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。     

预测乳腺癌腋窝淋巴结转移的研究进展

19世纪，乳腺癌被认为是局部病变，沿淋巴管转移扩散，且遵循逐级转移即从第一站淋巴结转移到第二站淋巴结，然后再转移到全身的规律。Halsted根治术就是依据这个理论设计的手术方式。直到20世纪60年代Fisher提出乳腺癌是全身性疾病，在病程的早期即可发生全身转移。乳腺癌局部病变的理论便为全身性疾病的理论所替代。并且，依据预后因素用“预后好”或“预后差”的乳腺癌替代“早期”或“晚期”乳腺癌。     

乳腺癌腋窝淋巴结转移规律数学模型的建立

目的：建立一个数学模型，对不完全腋窝淋巴结清扫的患者应用Ⅰ级淋巴结的信息预测Ⅱ、Ⅲ级淋巴结的状态，以指导术后辅助治疗。方法：连续收集９０例女性乳腺癌初治患者行全腋窝淋巴结清扫术的资料，全组共被切出１７９３枚淋巴结，平均每例１９．９２枚；Ⅰ、Ⅱ和Ⅲ级分别为８５６（４７．７４％），６２０（３４．５８％），３１７（１７．６８％）枚，Ⅰ级淋巴结平均为９．５１枚。采用ＳＰＳＳ软件行Ｌｏｇｉｓｔｉｃ多元回归判     

乳腺癌腋窝淋巴结转移的多因素分析

目的:研究乳腺癌腋窝淋巴结转移与年龄、民族、初潮年龄、第一胎生育年龄、绝经、绝经年龄、病程、哺乳时间、妊娠次数、肿瘤部位、肿瘤大小（B超、钼靶、MRI分别测值）、病理分型、雌激素受体（ER）、孕激素受体（PR）、C-erbB-2基因表达之间的关系及规律,为乳腺癌手术中腋窝淋巴结清扫术的指征提供理论依据。方法:回顾性分析356例乳腺癌患者的临床资料。结果:腋窝淋巴结转移228例（64%）,无转移128例（36%）;腋窝淋巴结转移与第一胎生育年龄、妊娠次数、哺乳时间、病程、肿瘤大小(B超、钼靶、MRI)、肿瘤部位、病理类型相关（P<0.05）,P值分别为0.007、0.005、0.006、0.022、（0.001、0.000、0.020）、0.009、0.000。结论:腋窝淋巴结的转移受多种因素影响。     

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。      

乳腺癌腋窝淋巴结转移的MRI评价

乳腺癌是女性最为常见的恶性肿瘤之一,腋窝淋巴结的转移情况对疾病分期、治疗手段的选择以及预后判断具有重要意义。现阶段临床多采用超声或前哨淋巴结活检来评价腋窝淋巴结有无转移,但上述方法存在不足之处或伴随并发症的发生。磁共振成像近年来被越来越多地运用于乳腺癌腋窝淋巴结转移的无创诊断。本文将回顾通过MRI直接评价乳腺癌腋窝淋巴结转移（而非通过肿瘤本身的MRI相关特征预测腋窝淋巴结转移）的文献,并将MRI的相关特征用于诊断乳腺癌腋窝淋巴结转移的准确性进行综述。本文发现目前的研究结果之间存在差异,使用MRI多参数联合可提高诊断准确性,并且影像组学的出现也为诊断带来了新的机遇。     

腋窝淋巴结阴性浸润性乳腺癌的分子分型及预后观察

目的探讨腋窝淋巴结阴性浸润性乳腺癌患者的分子分型及其预后情况。方法回顾性分析2006年12月至2009年6月间180例腋窝淋巴结阴性浸润性乳腺癌的临床病理资料,并按照雌激素受体(ER)、孕激素受体(PR)及人类表皮生长因子受体-2(HER-2)的检测结果将其分为管腔上皮(Luminal)型、基底样(Basal-like)型及HER-2过表达(over-expression)型,观察不同分型乳腺癌在不同年龄、肿瘤大小及分期中的表达及预后情况。结果 180例腋窝淋巴结阴性浸润性乳腺癌患者中,Luminal型、Basal-like型、HER-2过表达型分别占54.4%(98/180)、27.8%(50/180)和17.8%(32/180)。Luminal型、Basal-like型、HER-2过表达型在不同年龄、肿瘤大小及临床分期中的表达差异无统计学意义(P>0.05)。Basal-like型患者术后36和60个月的转移率分别为14.0%和36.0%,高于Luminal型的3.1%、20.4%及HER-2过表达型的6.3%、21.9%,差异有统计学意义(P<0.05)。Basal-like型患者术后60个月的死亡率为24.0%,高于Luminal型(10.2%)及HER-2过表达型(15.6%),HER-2过表达型患者术后60个月的死亡率高于Luminal型,差异有统计学意义(P<0.05)。结论腋窝淋巴结阴性浸润性乳腺癌的分子分型以Lumina1型最为常见,Basal-like型与HER-2过表达型构成比较低,其中Basal-like型患者预后较差,其次为HER-2过表达型患者。     

