An axillary recurrence of breast cancer following a negative sentinel lymph node biopsy

Abstract: In many parts of the United States, lymphatic mapping and sentinel lymph node biopsy has almost replaced axillary lymph node dissection (ALND) as the axillary staging procedure of choice for small, clinically node-negative breast cancers. However, the long-term outcome of patients undergoing a sentinel lymph node biopsy as the only axillary procedure in patients with tumor-free sentinel nodes remains to be determined. We present the first reported case of axillary recurrence in a patient with breast cancer following a tumor-negative sentinel lymph node biopsy. Whether sentinel lymph node biopsy can replace ALND in the management of patients with early breast cancer remains to be answered.     

Clinicopathologic analysis of sentinel lymph node mapping in early breast cancer

Axillary nodal status is the most significant prognosticator for predicting survival and guiding adjuvant therapy in breast cancer patients. Sentinel lymph node biopsy (SLNB) represents a minimally invasive procedure with low morbidity for staging axillary nodal status. In this article we review and report our experiences in patients with early breast cancer who underwent SLNB at the Revlon/UCLA Breast Center. Between September 1998 and May 2000, a total 83 SLNBs were performed in 81 patients with proven breast cancer and negative axillary examination who elected to have SLNB as the first step of nodal staging. Two patients had bilateral breast cancer. SLNB was localized by using both 99Tc sulfur colloid (83 cases) and isosulfan blue dye (75 cases). Data of these patients were prospectively collected and analyzed. The clinical and pathologic characteristics of women with positive and negative sentinel lymph nodes (SLNs) were compared to identify features predictive of SLN metastasis. Of the 83 cases, the SLN was successfully localized in 82 (98.8%). Sixty-three percent of patients had SLNs found in level I only, 18.3% in both level I and II, and 4.9% in level II alone. The vast majority (84.3%) of these cases had T1 breast cancer with an average size of 1.55 cm for the entire series. Twenty-three patients (28%) had positive SLNs, with an average of 1.5 positive SLNs per patient. Fifteen had metastases detected by hematoxylin and eosin staining and 8 had micrometastases detected by immunohistochemistry (IHC) using anticytokeratin antibodies. Ten of the former group agreed to and 2 of the latter group opted for full axillary lymph node dissection (ALND). An average of 17.5 lymph nodes were removed from each ALND procedure. Additional metastases or micrometastases were found in seven patients (in a total of 28 lymph nodes). Three patients with completely negative SLNs experienced additional axillary lymph node removal due to their election of free flap reconstruction. None had metastases detected in these lymph nodes. The absence of estrogen and progesterone receptors (ER/PR) by IHC (p = 0.036) and the presence of lymphatic/vascular invasion (LVI) (p = 0.002) predicted positive SLNs in patients with early breast cancer in a univariate analysis; in a multivariate analysis only LVI was predictive (p = 0.0125). Histologic type, nuclear grade, tumor differentiation, HER-2/neu and p53 status, S-phase fraction, and DNA ploidy did not predict SLN status. Immediate postoperative complications were uncommon and delayed complications completely absent. Because of the high detection rate, accurate staging, and minimal morbidity, SLNB should be offered as a choice to women with small breast cancers and clinically negative nodes. Because positive LVI and negative ER/PR status are highly predictive of pathologically positive SLNs in small breast cancers, women whose cancers meet these criteria should be advised preoperatively about their risk of having a positive SLN and may benefit from intraoperative assessment (frozen section and/or touch preparation) of their SLNs.     

