Limitation in gamma probe localization of the sentinel node in breast cancer patients with large excisional biopsy

BACKGROUND: Radiolocalization and selective biopsy of the sentinel node to correctly predict the status of remaining lymph nodes may provide an alternative to axillary dissection in selected breast cancer patients with clinically negative lymph nodes. STUDY DESIGN: In a nonrandomized, multicenter clinical trial, gamma probe localization for lymphatic mapping and sentinel node biopsy along with axillary dissection was performed on 75 patients with invasive breast cancer and clinically negative lymph nodes. The accuracy of the sentinel node biopsy to correctly predict the status of the remaining axillary lymph nodes was established through standard pathologic investigation. RESULTS: A sentinel node was identified in 70 of 75 patients with a technical success rate of 93%. Of these 70 patients, 21 (30%) had axillary nodal metastases identified pathologically. Four of these 21 (19%) had sentinel nodes negative for metastases. All 4 false-negative patients had prior excisional biopsies. The false-negative group had a larger mean maximal biopsy dimension than the true-positive group. Eleven of the 21 patients with axillary metastases had a diagnosis made by core needle biopsy with no false negatives. CONCLUSIONS: The accuracy of the sentinel node biopsy in correctly predicting the status of remaining axillary lymph nodes may be limited in patients with large excision before radiolocalization of the sentinel node. Our findings suggest that excisional biopsy should be avoided prior to lymphatic mapping for sentinel node biopsy.     

前哨淋巴结检测在乳腺癌治疗中的意义

目的评价前哨淋巴结活检术 (sentinellymphnodebiopsy,SLNB)预测腋淋巴结肿瘤转移的准确性及其临床意义。方法使用专利蓝染色法和 /或99mTc标记的硫胶体示踪法对我院收治的81例乳腺癌患者进行前哨淋巴结活检。两种方法联合检测 3例前哨淋巴结 (sentinellymphnode ,SLN)均阴性者未行腋淋巴结清扫术。结果 81例患者SLN总检出率为 96 3% (78/81) ,总准确率为97 5 % ,总假阴性率 9 7%。 5 3例单纯染色法检出率为 92 5 % ,准确率 94 2 % ,假阴性率 15 8% ;2 8例99mTc示踪法和 /或染色法联合检测结果分别为 10 0 % ,10 0 %和 0。结论SLNB能够准确预测腋窝淋巴结的转移状况。两种方法联合检测为最佳。术前化疗对假阴性率可能有影响。     

临床腋淋巴结阴性乳腺癌前哨淋巴结研究

目的：探讨前哨淋巴结活检术（ｓｅｎｔｉｎｅｌ ｌｙｍｐｈ ｎｏｄｅ ｂｉｏｐｓｙ, ＳＬＮＢ）在乳腺癌治疗中的应用。方法：使用专利蓝和美蓝染色,对１９９９年９月～２００１年４月连续收治的１４５例临床查体腋窝淋巴结阴性乳腺癌病人行前哨淋巴结活检术。结果：ＳＬＮＢ成功率为９６．５％（１４０／１４５）,假阴性率为２３．５％,准确率为９１．４％。病人年龄、肿瘤最大径、肿瘤部位、注射染料类型及是否活检对成功率和假阴性率无影响。结论：ＳＬＮＢ能够准确预测腋窝淋巴结的转移状况,在缩小手术范围、减少术后并发症的同时,提高了腋窝淋巴结分期的准确性;美蓝与专利蓝均可成功确定ＳＬＮ。     

