Ultrasonographic detection of metastatic axillary lymph nodes in breast cancer

Metastatic involvement of the axillary lymph nodes is the most important prognostic factor in breast cancer. Preoperative knowledge of lymph node status would be useful in planning the therapy for breast cancer. The aim of our study was to find how accurately metastatic lymph nodes can be detected with ultrasonography (US). Our study consisted of 63 breast cancer patients having 65 breast cancers. Their axillae were examined preoperatively with US (with a 7.5 Mhz linear-array transducer). 27.7% of these patients had metastatic axillary lymph nodes. With US we could detect 12 of these 18 axillary metastases. In 2 of our 6 false negative results only micrometastases were found on histological examination. In our study the sensitivity of US was 66.6%. There was only one axilla, in which nodes were detected with US, but on histological examination no metastases were found, thus giving a specificity of 97.9%. Our study indicates that in the axilla normal nodes are not visible with US.     

MRI鉴别诊断乳腺癌腋窝淋巴结转移

目的探讨MRI对乳腺癌患者腋窝淋巴结转移的鉴别诊断价值。方法分析经病理证实并行腋窝MR扫描的44例乳腺癌患者资料,分析MRI表现,包括淋巴结长径、短径、皮质厚度、ADC值、淋巴门情况、淋巴结边缘、周围脂肪间隙情况、DWI信号、强化方式及时间—信号强度曲线等,并绘制的ROC曲线分析淋巴结长径、短径、皮质厚度、ADC值对腋窝淋巴结转移的诊断效能。结果病理结果显示有淋巴结转移者24例(24/44,54.55%),无淋巴结转移者20例(20/44,45.45%),两者淋巴结长径、短径、皮质厚度、ADC值、淋巴门是否消失、淋巴结边缘、周围脂肪间隙、DWI信号、强化方式差异均有统计学意义(P均0.05)。淋巴结长径、短径、皮质厚度及ADC值的ROC曲线下面积分别为0.797、0.765、0.848、0.749。结论 MRI在鉴别乳腺癌腋窝淋巴结状态中有重要价值,皮质厚度大于0.54cm高度提示腋窝淋巴结转移。     

乳腺癌腋淋巴结微小转移灶与nm 23基因表达的研究

目的探讨乳腺癌患者腋淋巴结微小转移灶及其与nm 23表达的关系.方法对52例淋巴结常规检查阴性且病理报告无癌转移的乳腺癌患者腋淋巴结832枚及相应癌原发灶用抗上皮细胞膜(EMA)及nm23-H1单克隆抗体分别进行免疫组化染色.结果被检病例的 23.0%(12/52),淋巴结的 4.1%(34/832)存在淋巴结内微小转移癌.低分化组(40.0% , 8 /20)及肿瘤大于2.0cm (37.5% , 9/24)组转移率明显高于高分化组(12.0%, 4/32)及肿瘤小于 2 cm组 (10.7%, 3/28),差异具有显著性( P<0.0 1和P <0.05).51 .9%(27/52)的乳腺癌组织中nm23为阳性表达.淋巴结微小转移癌组nm23阳性表达率(25.0%,3/12)远低于非转移组(60.0%,24/40),差异具显著性(P < 0.05).结论采用单克隆抗体EMA探针及免疫组化技术检测常规病理检查难以确认淋巴结转移的乳腺癌淋巴结可以发现微小转移癌灶;乳腺癌转移早期nm23表达即下降.     

What constitutes adequate study of axillary lymph nodes in breast cancer?

This study was undertaken to determine the value of the clearing technique and multilevel sectioning of lymph nodes to aid in optimally examining axillary dissections for lymph node metastases. One hundred consecutive mastectomy specimens with axillary dissections were initially examined by our routine technique: examination of fat for lymph nodes by inspection and palpation and examination of one microsection from each lymph node. The remaining axillary tissue was then cleared using the technique of Durkin and Haagensen and each of the originally examined lymph nodes was resectioned at two additional deeper levels. In our routine examination, 2203 lymph nodes were found with 211 lymph nodes containing metastatic tumor. Clearing disclosed 412 additional lymph nodes, of which 17 contained metastatic tumor. The two additional microsections of lymph nodes revealed tumor in only two lymph nodes which were initially free of tumor. The extended study of the axilla did not add significantly to our routine examination.     

