采用COX比例风险模型进行多因素分析。结果全组患者5年无复发生存率为83.5%,总生存率为95.6%。单因素分析显示,年龄（P=0.0137）、肿块大小（P=0.0002）、术后放疗（P=0.0176）、化疗（P=0.0104）、内分泌治疗（P=0.0091）是影响淋巴结阴性乳腺癌患者5年无病生存的因素;年龄（P=0.0113）、肿块大小（P=0.0375）、ER（P=0.0046）、PR（P=0.0275）是影响淋巴结阴性乳腺癌患者5年总生存的因素。多因素分析显示,肿块大小（P=0.002）是影响淋巴结阴性乳腺癌患者5年无病生存的独立预后因素。结论肿块大小是影响淋巴结阴性乳腺癌患者5年无病生存的独立预后因素。     

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.     

腋窝淋巴结阴性年轻乳腺癌患者的远期生存分析

摘 要：［目的］ 分析腋窝淋巴结阴性年轻乳腺癌患者的远期生存和影响预后的因素。［方法］ 1997年1月至2004年12月共手术治疗101例腋窝淋巴结阴性年龄≤35岁的乳腺癌患者。通过病例记录和系列随访收集患者的临床病理资料和生存情况。生存率计算采用Kaplan-Meier法,组间比较采用Log-rank检验,多因素预后分析采用Cox比例风险模型。［结果］ 中位随访12.18 年 (0.18~19.47年),全组共有3例患者失访,10例发生局部复发和/或区域淋巴结转移,10例远地转移（其中6例同时伴有区域复发）,11例第二原发恶性肿瘤,13例患者死亡。全组10年无病生存率、无疾病复发生存率、无远地转移生存率和生存率分别为70.0%、75.1%、83.4% 和 87.2%。淋巴结解剖个数≤10个是影响生存的因素(P=0.036)。肿瘤大小是影响疾病复发的独立因素(P=0.050),但对远地转移和生存均无影响。［结论］ 腋窝淋巴结阴性年轻乳腺癌患者的远期预后尚好,肿瘤大小和腋窝淋巴结解剖个数分别是疾病复发和生存的影响因素。     

早期乳腺癌腋窝淋巴结清扫和检测程度的临床意义

腋窝淋巴结清扫有重要的临床意义。但目前仍缺乏判断腋窝淋巴结清扫和检测是否彻底的统一标准；淋巴结阳性率及阳性个数随腋窝淋巴结清扫和检测数目的增加而增加，故淋巴结清扫和检测不彻底常导致低估腋窝淋巴结的转移状态，使一部分患者得不到应有的放疗，导致局部复发率相对升高；术后放疗是腋窝淋巴结清扫不彻底患者的有效挽救手段，可以达到与腋窝淋巴结彻底清扫相同的疗效。     

Sentinel lymph node biopsy without axillary dissection after an intraoperative negative histological investigation in 358 invasive breast cancer cases

BACKGROUND: Sentinel lymph node biopsy (SLNB) is an important treatment option for breast cancer patients, as it can accurately predict axillary status. Our previous study using dye with or without radioisotope showed the accuracy and sensitivity of SLNB to be 97% and 94%, respectively. Based on these results, axillary lymph node dissection (ALND) was eliminated starting in January, 1999 in patients with intraoperatively negative SLNB at our institution. The present study shows the results and outcomes of SLNB as a sole procedure for patients with invasive breast cancer. PATIENTS AND METHODS: Three-hundred-fifty-four patients and 358 cases of invasive breast cancer (4 bilateral breast carcinoma) treated with SLNB alone after an intraoperative negative SLNB were studied prospectively from January 1999 to December 2001. RESULTS: The number of the identified SLNs per case ranged from 1 to 8 (mean, 2.5). Of a total of 358 cases, 297 (83%) were treated with hormone therapy and/or chemotherapy, and 281 (78%) were treated with radiotherapy to the conserved breast (50 Gy+/-10 Gy boost), the axilla (50 Gy), or the both sites. After a median follow-up of 21 (range 6-42) months, no patient developed an axillary relapse. Four cases initially recurred in distant organs and one case in the conserved breast. CONCLUSIONS: Our results indicate that an intraoperative negative SLNB without further ALND may be a safe procedure when strict SLNB is performed. To better assess the safety, however, may require longer follow-up.     

Predictors of axillary lymph node metastasis in breast cancer: A systematic review

Aims

To review the established and emerging techniques in axillary lymph node prediction and explore their potential impact on clinical practice. To reliably identify patients in whom axillary lymph node surgery, including SLNB, can be safely omitted.

Methods

Searches of PubMed were made using the search terms “axilla” (or “axillary”), “lymph”, “node” and “predictor” (or “prediction”). Articles from abstracts and reports from meetings were included only when they related directly to previously published work.