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。     

乳腺癌术后对侧腋窝淋巴结转移7例分析

乳腺癌术后对侧腋窝淋巴结转移７例分析龚益平乳腺癌转移至对侧腋窝淋巴结较为罕见，１９８１作者单位：湖北省肿瘤医院（４３００７９武汉市洪山区卓刀泉南路１６号）年—１９９６年间，我们收治７例，占同期住院乳腺癌病人总数的０．２３％，现报道并分析如下。１临床资...     

左侧乳腺癌右腋窝淋巴结转移2例

例1,女,40岁。1994年2月发现左侧乳房有核桃大小肿块,不红不痛,无发热,边界不清。4月20日住院治疗,查体:左乳头抬高,无溢液,皮肤无改变。乳房内上限触及5cm×5cm肿块,质中,界限不清,与胸大肌无粘连。左腋窝触及肿大淋巴结2枚。右乳房及液窝淋巴结无异常。X光片示肺部正常。诊断:左侧乳腺癌(Ⅲ期)。行改良式乳癌根治术。     

Factors influencing axillary lymph node metastasis in invasive breast cancer

Purpose: To explore the relationship between auxiliary lymph node metastasis and clinical features, andto identify the factors that affect metastasis occurrence. Methods: A total of 164 cases of primary breastcancer were selected to investigate features such as age, concomitant chronic disease and pathologic diagnosis.Immunohistochemistry was used to detect the expression of the estrogen receptor (ER) and CerbB-2. Logisticregression was employed to analyze the factors that affect the incidence of lymph node metastases. Results: Theincidence of lymph node metastases was 46.3% among elderly patients with breast cancer. Based on logisticregression, chronic disease, scale of tumor, age, and ER expression affected the occurrence of lymph nodemetastases; the ORs were 3.05, 2.18, 0.34, and 3.83, respectively. Between different pathologic diagnoses andthe risk factors, the OR scores were 12.7 and 8.02, respectively, for aggressive ductal carcinoma and aggressivelobular carcinoma auxiliary lymph node metastases. Conclusion: The incidence of lymph node metastases isaffected by chronic disease, scale of tumor, age, ER expression and pathologic diagnosis.     

Proteomic profiling of primary breast cancer predicts axillary lymph node metastasis

To determine if protein expression in primary breast cancers can predict axillary lymph node (ALN) metastasis, we assessed differences in protein expression between primary breast cancers with and without ALN metastasis using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Laser capture microdissection was performed on invasive breast cancer frozen sections from 65 patients undergoing resection with sentinel lymph node (SLN) or level I and II ALN dissection. Isolated proteins from these tumors were applied to immobilized metal affinity capture (IMAC-3) ProteinChip arrays and analyzed by SELDI-TOF-MS to generate unique protein profiles. Correlations between unique protein peaks and histologically confirmed ALN status and other known clinicopathologic factors were examined using ANOVA and multivariate logistic regression. Two metal-binding polypeptides at 4,871 and 8,596 Da were identified as significant risk factors for nodal metastasis (P = 0.034 and 0.015, respectively) in a multivariate analysis. Lymphovascular invasion (LVI) was the only clinicopathologic factor predictive of ALN metastasis (P = 0.0038). In a logistic regression model combining the 4,871 and 8,596 Da peaks with LVI, the area under the receiver operating characteristic curve was 0.87. Compared with patients with negative ALN, those with > or =2 positive ALN or non-SLN metastases were significantly more likely to have an increased peak at 4,871 Da (P = 0.016 and 0.0083, respectively). ProteinChip array analysis identified differential protein peaks in primary breast cancers that predict the presence and number of ALN metastases and non-SLN status.     

Significance of axillary lymph node metastasis in primary breast cancer.

