前哨淋巴结活检在皮肤型和肢端型黑色素瘤临床诊疗中的价值

背景与目的：前哨淋巴结活检（sentinel lymph node biopsy,SLNB）是评估皮肤型和肢端型黑色素瘤区域淋巴结转移情况及病理学分期的重要手段。SLNB作为外科诊疗规范的重要环节,已在各大诊疗指南中被推荐,也已在中国临床应用近10年。自2017年靶向和免疫治疗应用于中国黑色素瘤治疗领域,患者预后得到显著改善。本研究旨在分析复旦大学附属肿瘤医院近5年恶性黑色素瘤患者的临床资料,评估在新药治疗时代前哨淋巴结（sentinel lymph node,SLN）状态在临床应用的价值和对预后的影响。方法：对2017—2021年在复旦大学附属肿瘤医院黑色素瘤诊治中心接受诊治的381例恶性黑色素瘤患者的临床资料进行回顾性分析。每例患者均接受原发灶扩大切除和相应的SLNB,手术后随访至少6个月。SLN定位使用美兰染色或同位素示踪。结果：本研究共入组381例恶性黑色素瘤患者,平均Breslow浸润深度为3.10 mm,69.8%为肢端型,溃疡率为57.1%,SLN阳性率为34.6%,中位无复发生存率（relapse-free survival,RFS）为17个月。SLN状态是显著影响患者预后的独立危险因素。在N_1a和T₄亚组,SLN活检数>2枚的患者具有更好的RFS。接受完整的区域淋巴结清扫（complete lymph node dissection,CLND）和未清扫患者的RFS差异无统计学意义,在SLN活检数>2枚和SLN微转移直径<1 mm的亚组未清扫者反而具有更优的RFS。结论：SLN状态仍是影响临床无显性转移的黑色素瘤预后的重要因素,对于恶性黑色素瘤患者应常规开展SLNB,在保证微创的前提下,提高SLN定位的准确性,保证SLNB充分。SLN阳性后行即刻CLND对于皮肤型和肢端型黑色素瘤患者未能带来进一步的预后改善。     

前哨淋巴结活检对黑色素瘤预后的预测价值

目的探讨前哨淋巴结活检(SLNB)对黑色素瘤预后的预测价值。方法回顾性分析2012年3月至2019年6月北京积水潭医院诊治的118例黑色素瘤患者的临床病理资料。患者术前行体格检查和影像学检查排除区域淋巴结转移,采用99Tcm-右旋糖酐行术前示踪显像,术中γ射线探测仪精准定位,切取前哨淋巴结(SLN)行病理活检;原发灶局部行扩大切除重建术;SLN病理阳性患者行区域淋巴结清扫。采用Cox回归模型分析患者的预后及其影响因素。结果118例患者的病史为2~360个月,平均病史为53.6个月。原发灶位于手足84例,甲下27例,皮肤7例。平均Breslow厚度为3.6 mm,合并溃疡72例(61.0%,72/118)。全组患者平均切取SLN 2.8枚,SLN阳性29例(24.6%,29/118),假阴性率为2.5%(3/118)。淋巴结显性转移和远处转移24例(20.3%,24/118),其中远处转移合并淋巴结转移7例(5.9%,7/118),单纯淋巴结显性转移8例(6.8%,8/118),远处脏器转移9例(7.6%,9/118)。全组患者病理分期为Ⅰ期33例,Ⅱ期56例,Ⅲ期29例,5年生存率为69.5%。Breslow厚度为SLN阳性的独立危险因素,Breslow厚度、SLN状态、SLN阳性数目和远处转移是影响患者总生存的独立影响因素(均P<0.05)。结论对于临床及影像学检查无区域淋巴结转移的患者,SLNB能够提供准确的病理分期并预测患者的预后,临床应常规开展。     

Effects of time interval between primary melanoma excision and sentinel node biopsy on positivity rate and survival