Prediction of additional axillary metastasis of breast cancer following sentinel lymph node surgery

Sentinel lymphadenectomy is a sensitive and specific procedure that has reduced the need for complete axillary lymph node dissections in patients with negative sentinel lymph nodes (SLNs). However, numerous studies have shown that SLN may be the only positive lymph node in 40 to 70% of cases. This study was therefore undertaken to determine if the characteristics of primary breast tumor or its metastasis in the SLN could predict the presence of residual disease in the nonsentinel lymph nodes (NSLNs) and thus allow for further reduction in axillary lymph node surgery. The SLN procedure was performed on 329 patients at our institution, of which 131 had positive SLNs and underwent further axillary surgery. Fifty-four patients had additional disease in the NSLNs, while in the remaining 77 cases, no residual disease was detected. The clinical and pathologic features of these cases were reviewed and statistical analysis was performed. Multivariate analysis determined two significant independent variables for prediction of residual disease in the axilla: the size of the metastatic tumor in SLNs and the presence of its extranodal extension. The mean tumor size in SLNs without residual disease in NSLNs was 0.4 cm. It was 1.1 cm in patients with additional NSLN metastasis. The positive predictive value in both instances is about 80%. The risk of NSLN involvement in patients with SLN tumors of < or = 0.4 cm was 21%. The risk was the same (21%) for patients with micrometastatic disease (< or = 0.2 cm) in SLNs. In these cases the residual disease in the NSLNs was also small. SLNs with metastatic deposits larger than 1.0 cm were likely to contain additional metastases in the NSLNs in 81% of cases. This increased to 100% if the primary carcinoma was larger than 5 cm, if it was poorly differentiated, or if it showed HER-2/neu gene amplification. The presence of an extranodal extension of SLN metastasis was an independent predictor of residual axillary disease and was associated with NSLN metastasis in 76% of cases. Primary tumor characteristics did not correlate with the incidence of NSLN metastasis in our series.     

淋巴闪烁显像与乳腺癌前哨淋巴结活检

乳腺癌前哨淋巴结的精确定位是乳腺癌前哨淋巴结活检成功的先决条件之一,明确乳腺淋巴引流途径对乳腺癌前哨淋巴结的准确定位有重要指导意义。术前淋巴闪烁显像可提供个体化的淋巴引流特点,有助于确定前哨淋巴结的位置、数目及是否存在腋窝外前哨淋巴结。现对淋巴闪烁显像在乳腺癌前哨淋巴结活检中的应用现状和存在的问题进行综述。     

乳腺癌前哨淋巴结活检的临床应用研究

目的探讨乳腺癌前哨淋巴结活检术（SLNB）在临床应用中的价值。方法应用亚甲蓝染色法对58例乳腺癌患者先行SLNB,随后行乳腺癌常规外科手术。结果58例患者中前哨淋巴结（SLN）检出率为93．1％,准确率为96．3％。假阴性率为5．71％,假阳性率为0;操作者的学习曲线、患者的年龄、原发肿瘤的部位影响SLN的检出率（P〈0．05）;肿瘤的大小、病理类型不影响SLN的检出率（P〉0．05）。结论乳腺癌SLNB能够准确地预测乳腺癌患者腋窝淋巴结（ALN）的转移情况。     

Experience of sentinel node biopsy alone in early breast cancer without further axillary dissection in patients with negative sentinel node

AIMS: The aims of surgical therapy of breast cancer are loco-regional tumour control and staging. Axillary staging is still considered the single most important prognostic indicator in breast cancer. Surgical removal of axillary nodes remains the standard way to assess their involvement in most centres. The morbidity associated with axillary dissection (AD) is well recognized. In recent years sentinel node biopsy (SNB) has evolved. Multiple studies suggest it has the same accuracy as AD in axillary staging and less morbidity in early breast cancer (EBC). SNB has become the standard of practice in EBC in many parts of the world. In Australia, the preference has been to wait for the results of the Sentinel Node versus Axillary Clearance (SNAC) trial as well as other international trials before accepting SNB as a standard of care. The experience of a single surgeon with SNB alone in EBC without further completion axillary dissection (CAD) in negative sentinel node (SLN) is described in the present paper. METHODS: An audit was done of the senior author's prospective data from the Royal Australasian College of Surgeons database. Other information was added retrospectively from case notes. RESULTS: Between December 2000 and December 2003, 154 EBC cases (153 patients) underwent SNB alone. An average of four SLN was removed. Of these cases, 31.8% had positive SLNs (excluding 2.6% cases that had isolated tumour cells), of these, 93.9% had metastases (39.1% micro- and 60.9% macro-metastases) in axillary-SLN (ASLN) and almost all of these had CAD. ASLNs were the only positive nodes in 73.9%. Extra-ASLN retrieved in 68.8% of 34% demonstrated on lymphoscintigraphy. Of these, 12.1% were positive (6.1% micro- and macro-metastases each), all internal mammary. Mean follow up was 22.1 months. There was one local-regional-systemic and one systemic recurrence over this time. CONCLUSION: SNB has a valid role in staging of the axilla particularly in low-risk patients. After adequate self audit, SNB offers a minimal morbidity and reliable method of axillary staging. Patients choosing SNB alone must understand that the long-term results of the randomized controlled trial are still pending for level I evidence of long-term efficacy.     