Micrometastasis to axillary lymph nodes and bone marrow in breast cancer patients

The axillary lymph nodes of 100 lymph node-negative breast cancer patients with known bone marrow status have been re-examined to explore the presence of micrometastasis in lymph nodes and the covariance of micrometastasis to bone marrow and lymph nodes. Nodes were serially sectioned at three intervals of 100 microm, followed by immunohistological (two sections) and haematoxylin-eosin staining (one section). Tumours were mainly T1 and T2, and the patients had on average 13 (4-22) lymph nodes removed. In two patients, micrometastasis was detected in one node. Another 25 patients possessed single positive immunostained cells mimicking tumour cells. These cells have been shown to be false positive cells by Perl and melanin staining. One patient had metastasis to several nodes missed by the original examination. Immunocytochemical detection of micrometastasis in bone marrow revealed 11 marrow-positive patients. This study has identified a low frequency of micrometastasis to lymph nodes, and no covariance with micrometastasis in the bone marrow was seen. Bone marrow micrometastasis may be an independent prognostic variable, separate from axillary node status.     

Predictors of positive axillary lymph nodes after sentinel lymph node biopsy in breast cancer.

OBJECTIVE: The purpose of this study was to determine the factors that predict the presence of metastasis in nonsentinel lymph nodes (SLN) when the SLN is positive. METHODS: A prospective database was analyzed and included patients who underwent SLN biopsy for invasive breast cancer from July 1997 to August 2000 (n = 442). One hundred (22.6%) patients had one or more positive SLNs, and were analyzed to determine factors that predicted additional positive axillary nodes. RESULTS: Of the 100 patients with a positive SLN, 40 patients (40%) had additional metastasis in non-SLNs. The only significant variables that predicted non-SLN metastasis were tumor lymphovascular invasion (P = 0.004), extranodal extension (P < 0.001), and increasing size of the metastasis within the SLN (P = 0.011). In analyzing just those patients who had lymphovascular invasion, extranodal extension, and a SLN metastasis > 2mm, 92% were found to have additional positive nodes. CONCLUSIONS: In patients with invasive breast cancer and a positive sentinel lymph node, lymphovascular invasion, extranodal extension, and increasing size of the metastasis all significantly increase the frequency of additional positive nodes.     

乳腺癌行腋窝淋巴结清扫规范、争议与共识

乳腺癌的有效治疗方法很多,但外科手术是公认的乳腺癌治疗的基础。手术成功与否的最根本标志是肿瘤手术区域的局部控制。腋窝淋巴结受累的程度是预测乳腺癌术后复发和生存,指导进一步个体化治疗的最为重要指标。规范的腋窝淋巴结清扫和病理检查对乳腺癌的治疗至关重要。术前判断存在腋窝淋巴结转移的乳腺癌病人,腋窝淋巴结清扫是乳腺癌手术的规范和要求。术前临床诊断无腋窝淋巴结转移（cN0）的早期乳腺癌病人,如果前哨淋巴结活检阴性可不做进一步的腋窝淋巴结清扫也已成为共识。对于前哨淋巴结1或2枚阳性的乳腺癌病人可以不行腋窝淋巴结的清扫的观点仍然存在争论。     

A strategic approach to the evaluation of axillary lymph nodes in breast cancer patients: analysis of 168 patients at a single institution