BackgroundSentinel node biopsy (SNB) is essential for adequate melanoma staging. Most melanoma guidelines advocate to perform wide local excision and SNB as soon as possible, causing time pressure.ObjectiveTo investigate the role of time interval between melanoma diagnosis and SNB on sentinel node (SN) positivity and survival.MethodsThis is a retrospective observational study concerning a cohort of melanoma patients from four European Organization for Research and Treatment of Cancer Melanoma Group tertiary referral centres from 1997 to 2013. A total of 4124 melanoma patients underwent SNB. Patients were selected if date of diagnosis and follow-up (FU) information were available, and SNB was performed in <180 d. A total of 3546 patients were included. Multivariable logistic regression and Cox regression analyses were performed to investigate how baseline characteristics and time interval until SNB are related to positivity rate, disease-free survival (DFS) and melanoma-specific survival (MSS).FindingsMedian time interval was 43 d (interquartile range [IQR] 29–60 d), and 705 (19.9%) of 3546 patients had a positive SN. Sentinel node positivity was equal for early surgery (≤43 d) versus late surgery (>43 d): 19.7% versus 20.1% (p = 0.771). Median FU was 50 months (IQR 24–84 months). Sentinel node metastasis (hazard ratio [HR] 3.17, 95% confidence interval [95% CI] 2.53–3.97), ulceration (HR 1.99, 95% CI 1.58–2.51), Breslow thickness (HR 1.06, 95% CI 1.04–1.08), and male gender (HR 1.58, 95% CI 1.26–1.98) (all p < 0.00001) were independently associated with worse MSS and DFS; time interval was not.InterpretationNo effect of time interval between melanoma diagnosis and SNB on 5-year survival or SN positivity rate was found for a time interval of up to 3 months. This information can be used to counsel patients and remove strict time limits from melanoma guidelines.     

PET CT imaging in patients undergoing sentinel node biopsy for melanoma.

AIMS: Sentinel lymph node biopsy (SLNB) has been adopted in the surgical treatment of melanoma to reduce morbidity and enhance staging. Positron emission tomography with computerised tomography (PET/CT) has been utilised in the staging of patients with malignancy though the role of this imaging modality in early stage melanoma is unclear. This study examined the preoperative value of PET/CT in patients undergoing SLNB for malignant melanoma. METHODS: Patients presenting with primary melanoma without evidence of either locoregional or systemic metastasis were considered candidates for SLNB. Selected patients underwent preoperative PET/CT followed by definitive surgical therapy including SLNB with regional lymphadenectomy, where indicated. RESULTS: During a 12-month period 83 patients were identified as having undergone SLNB for melanoma, of which 37 (45%) had preoperative PET/CT. Mean melanoma thickness 1.9 mm and 2.4 mm (PET/CT vs. no PET/CT, p>0.05). 13 (15.6%) patients were found to have lymphatic metastasis at SLNB; nine of these patients underwent PET/CT, only two of these scans were suggestive of lymphatic metastasis (positive predictive value 24%, negative predictive value 76%). PET/CT revealed no unheralded metastatic disease but did identify a second occult malignancy in 4 (10.8%) patients undergoing therapy for melanoma. CONCLUSIONS: The results of this study do not support the use of PET/CT in patients undergoing SLNB for melanoma. SLNB appears to be a more sensitive staging modality in the detection of lymphatic metastasis; however PET/CT may have a future role as a screening tool for malignancy.     

Sentinel node biopsy versus elective lymph node dissection in patients with cutaneous melanoma in a Japanese population

Background In Japan, elective lymph node dissection (ELND) has been the standard treatment for patients with possible nodal melanoma. Sentinel node biopsy (SNB) has now replaced ELND, not only in Japan but also worldwide. The objective of this study was to compare the interim outcomes of SNB and ELND. Methods A retrospective study was conducted among patients with clinically node-negative disease treated at our institute with either SNB (n = 30) or ELND (n = 72). Results The background was similar in the two groups. Nodal metastases were found in 40.0% of patients in the SNB group, but in only 26.4% in the ELND group (P = 0.173). The median follow-up was 31.5 months for the SNB group and 82 months for the ELND group. The incidence of locoregional recurrence and distant metastasis in the SNB group was 10.0% and 16.7%, respectively, and for the ELND group the incidence was 5.6% and 31.9%, respectively. The 3-year disease-free survival rate was similar in the two groups (P = 0.280), and the 3-year disease-free survival rates for node-positive patients were also similar in the two groups (P = 0.90), as were the 3-year disease-free survival rates for node-negative patients (P = 0.193). Conclusion This interim result in a Japanese melanoma population with clinically node-negative disease demonstrated that SNB identified more nodal micrometastases than ELND. This increase in accurate staging likely resulted from the reliable identification of the lymph node field by lymphoscintigraphy, as well as the more detailed pathologic examination of the nodes removed in SNB. It is quite reasonable to perform SNB instead of ELND in this population.     