前哨淋巴结活检在乳腺癌中的临床应用

目的 探讨术中前哨淋巴结（sentinel lymph node,SLN）定位和活检（SLNB）对预测乳腺癌腋窝淋巴结（axillary lymph node,ALN）转移的准确性.方法 对48例乳腺癌患者术前10min用亚甲蓝注射液4ml注射到肿瘤周围或活检腔的正常乳腺组织,进行SLN定位和活检,然后行乳腺癌改良根治术.结果 SLNB的检出成功率为95.8%,准确率为97.8%,假阴性率3.0%,假阳性率为0.结论 用亚甲蓝作SLN定位进行SLNB能准确预测乳腺癌ALN转移状态.     

Early experience of sentinel lymph node biopsy in breast cancer with blue dye technique

Objective: Sentinel lymph node biopsy (SLNB) is a minimally invasive staging procedure for breast cancer. Results of the first 30 cases of SLNB performed at Kwong Wah Hospital, Hong Kong, were reviewed. Design: This feasibility study applied and assessed a new procedure in Chinese patients. The study was carried out at the Breast Centre, Kwong Wah Hospital, Hong Kong. Sentinel lymph node biopsy was performed with a blue dye technique alone. All patients had full axillary dissection after SLNB. Patients: Female patients with invasive carcinoma of breast and no clinical palpable axillary lymph node were included. Main outcome measures: Pathological results of both the SLN and the remaining axillary content were compared. Results and Conclusion: Sentinel lymph nodes were successfully biopsied in 83% of cases. Sensitivity was 75% and accuracy was 88%. With experience, sentinel lymph node biopsy is feasible in Chinese patients.     

Intraoperative palpation for clinically suspicious axillary sentinel lymph nodes reduces the false-negative rate of sentinel lymph node biopsy in breast cancer

Axillary sentinel lymph node biopsy (SLNB) is widely used to identify the first lymph node draining breast tumors. When the sentinel lymph node is free of metastasis, axillary dissection is avoided because the rest of the nodes are expected to be negative as well. A false-negative rate of 5% is considered acceptable. In the case of a false-negative SLNB, adjuvant local and systemic treatments might be suboptimal. We assessed the effect of intraoperative axillary palpation for clinically suspicious lymph nodes that are not otherwise detected by radioactive tracer or blue dye on the false-negative rate of SLNB in breast cancer patients. Our prospective database of patients having surgery for primary invasive breast cancer and who had a SLNB from 2000 to 2004 was reviewed. Only patients with clinically negative nodes preoperatively were included. The procedure included preoperative injection of radiotracer, with dye injection as backup, and intraoperative palpation of the axilla for suspicious lymph nodes that were not radioactive or blue. Of the 290 patients, 89 (30.7%) had sentinel node involvement by tumor. Seven patients had clinically suspicious nodes identified solely by palpation and not by tracer, in addition to sentinel lymph nodes detected by tracer. In five of the seven patients, the nodes harbored metastasis. In four of these five patients (4.5% of the 89 patients with axillary involvement), the palpable nodes were the only ones involved. A generous axillary incision and systematic palpation of the axilla reduces the false-negative rate and should be a part of the SLNB procedure.     