BACKGROUND: Preoperative evaluation of the axilla using fine-needle aspiration biopsy (FNAB) and/or intraoperative evaluation of the sentinel lymph nodes (SLNs) may significantly decrease the number of operative procedures required for staging or local control of the axilla in breast cancer patients. The purpose of this study was to examine and determine the number of operative procedures that could be excluded using both approaches. METHODS: A retrospective review of data was performed on 168 patients presenting with invasive clinical stage 1 to 3 breast cancer from March 2004 to March 2007. RESULTS: Of the 168 patients, 57 (34%) underwent ultrasound-guided FNAB for suspicious-appearing nodes. Of these 57 patients, 40 (70%) had a positive FNAB, and 16 (28%) had a negative FNAB. The FNAB was suspicious in 1 (2%) patient. One hundred twenty patients (71%) with a normal axillary ultrasound or with a negative or suspicious FNAB underwent SLN mapping, of which 29 (24%) had an intraoperative diagnosis of metastatic tumor. CONCLUSIONS: Preoperative evaluation of the axilla using ultrasound-guided fine-needle aspiration biopsy spared 24% of patients the cost and morbidity of undergoing SLN biopsy. SLN mapping, along with intraoperative evaluation of nodes, spared an additional 17% of patients from having to undergo a second operative procedure.     

Management of axillary and internal mammary lymph nodes in primary breast cancer]

Axillary lymph node dissection (ALND) is an effective staging procedure and is essential for local control of breast cancer. The regimen of the adjuvant systemic therapy is largely based on the number of nodes involved. There is as yet no evidence of survival benefit from axillary treatment by either surgery or radiotherapy, but this issue remains controversial. In general, the standard treatment of the axilla is surgical clearance of nodes from level I and II (partial ALND). If these nodes are involved, the clearance of level III nodes (complete ALND) is indispensable from the viewpoint of local control. Because a high rate of adverse events is observed, the extent of ALND should be determined by considering the balance between side effects and therapeutic benefit on a case-by-case basis. For the management of internal mammary nodes, most reports on randomized trials indicate that neither surgical treatment nor radiotherapy influences survival. However, the prognostic significance of internal mammary node status is high and a selected biopsy of lymph nodes with adenopathy should be considered for staging purposes. The significance of local control in this region is still controversial at present. About 30% to 40% of all invasive breast cancers are node positive. Thus, in most cases, the potential morbidity of ALND could be avoided if the status of the axillary nodes was ascertained with a less invasive procedure. The technique of sentinel lymph node biopsy may eventually prove to decrease the need for standard ALND. The randomized trial NSABP-B32 is ongoing and the results should indicate the clinical need for ALND.     

Predicting the status of the nonsentinel axillary nodes: a multicenter study

BACKGROUND: Sentinel lymph node (SLN) biopsy is a minimally invasive procedure that provides accurate nodal staging information. The need for completion axillary dissection after finding a positive SLN for breast cancer has been questioned. HYPOTHESIS: The presence of nonsentinel node (NSN) metastases in the axillary dissection specimen correlates with tumor size, the number of SLNs removed, and the number of positive SLNs. DESIGN: Prospective, multi-institutional study. PARTICIPANTS AND METHODS: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a nationwide study involving 148 surgeons. All patients underwent SLN biopsy, followed by level I/II axillary dissection. All SLNs were evaluated histologically at a minimum of 2-mm intervals. Immunohistochemical analysis using antibodies for cytokeratin was performed at the discretion of each participating institution. All NSNs were evaluated by routine histologic examination. RESULTS: An SLN was identified in 1268 (90%) of 1415 patients. Increasing tumor size was significantly correlated with increasing likelihood of positive NSNs: T1a, 14%; T1b, 22%; T1c, 30%; T2, 45%; and T3, 57% (P =.002, chi(2) test). The presence of positive NSNs was not significantly associated with the number of SLNs removed. Patients with more than 1 positive SLN were more likely to have positive NSNs than those with only 1 positive SLN (50% vs 32%; P<.001, chi(2) test). Increasing tumor size and the presence of multiple positive SLNs were also associated with the presence 4 or more positive axillary nodes. Multivariate analysis confirmed that tumor size and the number of positive SLNs were independent factors predicting the presence of positive NSNs. CONCLUSIONS: The likelihood of positive NSNs correlates with increasing tumor size and the presence of multiple positive SLNs. However, even patients with small primary tumors have a substantial risk of residual axillary nodal disease after SLN biopsy. These data will be helpful in counseling patients regarding the need for completion axillary dissection after a positive SLN is identified.     