Contemporary controversies and perspectives in the staging and treatment of patients with lymph node metastasis from melanoma,especially with regards positive sentinel lymph node biopsy

The management of melanoma lymph node metastasis particularly when detected by sentinel lymph node biopsy (SLNB) is still controversial. Results of the only randomized trial conducted to assess the therapeutic value of SLNB, the Multicenter Selective Lymphadenectomy Trial (MSLT-1), have not conclusively proven the effectiveness of this procedure but are interpreted by the authors and guidelines as indicating SLNB is standard of care. After surgery, interferon alpha had a small survival benefit and radiotherapy has limited effectiveness for patient at high-risk of regional recurrence. New drugs, including immune modulating agents and targeted therapies, already shown to be effective in patients with distant metastasis, are being evaluated in the adjuvant setting. In this regard, ensuring high quality of surgery through the identification of reliable quality assurance indicators and improving the homogeneity of prognostic stratification of patients entered onto clinical trials is paramount. Here, we review the controversial issues regarding the staging and treatment of melanoma patients with lymph node metastasis, present a summary of important and potentially practice changing ongoing research and provide a commentary on what it all means at this point in time.     

Assessment of a new scoring system for predicting non-sentinel node positivity in sentinel node-positive melanoma patients

Background

When completion lymph node dissection (CLND) is performed in sentinel node (SN)-positive melanoma patients, a positive non-sentinel node (NSN) is found in approximately 20% of them. Recently, Murali et al. proposed a new scoring system (non-sentinel node risk score, N-SNORE) to predict the risk of NSN positivity in SN-positive patients. The objectives of the current study were to identify factors predicting NSN positivity and to assess the validity of the N-SNORE in an independent patient cohort.

Methods

All SN-positive patients who underwent CLND at a single institution between 1995 and 2010 were analyzed. Characteristics of the patient, primary melanoma, and SN(s) were tested for association with NSN positivity. Missing values were reconstructed using multiple imputation to enable multivariable analysis.

Results

CLND revealed positive NSNs in 30 (23%) of 130 SN-positive patients. Primary melanoma regression (p = 0.03) was independently associated with NSN positivity. After adjustment because of missing data on perinodal lymphatic invasion, N-SNORE proved to be a significant stratification model in our patient cohort (p = 0.003): 5.9% NSN positivity in the very low risk category and 75.0% NSN positivity in the very high risk category.

Conclusions

Presence of regression in the primary melanoma was independently associated with a higher risk of NSN positivity. The slightly modified N-SNORE scoring system provided useful stratification of the risk for NSN positivity. However, lack of perinodal lymphatic invasion data may have reduced its predictive value.     

The prognostic role of the sentinel lymph node in clinically node-negative patients with cutaneous melanoma: experience of the Genoa group

AIM: To define the benefit of intraoperative frozen section examination of the sentinel lymph node (sN), and to assess its prognostic value in clinically node-negative melanoma patients. MATERIALS AND METHODS: Between July 1993 and December 2001, 214 patients with Stage I-II cutaneous melanoma underwent sN biopsy; complete follow-up data are available in 169 of 175 patients who underwent preoperative lymphoscintigraphy, lymphatic mapping with Patent Blue-V and radio-guided surgery (RGS). RESULTS: In an initial subset, the sN was identified in 35 out of 39 patients; in the principal group of 169 patients, the sN was detected in all patients. The benefit of frozen section examination, that is the proportion of all patients having intraoperative histologic examination who tested positive, was 17.2% (29/169); notably, in patients with pT(1-2) vs pT(3-4) melanoma the corresponding values were 2.3 and 33.3%, respectively, (P=0.000). Cox regression analysis for overall survival indicated that sN-positive patients had a two-fold increased risk of death; the most significant predictors of relapse-free survival were sN status (P=0.004), age (P=0.015), and T stage grouping (P=0.033). CONCLUSIONS: The sN is a reliable predictor of regional lymph node status in patients with cutaneous melanoma. Frozen section examination can be useful in avoiding a 'two-stage' operative procedure in patients with tumour-positive sN, but its greatest benefit seems to be restricted to patients with pT(3)-pT(4) primary melanoma.     

Prognostic heterogeneity after the excision of lymph node metastases in patients with cutaneous melanoma

Background

The aim of this study was to compare the overall survival (OS) of different groups of AJCC 2002 stage III cutaneous melanoma patients and to prove that patients with positive sentinel lymph node (SN) are heterogenic group with very different survival rates.