Failure of sentinel lymph node mapping in breast cancer patients qualified for treatment sparing axillary lymph nodes—Clinical importance and management strategy—One‐center analysis

Sentinel lymph node biopsy (SLNB) is a standard in diagnostic and therapeutic management of patients with nonadvanced invasive breast cancer. The aim of this paper was to evaluate the clinical importance of the failure of sentinel lymph node (SLN) identification during SLNB performed to spare axillary lymph nodes. A total of 5396 patients with invasive breast cancer qualified for SLNB, treated in a period from Jan 2004 to June 2018. All cases of the failure of SLN identification and reasons underlying this situation were analyzed retrospectively. In 196 (3.6%) patients, SLN was not identified (group I), and this resulted in a simultaneous axillary lymph node dissection. 48.5% patients from this group were diagnosed with cancer metastases to lymph nodes (vs 23.6% patients with SLN removed—group II, P < .00001)—stage pN1 in 44.2% of the cases, stage pN2 in 22.1% of the cases, and pN3 in 33.7% (in group II—73.4%, 19.5% and 7.1%, respectively), with a presence of extracapsular infiltration in 68.4% patients (vs 41.7% in group II) and with a significantly higher percentage of micrometastatic nature in group II (17.0%, vs 3.2% in group I). The failure of intraoperative sentinel lymph node mapping indicates a significantly increased risk of breast cancer metastases to the axillary lymph system. At the same time, it can also indicate higher cancer stage and its increased aggressiveness. For this reason, in such situation performance of axillary lymph node dissection still appears to be the approach most advantageous for patients.     

Alternative sites of injection for sentinel lymph node biopsy in breast cancer

Background: Sentinel node biopsy is rapidly gaining popularity as a less invasive approach to nodal staging in breast cancer. The optimal route of injection of radiocolloids and dye is controversial. The purpose of the present paper was to review and assess the literature. Methods: A MEDLINE search for reports of studies involving different injection sites of colloid and/or dye was performed. Results: Although controversial, current evidence suggests that subareolar (SA) or intradermal/subdermal (ID/SD) injection will map the same axillary sentinel nodes (SN) as peritumoral (PT) injection in the vast majority of cases, is at least as successful, and is better logistically. Peritumoral, but not alternative routes, identify extra‐axillary sentinel nodes, which are important in a minority of patients. Conclusions: It is recommended that at least some of the radiocolloid be injected peritumorally to avoid missing those SN not located in the ipsilateral axilla. Injection of the dye and a portion of radiocolloid in an ID/SA location is reasonable to take advantage of the general ease and accuracy of ID/SA injections in identifying axillary SN.     

Preoperative lymphatic mapping does not predict the number of axillary sentinel lymph nodes identified during surgery in breast cancer patients

Sentinel lymph node biopsy (SLNB) has become the standard of care in most centers for axillary staging in patients with early breast cancer. Multiple radioactive nodes are often identified at surgery. The finding of multiple sentinel lymph nodes (SLNs) has been shown to be associated with lower rates of false-negative results in the SLNB procedure, hence the importance of removing and examining all SLNs. Often preoperative lymphatic mapping (PLM) is performed prior to surgery. In this study we examined whether the exact number of SLNs identified during surgery can be accurately predicted by PLM. During the years 2001-2004, 155 patients underwent both PLM and a SLNB in our breast unit. During surgery, an attempt was made to remove all radioactive nodes. The number of axillary radioactive foci found on PLM was compared with the number of radioactive nodes identified during surgery. The average number of sentinel nodes harvested was 2.3 (range 1-9). The average number of radioactive foci identified on PLM was 1.8 (range 0-5). Of the 155 patients, the number of sentinel nodes retrieved in surgery was greater than that found in preoperative mapping in 65 patients (41.9%), equal to that found in preoperative mapping in 60 patients (38.7%), and less than that found in preoperative mapping in 30 patients (19.4%). Thus in most patients, the number of SLNs found on PLM did not reflect the number of SLNs found intraoperatively. Therefore, even when the number of nodes identified on PLM has been reached in surgery, a meticulous search for additional nodes should still be carried out. The number of hot spots in preoperative mapping should serve as a rough indicator of the smallest number of nodes the surgeon should attempt to resect, but not the exact number of nodes expected to be found.     