乳腺癌前哨淋巴结活检

目的 评价前哨淋巴结活检预测腋窝淋巴结有无肿瘤转移的准确性及其临床意义。方法 用^99m锝－硫胶体作为示踪剂,用γ探测仪导向,对70例临床分期为T1－2N0M0的乳腺癌患者进行前哨淋巴结活检,所有的患者均同时行腋窝淋巴结清扫,HE染色阴性的前哨淋巴结再切片,用CK8、CK19、KP－1行免疫组织化学染色。结果 70例患者中成功发现前哨淋巴结的有67例,发现率为95.7%（67／70）。前哨淋巴结的数量为1－5枚,平均每例1.6枚。非前哨淋巴结5－20枚,平均例12.3枚。67例前哨淋巴结活检成功的患者中,29例患者（43.3%）有腋窝淋巴结转移,其中前哨淋巴结有转移者24例（35.8%）,前哨淋巴结未发现转移而非前哨淋巴结有转移者5例（7.5%）。7例患者（10.4%）只有有淋巴结为阳性淋巴结,前哨淋巴结活检的准确性为100％。43例患者的65枚HE染色阴性一的前哨淋巴结,CK8及CK19免疫组织化学染色均为阴性。结论 前哨淋巴结检能较准确地预测腋窝淋巴结转移情况,对原发灶为T1的乳腺癌,前哨淋巴结活检的准确性为100％。同一层面切片行免疫组织化学染色并不能提高淋巴结微转移癌的发现率。     

Implication of intraoperative sentinel node imprint cytology for consent in the SNAC Trial

Background: Women randomized into the sentinel node biopsy‐only arm of the Sentinel Node versus Axillary Clearance Trial require axillary clearance if the sentinel node is unable to be identified, or if the sentinel node contains metastases. The aim of the present study was to determine the likelihood of immediate and delayed axillary clearance in patients in the trial when nodes were subjected to intraoperative imprint cytology. Methods: A prospective database for 400 patients with operable breast cancer was analysed to determine the likelihood of lymph node involvement according to tumour size. The ability to successfully remove a sentinel node and the accuracy of intraoperative imprint cytology of sentinel nodes was investigated. These data were used to predict the likelihood of patients proceeding to immediate or delayed axillary clearance. Results: The rate of lymph node involvement was 0%, 10%, 30%, and 53% in tumours measuring <5 mm, 6?10 mm, 11?20 mm and 21?30 mm, respectively. A sentinel node was identified in 95% of cases. In a series of 79 consecutive cases using intraoperative imprint cytology, 37% of sentinel nodes containing metastases were identified intraoperatively. The estimated likelihood of undergoing immediate axillary clearance therefore ranges from 5% for tumours <5 mm, up to 24% for tumours 21?30 mm. Similarly the likelihood of delayed clearance ranges from 0% to 32% depending on tumour size. Conclusions: It is possible to give detailed and accurate information to patients undergoing sentinel node biopsy about both the risk of lymph node involvement and the likelihood of requiring immediate or secondary axillary clearance.     

超声定位下可疑淋巴结取样在早期乳腺癌手术中的临床研究

目的 探讨早期乳腺癌更为合理的腋窝淋巴结处理方法,明确腋窝可疑淋巴结取样结合前哨淋巴结活检(SLNB)替代单纯SLNB时的假阴性率是否明显降低,为临床应用提供依据.方法 采用传统的腋窝淋巴结外科学分群方法,对符合入组条件的42例早期乳腺癌患者术前行B超引导下钩丝定位,术中行腋窝SLNB和定位的可疑淋巴结活检,再行全腋窝...     

T1期乳腺癌前哨淋巴结活检41例报告

目的 探讨前哨淋巴结活检术(sentinel lymph node biopsy，SLNB)在乳腺癌治疗中的应用。方法 使用美蓝染色，对2001年9月至2002年8月连续收治的41例T1期乳腺癌，临床检查腋窝淋巴结阴性的病人行前哨淋巴结活检术。结果 SLNB成功率87．8％(36／41)，假阴性率5．88％(1／17)，准确率97．2％(35／36)。结论 SLNB能够准确预测T1期乳腺癌腋窝淋巴结的转移情况，在缩小手术范围、减少术后并发症的同时，提高了腋窝淋巴结分期的准确性。     

The Role of Sentinel Lymph Node Biopsy with Blue Dye Alone in Breast Cancer Patients with Excisional Biopsy

Purpose : Sentinel lymph node biopsy (SLNB) appears to offer an excellent alternative method to routine axillary lymph node dissection for staging patients with breast cancer. The aim of this study is to evaluate the effect of excisional biopsy on identification and false negative rate of sentinel lymph node biopsy with blue dye alone in breast cancer patients with clinically negative axilla.