Methods

A total of 325 patients with stage III melanoma were identified from the prospective melanoma database at the Institute of Oncology Ljubljana, Slovenia; 164 had delayed therapeutic lymph node dissection (DLND), 111 had a positive sentinel lymph node biopsy followed by completion lymph node dissection (CLND) and 50 had synchronous primary melanoma and regional lymph node metastases that were treated with radical excision of the primary tumor and therapeutic lymph node dissection (TLND). Univariate and multivariate analyses were used for the assessment of the factors associated with OS and for comparison of OS between different subgroups of patients.

Results

The worst 5-year OS had the patients with synchronous primary melanoma and regional lymph node metastases. The patients with SN metastases with a diameter of 5.0 mm or less had significantly better OS than those with DLND, while the patients with SN metastases with a diameter of more than 5.0 mm had similar survival to those patients with synchronous primary melanoma and regional lymph node metastases.

Conclusion

Melanoma patients within AJCC 2002 stage III group have very different survival rates. The group of patients with positive SN is also prognostically heterogenic because it contains patients that have better survival than those after DLND as well as patients with more aggressive disease, that have similar survival as those with synchronous primary melanoma and regional lymph node metastases.     

The use of indocyanine green and near-infrared fluorescence imaging to assist sentinel lymph node biopsy in cutaneous melanoma: A systematic review

Background and objectivesDespite the use of blue dye and radioisotopes, sentinel lymph node biopsy (SLNB) is still associated with a high false-negative rate (FNR). The off-label use of indocyanine green (ICG) and near-infrared fluorescence (NIRF) imaging has been introduced with the objective of assisting SLNB and thereby improving regional control in melanoma. The objective of this study was to review and summarize the general experience, protocols and outcomes of the use of ICG and NIRF to assist SLNB in melanoma.MethodsA systematic literature review was performed in December 2019 as per the PRISMA guidelines. Inclusion criteria were articles written in English describing the applications of ICG in patients with melanoma. Systematic reviews, animal studies, case reports and letters to editors were excluded.ResultsOf the 585 studies retrieved, 13 articles met the inclusion criteria. The reported sentinel lymph node (SLN) detection rate using ICG was between 86 and 100% of nodes identified by lymphoscintigraphy. The average number of nodes per patient detected using ICG was 2. ICG fluorescence imaging contributed to the identification of 2.0% of the total number of SLNs harvested.ConclusionsICG fluorescence may be a useful adjunct to lymphoscintigraphy, although high-level comparative data is lacking. It was found to be superior to blue dye at detecting sentinel lymph nodes.     

皮肤恶性黑素瘤的前哨淋巴结活检技术

目的:评估前哨淋巴结活检(sentinel lymph node biopsy,SLNB)应用于皮肤恶性黑素瘤诊断和治疗中的临床价值。方法:对18例临床评估无区域淋巴结转移的皮肤恶性黑素瘤患者,应用淋巴核素显像以及术中核素扫描等方法定位前哨淋巴结(sentinel lymph node,SLN);切除SLN后进行快速冰冻和常规石蜡切片病理检查,若SLN为阳性,则加行相应区域淋巴结清扫。结果:18例患者中共检出SLN34枚,其中阳性7枚(20.6%)。5例SLN阳性患者加行区域淋巴结清扫,包括3例腹股沟清扫、1例腋窝清扫和1例颈部清扫;除SLN以外,共清扫淋巴结84枚,其中阳性39枚(46.4%)。结论:SLNB有助于诊断皮肤恶性黑素瘤的淋巴转移,为实施区域淋巴清扫提供重要的临床依据。     

Prediction of non-sentinel node status and outcome in sentinel node-positive melanoma patients

Aims: Sentinel lymph node (SLN) -positive melanoma patients are usually recommended completion lymph node dissection (CLND) with the aim to provide regional disease control and improve survival. Nevertheless, only 20% these patients have additional metastases in non-sentinel lymph nodes (NSLN), indicating that CLND may be unnecessary in the majority of patients. In this retrospective study, we (i) sought to identify clinico-pathological features predicting NSLN status, as well as disease-free (DFS) and -specific (DSS) survival and (ii) evaluated the applicability of previously published algorithms, which were able to define a group of patients at zero-risk for NSLN-metastasis.     