美蓝染色法检测乳腺癌前哨淋巴结的临床研究

目的 寻找检测乳腺癌前哨淋巴结(SLN)方法，研究前哨淋巴结活检(SLNB)预测腋窝淋巴结状况的准确性。方法 对40例乳腺癌患者行美蓝染色法检测SLN，并行腋窝淋巴结清扫术(ALND)后，将腋窝淋巴结转移状况与SLN进行对比分析，分析SLN检出率及临床特征。结果 40例患者中成功检测出SLN35例，成功率为87．5％。检出SLN60个，平均每例检出SLNl．7个。2例出现假阴性，假阴性率为10.5％，无假阳性。35例患者中有16例SLN阳性，阳性率为45.7％。SLNB预测腋窝淋巴结(ALN)的敏感性为88．8％，特异性为100％，准确性为94．4％。结论 美蓝染色法检测乳腺癌SLN经济实用，可以较准确地预测腋窝淋巴结的转移状况。     

Women's choice between sentinel lymph node biopsy and axillary clearance

Purpose : To determine whether women would choose sentinel lymph node biopsy (SLNB) or axillary clearance (AC) for breast cancer treatment when they are given a single choice based on clear information about morbidity and mortality. Methods : The expected 5‐year survival rate of women with breast cancer after either SLNB or AC was calculated using a utility analysis of established literature. The difference in survival was one in 1000. This and other detailed information on SLNB and AC was presented in a questionnaire, which provided subjects with a scenario and a choice between SLNB and AC. After a pilot study of 40 subjects, the questionnaire was mailed to 400 women (who had no mammographic abnormality) attending Breast Screen and handed to 100 women (who were over 40 years of age and had breast symptoms but not cancer) attending the rooms of two surgical specialists. Results : One hundred and twenty one of the 243 respondents to the mailed questionnaires (49.8%) chose SLNB and 35% of the 100 consulting room subjects chose SLNB rather than AC. Conclusions : Women faced with the possibility of having breast cancer seem to be very conservative in their choice of treatment, many choosing the increased morbidity of AC rather than the very small (one in 1000) increased risk of death at 5 years from SLNB. This raises questions about proposals to offer SLNB as standard treatment and demands that women are fully informed about any increased risk of death when making their choice between SLNB and AC. Abbreviations: AC, axillary clearance; SLNB, sentinel lymph node biopsy.     

Primary tumor characteristics predict sentinel lymph node macrometastasis in breast cancer

Selective sentinel lymphadenectomy (SSL) is rapidly becoming the standard of care in the surgical management of patients with early breast cancer. Sentinel lymph node macrometastasis has been well documented in the literature to have a higher risk of nonsentinel node tumor involvement when compared to micrometastasis. The aim of our study was to determine the primary tumor characteristics associated with sentinel node macrometastasis that will allow us to preoperatively determine this subgroup of patients at risk. This study was a retrospective review of 644 patients who underwent successful SSL as part of their surgical treatment of breast cancer at the University of California San Francisco Carol Franc Buck Breast Care Center from November 1997 to August 2003. All patients underwent preoperative lymphoscintigraphy followed by wide excision or mastectomy and sentinel lymphadenectomy with or without axillary lymph node dissection. One hundred twenty-two patients had positive sentinel nodes on histology. Micrometastasis was present in 43 of these patients and macrometastasis in the remaining 79. Statistical analysis showed that a tumor size greater than 15 mm, poor tubule formation by the tumor cells, and lymphovascular invasion were significantly associated with sentinel node macrometastasis. A high mitotic count showed a trend but was not significant in our study. Patients with a tumor size greater than 15 mm, poor tubule formation, and lymphovascular invasion are at risk of having sentinel node macrometastasis. These patients can be identified preoperatively based on imaging and biopsy criteria, allowing the option of selective intraoperative pathologic evaluation of the sentinel node and immediate completion axillary dissection as necessary.     