PURPOSE: Axillary lymph node status is the single most important prognostic variable in the management of patients with primary breast cancer. Yet, it is not known whether metastasis to the axillary nodes is simply a time-dependent variable or also a marker for a more aggressive tumor phenotype. The purpose of this study was to determine whether nodal status at initial diagnosis predicts outcome after relapse and therefore also serves as a marker of breast cancer phenotype. PATIENTS AND METHODS: Survival experience after first relapse in 1,696 primary breast cancer cases was analyzed using Cox proportional hazards regression. The following explanatory variables and their first-order interactions were considered: number of axillary lymph nodes involved (zero v one to three v four or more), hormone receptor status (any estrogen receptor [ER] negativity v ER negativity/progesterone receptor positivity v other ER positivity), primary tumor size (< 2 cm v 2 to 5 cm v > 5 cm), site of relapse (locoregional v distant), disease-free interval (< 1.5 years v 1.5 to 3 years v > 3 years), adjuvant endocrine therapy (none v any), adjuvant chemotherapy (none v any), and menopausal status (pre-, peri-, or postmenopausal). RESULTS: Axillary lymph node status, site of relapse, and hormone receptor status were all highly significant as main effects in the model. After adjustment for other variables, disease-free interval alone was only modestly significant but interacted with nodal status. After disease-free interval, hormone receptor status, and site of relapse were accounted for, survival after relapse was poorer in node-positive cases, when compared with node-negative cases. The hazard ratios for patients with one to three and four or more involved nodes were 1.2 (95% confidence interval [CI], 0.8 to 1.9) and 2.5 (95% CI, 1.8 to 3.4), respectively. CONCLUSION: Patients with four or more involved nodes at initial diagnosis have a significantly worse outcome after relapse than node-negative cases, regardless of the duration of the disease-free interval. We conclude that nodal metastasis is not only a marker of diagnosis at a later point in the natural history of breast cancer but also a marker of an aggressive phenotype.     

以腋窝淋巴结转移为首发症状的隐匿性乳腺癌临床分析

目的:探讨伴腋窝转移的隐匿性乳腺癌(OBC)诊断、治疗及预后.方法:回顾性分析2000-03-2004-07收治的24例伴腋窝转移的OBC患者的临床资料.结果:24例术前触诊、钼钯和超声检查均未发现同侧乳腺确切肿物,术中病理示淋巴结转移癌(乳腺来源可能性大).行同侧乳房切除加腋窝淋巴结清除术(术中剖开乳腺腺体9例发现原发灶),其3、5年总生存率分别为79.2%和66.7%.腋淋巴结转移数目<4者13例和≥4者11例,其3、5年生存率分别为84.6%、76.9%和72.7%、54.5%.结论:OBC应选择以同侧乳房切除加腋窝淋巴结清除术为主的综合治疗,特别是腋淋巴结转移数≥4者,治疗应更积极.     

Therapeutic options for contralateral axillary lymph node metastasis in breast cancer

Contralateral axillary lymph node metastasis (CAM) in breast cancer is rare, and the reason is unclear. CAM may be found at the time of primary breast cancer diagnosis or following primary tumor treatment. CAM staging and treatment methods are controversial. Hence, we summarized the features of CAM patients and explored the therapeutic options. We report the case of an 82-year-old woman with right breast cancer accompanied by CAM. The records of breast cancer patients with CAM in PubMed (January 2000-May 2020) were also reviewed. After undergoing comprehensive treatments (neoadjuvant chemotherapy, surgery, radiotherapy, endocrine therapy, and targeted therapy), no signs of recurrence and metastasis were noted during the 25-month follow-up. Overall, 17 studies (36 patients) were selected for the review, of which 15 had synchronous CAM and 21 had metachronous CAM. Nineteen of 22 patients had histologic grade 3. Forty percent (12/30) had ≥4 positive lymph nodes. Among these 36 patients, 9 had triple-negative breast cancers, and 9 were human epidermal growth factor receptor 2 positive. Among the 30 patients staged, 6 (20%) were in stage I; 7 (23.33%), stage II; and 17 (56.67%), stage III. Two patients received systemic therapy, while one received an unknown treatment. The remaining 33 patients all received local treatment (surgery or radiotherapy). The survival time of synchronous and metachronous CAM patients was 12-72 months with the death rate of 1/7 and 12-144 months with that of 3/12, respectively. CAM may be a regional manifestation rather than a distant metastasis. Comprehensive treatment, including surgery and radiotherapy, may provide better control.     

前哨淋巴结活检术检测乳腺癌腋窝淋巴结转移的效果评价

区域淋巴结是否转移是影响乳腺癌患者预后的独立因素。临床已证实,对于腋窝淋巴结阴性乳腺癌患者,行常规腋窝淋巴结清除术(axillary lymph node dissection,ALND)无任何治疗意义,而且可引起许多并发症。乳腺癌前哨淋巴结