Findings

There are numerous studies in which the predictive utility of biomarkers as determinants of axillary lymph node status have been investigated. Few of these have specifically addressed the attributes of the primary tumour which could offer much potential for the prediction of tumour metastasis to the axillary lymph nodes.

Conclusions

Currently, no single marker is sufficiently accurate to obviate the need for formal axillary staging using SLNB or axillary clearance.     

Clinical and pathologic factors predicting axillary lymph node involvement in breast cancer

The diagnosis of axillary disease remains a challenge in the management of breast cancer and is a subject of controversy. In 1998, the Japanese Breast Cancer Society conducted a study assessing axillary lymph node involvement in breast cancer. The study included (a) clinical assessment by pre-operative imaging modalities, (b) histologic assessment for peritumoral lymphatic invasion, (c) biologic assessment by gelatinolytic activity using film in situ zymography, and (d) sentinel lymph node (SLN) biopsy. Clinical assessments by CT, PET, and US as well as biologic assessment were limited in their ability to detect axillary lymph node disease, although these imaging techniques may be useful to exclude node-positive patients from the need for SLN biopsy. Histologic assessment for peritumoral lymphatic invasion was useful, particularly for detecting false-negative cases by SLN biopsy. Nevertheless, the utility of SLN biopsy in assessing axillary nodal status was confirmed. Axillary lymph node dissection (ALND) can be avoided in patients with a small tumor and a negative SLN. However, further studies will be required to investigate the value of SLN biopsy for predicting regional control and survival before it can replace routine ALND as the optimal staging procedure for operable breast cancer.     

Sentinel node biopsy to avoid axillary lymph node dissection in breast cancer

The role of sentinel node biopsy in breast cancer has increased over the last few years. Sentinel nodes can predict the status of all axillary lymph nodes precisely and select patients with negative nodes for whom axillary dissection is unnecessary. Many problems remain, such as the ideal injection technique, ideal agents, and ideal histological detection of sentinel node metastases, and must be addressed before sentinel node biopsy becomes the standard of care for patients with breast cancer.     

纳米炭对乳腺癌腋窝淋巴结示踪效果及其安全性的初步研究

目的探讨国产纳米炭混悬液对腋窝淋巴结的示踪效果及其安全性。方法2008年5月至2009年9月间对21例乳腺癌患者在术前采用纳米炭进行淋巴结示踪。患者年龄30～65岁,平均45．3岁。术前24～72h于乳晕周围分4点皮下均匀注射纳米炭混悬液共1ml。手术方式采用改良根治术5例,腔镜下乳房皮下腺体切除、腋窝淋巴结清除加假体植入术12例,乳腺癌局部扩大切除加腔镜腋窝淋巴结清除术4例。术后观察腋窝淋巴结的黑染情况并送病理检查。结果21例患者分别检出淋巴结14～32枚,平均每例21．5枚,共452枚。肉眼下黑染淋巴结共435枚,黑染率为96．3％（435／452）,其中明显黑染率为85．4％（386／452）。腋窝淋巴结无转移6例,有转移15例。有转移的淋巴结共45枚,均为明显黑染淋巴结,转移淋巴结黑染率为100％。经病理证实,未黑染的淋巴结均未出现癌转移。所有患者经8个月至2年的随访,均未出现复发转移及明显肝肾功能异常。有纳米炭残留的局部组织在术后1年行活组织检查,见乳腺组织间隙有较多的纳米炭颗粒沉集,但未见明显的炎症反应或组织变性。结论纳米炭混悬液经乳晕周围皮下注射后24～72h行腋窝淋巴结清除可达到良好的淋巴结示踪效果,有效避免转移淋巴结的漏检。残留体内的纳米炭无明显的毒副反应。纳米炭是一种安全可靠的腋窝淋巴结示踪剂。     

保留肋间臂神经在乳腺癌腋窝淋巴结清扫术中的应用

目的探讨Ⅰ、Ⅱ期乳腺癌改良根治术中保留肋间臂神经的临床价值。方法65例行Ⅰ、Ⅱ期乳腺癌改良根治术,保留肋间臂神经50例,切除15例,术后对患者进行随访观察。结果保留肋间臂神经50例中,术后患者上臂内侧及腋部皮肤感觉正常46例（92.0%）,感觉异常4例（8.0%）;切断肋间臂神经15例均有感觉障碍,两组比较差异有显著性（χ2=12.42,P〈0.001）。随访1年,50例均无肿瘤局部复发。结论在乳腺癌腋窝淋巴结清扫术中,保留肋间臂神经对改善患者术后生活质量具有一定的临床价值。     

Avoidance of axillary lymph node dissection in selected patients with node-positive breast cancer

Aims

Currently, it is standard practice to avoid ALND in patients with negative SLN, whereas this procedure is mandated for those with positive SLN. However, there has been some debate regarding the necessity of complete ALND in all patients with positive SLN. This review article discusses the issues related to eliminating the need for ALND in selected patients with positive nodes.