乳腺癌前哨淋巴结活检的可行性及临床应用价值

目的 探讨前哨淋巴结(sentinel Iymph node,SLN)定位和活检(SLNB)的可行性及其对预测乳腺癌腋窝淋巴结(axillary lymph node,ALN)转移的准确性。方法 对52例临床查体及B超检测ALN阴性的乳腺癌患者,术中在肿瘤周围注射亚甲蓝进行SLN定位和活检。对常规病理检查阴性的SLN再行免疫组化检测。结果 SLNB的检出成功率为92.3％(48/52),准确率为97.9％,假阴性率为4.8％,敏感度为95.2％,特异度为100％。SLN是惟一被证实有肿瘤转移的淋巴结者占66.7％(14/21)。免疫组化检测使SLN肿瘤转移的阳性率提高了4.1％。结论乳腺癌SLNB技术是可行的,应用亚甲蓝淋巴定位方法进行的SLNB可以准确预测临床及B超检查ALN阴性的乳腺癌患者的ALN转     

前哨淋巴结活检指导保留乳房手术患者行选择性腋窝淋巴结清除术的研究

目的研究通过前哨淋巴通道（SLC）行前哨淋巴结活检（SLNB）以指导保留乳房手术（breast—conservingtherapy,BCT）患者行选择性腋窝淋巴结清除术（ALND）的可行性。方法采用非随机对照研究,在BCT患者中采用联合示踪法通过SLC行SLNB。对术中检出的前哨淋巴结（SLN）行细胞印片和冰冻切片检查,根据SLN的术中病理结果行选择性ALND,其中SI。N阳性、行ALND者为A组,SI。N阴性仅行SLNB者为B组。定性资料的比较选用Y。检验,两组均数的比较采用t检验。结果2009年1月至2009年12月采用联合示踪法行SLNB的BCT患者共43例,检出42例,A组28例,B组14例。两组患者的SLC均被显影。每例患者被检出SLN1～3枚,平均1．4枚,共被检出59枚。SLNB检出率为97．7％（42／43）。术后病理检查共检出阳性SI,N29例,其中术中细胞印片、冰冻切片及二者联合病理检测分别检出阳性淋巴结27、27、28例。A组ALND相关并发症发生率明显高于B组（P=0．003）。结论通过SLC行SLNB有助于准确定位SLN,能够指导BCT患者行选择性ALND,降低术后并发症。     

Long-term follow-up reveals that ulceration and sentinel lymph node status are the strongest predictors for survival in patients with primary cutaneous melanoma

Purpose

To assess the long-term outcome after sentinel lymph node biopsy (SLNB) in melanoma patients.

Methods

Between 1995-2009 450 melanoma patients underwent SLNB in a single center. Survival and prognostic factors were analyzed for 429 patients.

Results

Median age was 53 (range 11-84) years. Median Breslow thickness was 2.4 (range 1-20) mm and 36% were ulcerated melanomas. Median follow-up time was 64.8 (range 2-174) months. A tumor-positive SLN was present in 140 patients (31%). Completion lymph node dissection (CLND) was performed in 119 patients and these patients were analyzed for recurrence and survival.124 Patients (29%) relapsed during follow-up; 55 in the node-positive group who underwent CLND (55/119; 46%) and 69 in the node-negative group (69/310; 22%; p < 0.001). In the node-negative group 17 patients developed recurrence in the regional node field; false-negative rate 11%.On multivariate analysis strongest prognostic factors for disease free survival (DFS) were primary melanoma ulceration and SLN positivity (Hazard Ratio (HR) of 2.2 and 2.3; p < 0.001). For disease specific survival (DSS) the same was found to be true with an HR of 2.1 for ulceration and 2.0 for SLN positivity (p = 0.001 and p = 0.002 respectively). 10-Year DFS was 71% for node-negative patients compared with 48% for node-positive patients (p < 0.001). 10-Year DSS was 77% for node-negative patients compared to 60% for node-positive patients (p < 0.001).

Conclusions

This study shows a remarkably high percentage of tumor-positive SLN. The long-term follow-up data confirm that tumor-positive SLN patients have a worse DFS and DSS than tumor-negative SLN patients. Ulceration and SLN status proved to be the strongest prognostic factors for long-term DFS and DSS.     