Material and Methods : From March 1998 to March 2003, 266 consecutive sentinel lymph node biopsies (SLNB) were performed using isosulfan blue dye alone. Patients were divided into two groups. One hundred and four patients (39.1%) had previously undergone an excisional biopsy (Group I); in 162 patients (60.9%), pre-operative diagnosis was obtained by either fine-needle aspiration biopsy (FNAB) or core biopsy (Group II). Following sentinel lymph node biopsy, all patients had axillary lymph node dissection (ALND). Data concerning patients, sentinel lymph nodes and the status of the axilla were collected and compared using Fisher’s exact test. A p value of less than 0.05 was considered statistically significant.

Results : The sentinel lymph node was successfully identified by blue dye in 94.3% (251/266) of patients. Mean lymph nodes removed from the axilla was 19 (range 11–36) and the mean number of sentinel nodes was 2 (range 1–5). The identification and false negative rate were unrelated to size, type or location of the tumour, or a previous surgical biopsy. Conclusions : SLNB with blue dye for evaluation of the axilla is a rapid and accurate technique that provides increased efficacy in the detection of lymphatic metastasis when careful pathologic evaluation with serial sections is performed. The risk-benefit analysis of lymphatic mapping with blue dye provides improvement in staging, with reduced morbidity and hospital stay, and the elimination of general anaesthesia. The technique may also be used safely and accurately in breast cancer patients with excisional biopsy.     

乳腺癌新辅助治疗前哨淋巴结处理原则

前哨淋巴结活检及新辅助治疗已成为乳腺癌综合治疗的重要措施，也是个体化治疗的重要体现。乳腺癌新辅助治疗具有较高的腋窝淋巴结控制率，如何在乳腺癌新辅助治疗病人中精准、高效实施前哨淋巴结活检引起越来越多的关注。新辅助治疗前后腋窝淋巴结状态的精准评估是实施前哨淋巴结活检的基础。对于新辅助治疗前腋窝淋巴结阴性的病人，推荐新辅助治疗后行前哨淋巴结活检。对于新辅助治疗前腋窝淋巴结阳性，新辅助治疗后淋巴结转阴的病人，需在双示踪、前哨淋巴结检出数≥3枚及阳性淋巴结靶向切除的前提下，进行前哨淋巴结活检，在我国医疗资源现状下，需结合示踪药物的可及性及技术条件，谨慎选择适宜病人。     

Sentinel Lymph Node Biopsy Performed After Neoadjuvant Chemotherapy is Accurate in Patients with Documented Node-Positive Breast Cancer at Presentation

Background The optimal strategy for incorporating lymphatic mapping and sentinel lymph node biopsy into the management of breast cancer patients receiving neoadjuvant chemotherapy remains controversial. Previous studies of sentinel node biopsy performed following neoadjuvant chemotherapy have largely reported on patients whose prechemotherapy, pathologic axillary nodal status was unknown. We report findings using a novel comprehensive approach to axillary management of node-positive-patients receiving neoadjuvant chemotherapy. Methods We evaluated 54 consecutive breast cancer patients with biopsy-proven axillary nodal metastases at the time of diagnosis that underwent lymphatic mapping with nodal biopsy as well as concomitant axillary lymph node dissection after receiving neoadjuvant chemotherapy. All cases were treated at a single comprehensive cancer center between 2001 and 2005. Results The sentinel node identification rate after delivery of neoadjuvant chemotherapy was 98%. Thirty-six patients (66%) had residual axillary metastases (including eight patients that had undergone resection of metastatic sentinel nodes at the time of diagnosis), and in 12 cases (31%) the residual metastatic disease was limited to the sentinel lymph node. The final, post-neoadjuvant chemotherapy sentinel node was falsely negative in three cases (8.6%). The negative final sentinel node accurately identified patients with no residual axillary disease in 17 cases (32%). Conclusions Sentinel lymph node biopsy performed after the delivery of neoadjuvant chemotherapy in patients with documented nodal disease at presentation accurately identified cases that may have been downstaged to node-negative status and can spare this subset of patients (32%) from experiencing the morbidity of an axillary dissection.     