乳腺癌的保留乳房手术及哨兵淋巴结活检103例报告

目的 总结乳腺癌保留乳房手术及哨兵淋巴结活检的临床经验。方法 103例乳腺癌患者，肿块局部扩大切除23例，乳腺区段切除加腋淋巴结清扫80例。全部病例均行哨兵淋巴结活检。结果 活检与术后病理对照，准确性95．8％，假阴性率14．1％，假阳性率0。随访10个月至7年，2例4年内复发，7例5年内复发，10例7年内复发。复发者均改行乳腺癌改良根治术。结论 早期乳腺癌中。行保留乳房的乳腺癌手术可行。术后应进行根治性放疗及全身化疗，可获得满意效果。     

Reoperative sentinel lymph node biopsy in patients with locally recurrent breast cancer

BACKGROUND: Sentinel lymph node biopsy (SLNB) is considered a standard of care in the staging of breast cancer. The objective was to examine our experience with reoperative SLNB. METHODS: We identified 19 patients in our breast cancer database who had a SLNB in the reoperative setting. All 19 patients had undergone previous breast-conserving surgery with either an axillary lymph node dissection or an SLNB. The reoperative sentinel lymph node (SLN) was identified using blue dye, radioisotope, or both. RESULTS: The SLN was identified in 84% of the reoperative cases. Of these successful cases, both blue dye and radioisotope were used in five cases, and radioisotope alone was used in 11 cases. Radioisotope identified the SLN in the 100% of successful SLNB cases (P = .0003). There were 3 unsuccessful cases in which blue dye and radioisotope failed to identify the sentinel node. CONCLUSIONS: Reoperative SLNB after previous axillary surgery is technically feasible.     

应用亚甲蓝行乳腺癌前哨淋巴结活检276例分析

目的 探讨以亚甲蓝作为示踪剂行乳腺癌前哨淋巴结(SLN)活检的临床应用及影响因素.方法 分析了276例临床T1-T2 N0-M0乳腺癌患者前哨淋巴结活检(SLNB)结果,对SLN检出率及假阴性率影响因素进行了初步分析.结果 276例患者中,成功检出SLN者246例(检出率为89.1%).共检出SLN 423枚,每例1～4枚.前哨淋巴结对腋窝淋巴结转移情况预测的敏感性为77.3%(68/88),假阴性率为8.1%(20/246),假阳性率为0,准确率为91.9%(226/246).临床T2N0M0SLNB成功率高于临床T1N0M0乳腺癌患者(P=0.046);年龄<50岁者SLNB检出成功率高于年龄≥50岁病例(P=0.000),SLNB假阴性率年龄<50岁者显著低于高龄患者(P=0.037);外上象限和外下象限肿瘤SLNB检出成功率明显高于其他象限(P=0.000).内上象限肿瘤SLNB假阴性率高于外上及外下象限(P=0.018).临床TMN分期、EB、PR表达情况及病理类型对SLNB成功率及假阴性率无影响.结论 以亚甲蓝作为示踪剂行乳腺癌SLNB,患者年龄、临床TNM分期、肿瘤部位对SLN检出率有一定影响,患者年龄、肿瘤部位可影响SLNB假阴性率.     

腋窝淋巴结清扫术治疗前哨淋巴结活检阴性乳腺癌的系统评价

目的系统评价腋窝淋巴结清扫术治疗前哨淋巴结活检阴性乳腺癌的有效性和安全性。方法检索CNKI、PubMed、EMBASE、CBM从建库至2013年12月1日的文献资料,选择腋窝淋巴结清扫术和前哨淋巴结活检术治疗乳腺癌患者的试验,严格按照制订纳入和排除标准对纳入的研究进行筛选、资料提取、质量评价和结果分析。使用Revman 5.1软件,进行统计学分析(Meta-分析)。结果最终纳入10篇文献,患者共7731例。因纳入文献在研究类型、测量指标、随访时间以及统计学指标的差异较大,采用亚组分析,Meta分析同质研究,其余采用定性的描述性分析。本研究结果显示,在无病生存率、总体生存率、局部复发率、远处转移率方面,不同随访时间腋窝淋巴结清扫术与前哨淋巴结切除术间差异均无统计学意义。结论对于单发浸润性乳腺癌患者前哨淋巴结活检呈阴性时,可不必行腋窝淋巴结清扫术。目前尚需相关高质量随机对照试验和长期的随访进一步证实此系统评价的结论。