Ultrasound-guided fine needle aspiration cytology as an addendum to sentinel lymph node biopsy can perfect the staging strategy in melanoma patients

BackgroundUltrasound guided fine needle aspiration cytology (US-guided FNAC) can identify microscopic involvement of lymph nodes as in breast cancer and avoid surgical sentinel node (SN). Its utility in melanoma patients is controversial and subject of this study.MethodsBetween 2001 and 2010 over 1000 stage I/II consecutive melanoma patients prospectively underwent US-FNAC prior to SN biopsy. All patients underwent lymphoscintigraphy prior to US-FNAC. The Berlin US morphology criteria: Peripheral perfusion (PP), loss of central echoes (LCE) and balloon shaped (BS) were registered. FNAC was performed in case of presence of any of these factors. SN tumour burden was measured according to the Rotterdam criteria. All patients underwent SN or lymph node dissection (LND) in case of positive FNAC.FindingsMean/median Breslow thickness was 2.58/1.57 mm. Mean/median follow-up was 56/53 months (1–132). SN positivity rate was 21%. US-FNAC Sensitivity was 71% (US only) and 51% (US-FNAC). Sensitivity of US-FNAC was highest for T4 (76%) and ulcerated melanomas (63%). PP, LCE and BS had sensitivity of 69%, 24% and 24% respectively. Sensitivity of US-FNAC increased with increasing SN tumour burden. PP was an early sign of metastasis (58% in <0.1 mm metastases). Threshold size of a metastasis for FNAC was 0.3 mm. Five-year survival correlated to US-FNAC status (95% in negative and 59% in positive).InterpretationUltrasound guided FNAC (US-FNAC) according to the Berlin morphology criteria could correctly identify at least half of all tumour positive sentinel nodes, prior to the surgical SN procedure. Peripheral perfusion is an early sign of metastasis, which is very sensitive, but with lower positive predictive value (PPV). It is responsible for the sensitivity of the procedure. Balloon shape is a sign of advanced metastases, with lower sensitivity, but high PPV. US-FNAC sensitivity correlated with increasing T-stage, ulceration of the primary and increasing SN tumour burden. US-FNAC status accurately predicts survival.     

Maximizing the clinical usefulness of a nomogram to select patients candidate to sentinel node biopsy for cutaneous melanoma

Aims

Investigators from the Memorial Sloan Kettering Cancer Centre (MSKCC) have proposed a nomogram for predicting the sentinel node (SN) status in patients with cutaneous melanoma. The negative predictive value (NPV) of this test, which might help identify low-risk patients who might be safely spared SN biopsy (SNB), has not been yet investigated.

Methods

We tested the discrimination (area under the curve [AUC]), the calibration (linear regression) and the NPV of MSKCC nomogram in 543 patients treated at our institution. Different cut-off values were tested to assess the NPV, the reduction of SNB performed and the overall error rate obtained with the MSKCC nomogram.

Results

SN was positive in 147 patients (27%). Mean predicted probability was 17.8% (95%CI: 16.8-18.8%). Nomogram discrimination was significant (area under the curve = 0.68; P < 0.0001) and mean predicted probabilities of SN positivity well correlated with the observed risk (R² = 0.99). Cut-off values between 4% and 9% led to a NPV, SNB reduction and overall error rates ranging between 100 and 91.2%, 2.2 and 27.2%, and 0 and 2.3%, respectively.

Conclusion

In our series, the nomogram showed a significant predictive accuracy, although the incidence of SN metastasis was higher than that observed in the MSKCC series (27% vs 16%). Using the nomogram, a NPV greater than 90% could be obtained, which would be associated with a clinically meaningful reduction of the SNB rate and an acceptable error rate. If validated in large prospective series, this tool might be implemented in the clinical setting for SNB patient selection.     

Axillary recurrence after negative sentinel lymph node biopsy

Background Sentinel lymph node biopsy (SLNB) has almost totally replaced axillary lymph node dissection as the first-line axillary procedure for node-negative breast cancer. SLNB has a false-negative rate of 0–22%, and regional nodal recurrence is a major concern after SLNB. In this study, we assessed axillary recurrence and risk factors in breast cancer patients 40 months after negative SLNB. Methods Of 940 patients with node-negative breast cancer who underwent SLNB between December 2003 and January 2006 at Asan Medical Center, 720 were negative on SLNB, as determined using 99-m TC radiocolloid and subareolar injection technique. Of the 720 patients negative on SLNB, 174 underwent further axillary dissection, 253 underwent node sampling, and 293 received SLNB only. Results A mean of 2.1 SLNs was removed per patient. At a median follow-up of 40 months (range 24–49 months), recurrence in the axilla was observed in three patients, all of whom had undergone SLNB only; two of these patients also had recurrences in internal mammary lymph nodes. Tumors in all three patients were hormone-receptor negative, and two were c-erbb2 negative. Conclusion The axillary recurrence rate was low in patients negative on SLNB. Negative hormone-receptor status and high nuclear grade may be risk factors for regional nodal failure after SLNB.