乳腺癌腔镜前哨淋巴结活检83例临床分析

目的探讨染料法腔镜腋窝前哨淋巴结活检在乳腺癌中的可行性和临床意义。方法应用亚甲蓝染色法对83例Ⅰ、Ⅱ期乳腺癌行腔镜前哨淋巴结活检(ESLNB),然后行腔镜腋窝淋巴结清扫(EALND)。对获取的全部淋巴结行病理检查,评价前哨淋巴结检出率、准确率及假阴性率。结果83例中73例检出前哨淋巴结,检出率87.9%(73/83)。ESLNB准确率97.3%(71/73),灵敏性88.2%(15/17),特异性100.0%(56/56)。结论染料法腔镜腋窝前哨淋巴结活检临床可行,能够对早期乳腺癌进行准确分期,但体重指数高、肿瘤部位在内侧、术前肿瘤切除活检、腔镜技术欠熟练等是影响前哨淋巴结检出的主要因素。     

Removal of two sentinel nodes accurately stages the axilla in breast cancer

BACKGROUND: Assessment of lymph node status in breast cancer is still necessary for staging. Sentinel lymph node biopsy (SNB) may provide accurate staging with less morbidity than axillary clearance. The aim of this study was to assess the effect of the number of sentinel nodes removed on the false-negative rate. METHODS: Data were collected prospectively from 395 women undergoing SNB for breast cancer, between June 1995 and December 2001. All nodes that were hot and/or blue were removed and analysed. RESULTS: During this interval 136 patients who had SNB were lymph node positive. The median number of sentinel nodes removed was two (range one to five). The overall false-negative rate of SNB in these women was 7.1 per cent. If only one sentinel node had been removed, the false-negative rate would have been 16.5 per cent. The removal of more than two nodes had no effect on axillary staging in all but two women. CONCLUSION: In early breast cancer, when there were multiple sentinel nodes, removal of two sentinel nodes significantly reduced the false-negative rate compared with removal of one node. Removing more than two sentinel nodes did not significantly reduce the false-negative rate further.     

Sentinel lymph node biopsy after neoadjuvant chemotherapy in a patient with operable breast cancer

PURPOSE: This study was undertaken to assess the feasibility of performing a sentinel lymph node biopsy (SLNB) for a patient with operable breast cancer after undergoing neoadjuvant chemotherapy (NAC). METHOD: Between January 2002 and December 2003, women with primary breast cancer who had a breast tumor measuring larger than 3 cm in unilateral diameter were eligible for NAC. All patients who had completed NAC underwent lymphatic mapping with labeled (99m)Tc phytate on the day before surgery. Sentinel lymph node biopsy followed by a full axillary lymph node (AXLN) dissection (ALND) was performed in all patients. Sentinel lymph nodes (SLN) were sent for a frozen-section examination. RESULTS: The rate of SLN identification was 71%. Both the sensitivity and negative predictive value of SLNB were 100%. The false negative rate was 0%. When candidates for SLNB were restricted to patients with a breast tumor measuring less than 3 cm and clinically negative nodes after NAC, the rate of SLN identification increased to 93% from 71% while still maintaining the 0% false negative rate. CONCLUSION: Sentinel lymph node biopsy after NAC is therefore considered to be a feasible and accurate method to predict the AXLN status in patients who have a breast tumor measuring less than 3 cm in unilateral diameter and a clinically negative AXLN status at the time of surgery after NAC.     

γ探测仪在乳腺癌前哨淋巴结定位活检中的应用

目的:探讨γ探测仪在临床腋窝淋巴结阴性乳腺癌前哨淋巴结定位活检术(SLNB)中的临床应用价值.方法:利用99m锝-右旋糖酐(99mTc-DX)作为前哨淋巴结(SLN)示踪剂,应用γ探测仪定位对29例临床腋窝淋巴结阴性乳腺癌病人实施SLNB,随后进行常规腋窝淋巴清扫术,分析SLNB对腋窝淋巴结转移状态的预测价值.结果:本组SLN转移率为41.67%,非SLN转移率仅为22.54%,两者有明显差异(P＜0.001).在19例常规病理SLN阴性病人中,连续切片发现2例SLN微转移.在12例SLN癌转移中,5例(41.66%)SLN为惟一的转移部位.有1例SLN阴性病人"跳跃转移".本组SLN的敏感性为92.31%,特异性为94.12%,假阴性为7.69%,准确率达96.55%.结论:SLN能准确反映早期乳腺癌腋窝淋巴结转移状态,连续切片能提高SLNB的准确性.     