Methods

A review of the English language medical literature was performed using the MEDLINE database and cross-referencing major articles on the subject, focusing on the last 10 years.

Results

Currently, complete ALND is mandated in patients with SLN macrometastases as well as those with clinically positive nodes. It is not clear whether SLN biopsy is appropriate for axillary staging in patients with initially clinically positive nodes (N1) that become clinically node-negative (N0) after neoadjuvant chemotherapy. Although there is debate regarding whether ALND should be performed in patients with micrometastases in the SLN, it seems premature to abandon ALND in clinical practice. Moreover, it remains unclear whether it is appropriate to avoid complete ALND in patients with ITC-positive SLN alone.

Conclusions

In the absence of data from randomised trials, the long-term impact of SLN biopsy alone on axillary recurrence and survival rate in patients with SLN micrometastases as well as those with ITC-positive SLN remains uncertain. These important issues must be determined by careful analysis of the results of ongoing clinical trials.     

乳腺癌腋窝淋巴结声像图联合免疫组织化学与淋巴结转移的相关性研究

背景与目的：乳腺癌腋窝淋巴结转移对于乳腺癌患者的预后及治疗方案的选择有重要的指导意义。本研究旨在探讨乳腺癌腋窝淋巴结声像图表现联合免疫组织化学与腋窝淋巴结转移的相关性。方法：回顾性分析应用超声检出的366例乳腺癌患者共计728枚腋窝淋巴结的声像图表现,采用单因素分析、多因素logistic回归及受试者工作特征(receiver operating characteristic,ROC)曲线分析的方法,分别检验乳腺癌腋窝淋巴结皮质最大厚度、长短径之比、皮髓质之比和淋巴结血流特征,联合乳腺癌术后免疫组织化学结果,研究其与病理学腋窝淋巴结转移的相关性。结果：依据单因素分析,腋窝淋巴结皮质最大厚度、长短径之比、血流特征以及乳腺癌病灶p53的阳性表达率与淋巴结转移有关(P<0.05)。依据多因素分析及ROC分析,腋窝淋巴结皮质最大厚度是判定腋窝淋巴结转移的最佳指标。腋窝淋巴结皮质最大厚度大于3 mm的患者,其乳腺癌病灶的p53阳性表达率(42.78%)明显高于皮质最大厚度小于等于3 mm的患者(25.82%),差异有统计学意义(P<0.01)。结论：乳腺癌腋窝淋巴结声像图表现联合免疫组织化学评价腋窝淋巴结转移,对乳腺癌的临床诊疗方法选择具有重要价值。     

Follow-up of sentinel node negative breast cancer patients without axillary lymph node dissection.

BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the feasibility of sentinel lymph node biopsy in breast cancer patients at our institution and to report the follow-up status of node-negative patients with removal of only the sentinel node. METHODS: A total of 247 breast cancer patients underwent sentinel node (SN) mapping between June of 1996 and September of 2000. The SN was identified by using a combination of vital blue dye and a radiolabeled colloid. RESULTS: A SN was identified in 227 of 247 patients (91.9%). One hundred forty-five were SN negative, 82 were SN positive. All SN-positive patients underwent axillary dissection of level I and II, whereas 83 patients with a negative SN had SN biopsy only. Median follow-up of these patients at 22 months revealed no axillary recurrence; the morbidity resulting from SN biopsy was negligible. CONCLUSIONS: Although the follow-up is very short, SN biopsy only in node-negative breast cancer patients had no negative impact on the axillary failure rate and resulted in negligible morbidity.     

Whole sentinel lymph node analysis by a molecular assay predicts axillary node status in breast cancer

Background:

The one-step nucleic acid amplification (OSNA) assay is a rapid procedure for the detection of lymph node (LN) metastases using molecular biological techniques. The aim of this study was to assess the reliability of the whole sentinel lymph node (SLN) analysis by the OSNA assay as a predictor of non-SLN metastases.

Methods:

Consecutive 742 patients with breast cancer were enroled in the study. The association of non-SLN or ⩾4 LN metastases with clinicopathological variables was investigated using multivariate logistic analysis.

Results:

In total, 130 patients with a positive SLN who underwent complete axillary LN dissection were investigated. The frequency of non-SLN metastases in patients who were OSNA+ and ++ was 19.3% and 53.4%, respectively, and that in patients with ⩾4 LN metastases who were OSNA+ and ++ was 7.0% and 27.4%, respectively. The cytokeratin 19 (CK19) mRNA copy number (⩾5.0 × 10³; OSNA++) in the SLN was the most significant predictors of non-SLN metastases (P=0.003). The CK19 mRNA copy number (⩾1.0 × 10⁵) in the SLN was the only independent predictor of ⩾4 LN metastases (P=0.014).

Conclusion:

Whole SLN analysis using the OSNA assay could become a valuable method for predicting non-SLN and ⩾4 LN metastases.