乳腺癌新辅助化疗后腋窝淋巴结的变化

目的评价新辅助化疗对乳腺癌腋窝淋巴结的影响。方法45例Ⅱ、Ⅲ期乳腺癌接受新辅助化疗后手术(新辅助化疗联合手术组),根据体检、B超及钼靶像计数腋窝淋巴结总数和阳性、阴性淋巴结数,与未行新辅助化疗直接手术治疗的79例乳腺癌(直接手术组)比较,观察腋窝淋巴结的变化。结果新辅助化疗联合手术组检出腋窝总淋巴结和阳性淋巴结为(16.9±5.9)枚和(2.5±2.2)枚,显著低于直接手术组的(20.8±8.0)枚和(3.9±3.0)枚(t=-2.856,P=0.005;t=2.790,P=0.006),2组阴性淋巴结分别为(14.4±5.4)枚和(16.7±7.0)枚,无统计学差异(t=-1.904,P=0.055)。新辅助化疗联合手术组40例随访6~19个月,平均10个月;直接手术组67例随访7~21个月,平均12个月,2组各有4例复发。结论乳腺癌经新辅助化疗后行腋窝淋巴结清扫所检出的淋巴结总数和阳性淋巴结数减少。     

Diagnostic strategy for the assessment of axillary lymph node status in breast cancer

The nodal status in breast cancer is a major prognostic factor in terms of survival. It also plays a role in the therapeutic decision-making process. Therefore, the evaluation of lymph node involvement in breast cancer is imperative in establishing a personalized treatment scheme. The sentinel lymph node procedure has proved successful for small breast tumors (T1–T2), limiting axillary lymphadenectomy and its side effects without changing overall survival. Even so, a substantial number of women must undergo axillary lymphadenectomy during a second surgery when the analysis of the sentinel node discloses major nodal involvement. Imaging can improve patient selection, especially those who appear eligible for immediate axillary lymphadenectomy. Ultrasound is able to depict morphological abnormalities in the lymph nodes such as cortical thickening, peripheral vascularization, hilar infiltration and loss of the kidney-shaped appearance of a normal node. When ultrasound is negative, the risk of massive nodal involvement is limited, thus allowing the oncologist to take an approach with the sentinel lymph node procedure. Magnetic resonance imaging (MRI) can also be useful in detecting pathological lymph nodes, particularly with diffusion-weighted MRI sequence.     

Nonimage-guided fine needle aspiration biopsy of palpable axillary lymph nodes in breast cancer patients

We report the utility of office-based, nonimaged guided fine needle aspiration of palpable axillary lymph nodes in breast cancer patients. We examine the sensitivity and specificity of this procedure, and examine factors associated with a positive fine needle aspiration biopsy result. Although the utility of ultrasound-guided fine needle aspiration biopsy (FNA) of axillary lymph nodes is well established, there is little data on nonimage guided office-based FNA of palpable axillary lymphadenopathy. We investigated the sensitivity and specificity of nonimage-guided FNA of axillary lymphadenopathy in patients presenting with breast cancer, and report factors associated with a positive FNA result. Retrospective study of 94 patients who underwent office-based FNA of palpable axillary lymph nodes between 2004 and 2008 was conducted. Cytology results were compared with pathology after axillary sentinel node or lymph node dissection. Nonimage-guided axillary FNA was 86% sensitive and 100% specific. On univariate analysis, patients with positive FNA cytology had larger breast tumors (p = 0.007), more pathologic positive lymph nodes (p < 0.0001), and were more likely to present with a palpable breast mass (p = 0.006) or with radiographic lymphadenopathy (p = 0.002). FNA-positive patients had an increased presence of lymphovascular invasion (p = 0.001), higher stage of disease (p < 0.001), higher N stage (p < 0.0001), and higher rate of HER2/neu expression (p = 0.008). On multivariate analysis, radiographic lymphadenopathy (p = 0.03) and number of positive lymph nodes (p = 0.04) were associated with a positive FNA result. Nonimage-guided FNA of palpable axillary lymphadenopathy in breast cancer patients is an inexpensive, sensitive, and specific test. Prompt determination of lymph node positivity benefits select patients, permitting avoidance of axillary ultrasound, sentinel lymph node biopsy, or delay in receiving neoadjuvant therapy. This results in time and cost savings for the health care system, and expedites definitive management.