Lymphatic Mapping of the Breast: Locating the Sentinel Lymph Nodes

When the concept of sentinel lymph node biopsy was described in patients with melanoma, researchers quickly started to use lymphatic mapping techniques in breast cancer patients in an attempt to locate the sentinel node in the axilla. We have been performing mammary lymphoscintigraphy in this role for 6 years and have now studied 159 patients. Like others, we have found that most breast cancers (93%) have lymphatic drainage that includes the axilla, and we have found an average of 1.4 axillary sentinel nodes in these patients. Surgical biopsy of the axillary sentinel nodes accurately staged the node field in 96% of patients. We have also found, however, that the pattern of lymphatic drainage from the cancer site is unpredictable; and in 49% of patients lymphatic drainage occurred across the center line of the breast to axillary or internal mammary sentinel nodes. In more than half of our patients (56%) lymphatic drainage occurred to lymph nodes outside the axilla including the internal mammary (45%), supraclavicular (13%), and interpectoral and intramammary interval nodes (12%). These nodes are also sentinel nodes, and their presence indicates that a sentinel node biopsy procedure that stages only the status of the axillary lymph nodes has the potential to understage about half the patients with breast cancer. High quality lymphoscintigraphy allows accurate mapping of peritumoral lymphatic drainage in most patients with breast cancer. It is possible that in the future accurate nodal staging in each individual will involve biopsy of all sentinel lymph nodes, regardless of their location.     

Axillary Ultrasound Assessment in Primary Breast Cancer: An Audit of 653 Cases

Abstract: Axillary lymph node status is an important factor in determining the prognosis and treatment in patients with invasive breast cancer. The introduction of the sentinel lymph node biopsy technique in the axilla has significantly reduced the number of patients requiring an axillary clearance procedure. However, a proportion of patients will be found to have axillary metastases after a sentinel node biopsy and will then require a second axillary surgical procedure. A retrospective audit of 653 consecutive patients presenting with invasive breast cancer showed a preoperative diagnosis rate of axillary disease of 23% using axillary ultrasound and fine‐needle aspiration (FNA) together. We performed 232 axillary FNAs to diagnose 150 positive axillae. This avoided the need for a second operation in 150 women. The negative predictive value for axillary metastases using this technique was 79%. Overall accuracy was 84%.     

Axilloscopy and endoscopic sentinel node detection in breast cancer patients

Background: Sentinel node biopsy is a promising technique that allows the axillary status of breast cancer patients to be predicted with high accuracy. Reducing false negative results remains a major challenge for the improvement of this procedure. Furthermore, new techniques are required to achieve axillary clearing with less morbidity in cases of unsuccessful mapping or multicentric carcinoma. We analyzed whether axilloscopy and endoscopic sentinel node biopsy is a feasible procedure for visualization of the axillary space and resection of the sentinel node using endoscopic techniques. Methods: Following blue dye–guided lymphography and liposuction of the axillary fat, endoscopic axillary sentinel node biopsy was performed in 35 breast cancer patients. We then assessed the exposure of anatomical landmarks, the detection rate of the sentinel node, the false negative rate, and the accuracy of consecutive axillary clearing. Results: In almost every case, an excellent anatomical orientation was achieved. The detection rate for the sentinel node was 83.3%. In one case, the sentinel node did not reflect the status of the residual axilla. A mean number of 17.1 lymph nodes was harvested at consecutive axillary clearing. Conclusions: Axilloscopy and endoscopic sentinel node biopsy, following liposuction of the axillary fat, is a feasible procedure that allows identification and minimally invasive resection of the sentinel node with high accuracy. The endoscopic approach might help to minimize the pitfalls of sentinel node biopsy by visualizing the axillary space. In future, it may become a technique that enables minimally invasive axillary clearing when complete lymphadenectomy is required. Received: 7 April 1999/Accepted: 16 December 1999/Online publication: 17 April 2000     

Intraoperative Imprint Cytologic Assessment of the Sentinel Node for Early Breast Cancer

Abstract An increasing number of patients are undergoing sentinel node biopsy alone for axillary staging of early breast cancer. A reliable method for evaluating the status of the sentinel node intraoperatively would allow patients with sentinel node metastases to undergo immediate rather than delayed axillary clearance. Sentinel nodes in 53 consecutive patients were examined by intraoperative imprint cytology. When compared with subsequent analysis by hematoxylin-eosin staining and immunohistochemistry, the accuracy of imprint cytology for the detecting nodal metastases was 81.1%; the false negative rate was 47.0%, and there were no false positives. Results were made available to the operating surgeon within a mean time of 25 minutes. All but one of the false negatives involved micrometastatic deposits of less than 0.1 mm. Intraoperative imprint cytologic examination of the sentinel node is a useful technique that can be performed efficiently and without loss of nodal tissue for subsequent analysis. With the use of this technique, more than 50% of lymph node-positive patients would potentially be spared a second operation.     

Sentinel Node Biopsy: Standard of Care

Abstract: Sentinel lymph node biopsy (SLNB) is a less invasive alternative to axillary lymph node dissection (ALND) for staging breast cancer. In appropriate women, this procedure can stage the axilla with less extensive surgery and fewer complications. Sentinel node status is accurate in predicting axillary status based on single institutional experiences and confirmed by large multi‐center trials. Non‐sentinel nodes are involved very rarely if the sentinel node is tumor‐free. SLNB enables intense examination of a single lymph node. However, the use of special stains to detect micrometastases is of uncertain clinical significance and is the subject of large trials. Early follow‐up from the John Wayne Cancer Institute experience demonstrates excellent outcome for patients with either micrometastases or tumor‐free nodes. Results from techniques with either blue dye or radioisotope colloid tracer and injection locations at peri‐areolar, peritumoral, or subcutaneous sites are similar. These findings support the biological concept of a single (or very few) sentinel nodes for the entire breast. The sentinel node is more predictive of axillary status than any other tumor prognostic factor. Axillary lymph node dissection is unlikely to reveal nodal metastases when the sentinel node is tumor‐free, and in such cases there is no reason to perform a completion axillary node dissection. Sentinel node biopsy alone without axillary lymph node dissection should now be the standard of care for most clinically node‐negative women with breast cancer.     

Identification and evaluation of axillary sentinel lymph nodes in patients with breast carcinoma treated with neoadjuvant chemotherapy

Sentinel lymph node (SLN) biopsy has been shown to predict axillary metastases accurately in early stage breast cancer. Some patients with locally advanced breast cancer receive preoperative (neoadjuvant) chemotherapy, which may alter lymphatic drainage and lymph node structure. In this study, we examined the feasibility and accuracy of SLN mapping in these patients and whether serial sectioning and keratin immunohistochemical (IHC) staining would improve the identification of metastases in lymph nodes with chemotherapy-induced changes. Thirty-eight patients with stage II or III breast cancer treated with neoadjuvant chemotherapy were included. In all patients, SLN biopsy was attempted, and immediately afterward, axillary lymph node dissection was performed. If the result of the SLN biopsy was negative on initial hematoxylin and eosin-stained sections, all axillary nodes were examined with three additional hematoxylin and eosin sections and one keratin IHC stain. SLNs were identified in 31 (82%) of 38 patients. The SLN accurately predicted axillary status in 28 (90%) of 31 patients (three false negatives). On examination of the original hematoxylin and eosin-stained sections, 20 patients were found to have tumor-free SLNs. With the additional sections, 4 (20%) of these 20 patients were found to have occult lymph node metastases. These metastatic foci were seen on the hematoxylin and eosin staining and keratin IHC staining. Our findings indicate that lymph node mapping in patients with breast cancer treated with neoadjuvant chemotherapy can identify the SLN, and SLN biopsy in this group accurately predicts axillary nodal status in most patients. Furthermore, serial sectioning and IHC staining aid in the identification of occult micrometastases in lymph nodes with chemotherapy-induced changes.