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。     

Factors influencing sentinel lymph node identification failure in breast cancer surgery

The purpose of this study was to investigate potential risk factors for failed sentinel lymph node identification in breast cancer surgery. Patient characteristics, tumour characteristics, surgeon experience and detection success/failure were registered at 748 sentinel lymph node biopsy procedures at our inpatient clinic. Data were analysed with backward stepwise multiple logistic regression with a cut-off point of p<0.05. We found that increased age, increased BMI, medial tumour location and less surgeon experience independently were associated with a lower sentinel lymph node detection rate. Tumour size, palpability and biopsy method were not significantly associated with the sentinel lymph node detection rate. In conclusion, it is possible to identify patients with a higher risk of sentinel lymph node identification failure and we recommend that these patients are operated by experienced surgeons in order to avoid accumulation of independent risk factors in individual cases.     

乳腺癌前哨淋巴结活检存在的几个问题

前哨淋巴结活检（SLNB）在乳腺外科已被广泛应用，但仍有一些问题存在争议，如示踪剂的选择、示踪剂注射的最佳部位、如何评价淋巴闪烁显像、腋窝外前哨淋巴结（SLN）特别是内乳SLN的意义、SLN微转移的检测及其意义、SLNB对导管原位癌患者的意义、新辅助化疗对SLNB的影响以及腋窝淋巴结清扫的价值等问题。笔者对乳腺癌SLNB的现状和当前存在的问题进行综述，希望有助于规范该技术并促进其病例选择的一致性。     

Recommendations for sentinel lymph node processing in breast cancer

The status of the sentinel lymph node (SLN) has been shown to accurately reflect the presence or absence of metastases in the axilla in patients with breast cancer. This study was designed to determine the optimal protocol for SLN processing. A total of 173 SLNs from 96 breast cancer patients who had successful SLN localization and underwent completion axillary node dissection were identified. All SLNs were negative for metastases by initial routine histologic evaluation. The nodes were submitted in a total of 300 blocks. Each block was serially sectioned to produce 10 levels. Pan-cytokeratin stain was performed on levels 3 and 8. All other levels were stained with hematoxylin and eosin. Metastases were identified in 22 SLNs from 19 patients by examining all 10 levels. The first two hematoxylin and eosin- or the first cytokeratin-stained levels were positive for metastases in 21 (95.5%) of the 22 positive SLNs. Two additional hematoxylin and eosin-stained and one cytokeratin-stained levels of each SLN correctly identified the status of the node in 94 (97.9%) of 96 patients. Therefore, we recommend that after an initial hematoxylin and eosin-stained section, two additional hematoxylin and eosin-stained sections and one cytokeratin-stained section should be evaluated.     

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。     

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。     

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.     

Radiation therapy as an adjuvant treatment after sentinel lymph node surgery for breast cancer

Radiation therapy is an effective treatment of micrometastatic disease involving lymph nodes. Correspondingly, radiation may be an important adjuvant treatment for selected patients who undergo sentinel lymph node surgery. The specific cohorts for whom radiation maybe of benefit include those at risk for a false-negative surgery, patients with a positive sentinel lymph node who elect to forgo an axillary dissection, and patients with drainage to the internal mammary lymph nodes. For these patients, radiation treatment fields must be specifically designed to include the appropriate nodal regions within the target treatment volumes.     

Evaluation of sentinel lymph node biopsy after previous breast surgery for breast cancer: GATA study

AimSentinel lymph node (SLN) biopsy was recently recommended after prior breast tumour surgery and lymphadenectomy is not the gold standard anymore for nodal staging after a lesion's removal. The purpose of our study was to evaluate the good practices of use of SLN biopsy in this context.Patients and methodsFrom 2006 to 2012, 138 patients having undergone a surgical biopsy without prior diagnosis of an invasive carcinoma with a definitive histological analysis in favour of this diagnosis were included in a prospective observational multicentric study. Each patient had a nodal staging following SLN biopsy with subsequent systematic lymphadenectomy.ResultsThe detection rate of SLN was 85.5%. The average number of SLNs found was 1.9. The relative detection failure risk rate was multiplied by 4 in the event of an interval of less than 36 days between the SLN biopsy and the previous breast surgery, and by 9 in the event of using a single-tracer detection method. The false negative rate was 6.25%. The prevalence of metastatic axillary node involvement was 11.6%. In 69% of cases only the SLN was metastatic. The post-operative seroma rate was 19.5%.ConclusionPrevious conservative breast tumour surgery does not affect the accuracy of the SLN biopsy. A sufficient interval of greater than 36 days between the two operations could allow to improve the SLN detection rate, although further studies are needed to validate this statement.Clinical trial registration numberNCT00293865.     

Technical advances in sentinel lymph node biopsy for breast cancer

Technical advances in the past several years have simplified and improved sentinel lymph node (SLN) biopsy for breast cancer. The use of alternative injection sites (skin or subareolar) yields high SLN identification rates and may shorten the learning curve associated with standard peri-tumoral injection. The dual-agent (radiocolloid plus blue dye) technique is now recommended to decrease false-negative rates, especially when surgeons are just learning how to perform SLN biopsy. Methylene blue may be an acceptable substitute for isosulfan blue dye and is associated with fewer hypersensitivity reactions. Hand-held gamma probes are now smaller and more maneuverable, with better shielding for directional detection of gamma rays. Routine preoperative lymphoscintigraphy can be avoided, thus facilitating operating room scheduling. Surgeons can use minimally invasive techniques to identify and remove internal mammary SLNs.     

Current controversies in sentinel lymph node biopsy for breast cancer

Despite the widespread use of sentinel lymph node biopsy (SLNBx) in the surgical management of breast cancer patients, several areas remain controversial. The following controversies are reviewed: Learning curves and validation studies. There clearly is a learning curve, and a completion ALND should be done until adequate proficiency is exhibited, both in terms of identification and false-negative rates. Location of injection. Intradermal injection offers superior identification rates compared with peritumoral injection, with comparable false-negative rates. Subareolar injection is as accurate as peritumoral injection. The value of scintigraphy. Routine scintigraphy does not enhance identification or false-negative rates. Mapping agents. Blue dye and radioactive tracer combined to provide a higher identification rate than either used alone.SLNBx in DCIS. In patients with a high risk of microinvasion, such as large tumors, a mass or high-grade DCIS-SLNBx is justified.SLNBx following neoadjuvant chemotherapy. Although there is evidence that SLNBx after neoadjuvant chemotherapy may be accurate, these data should be applied cautiously. Implications of non axillary SLN, especially internal mammary nodes. Data do not support routine resection of internal mammary sentinel lymph nodes outside a clinical trial.Implications of micrometastases in the sentinel lymph node seen only on immunohistochemistry. Since the significance of such metastases is unclear, decisions regarding treatment of these patients should be individualized. The value of completion axillary lymph node dissection. Is being addressed in clinical trials. Until those studies mature, completion ALND should be performed for patients with SLN metastases, but may be abandoned for patients with a negative SLN.     

Axillary recurrence after sentinel lymph node biopsy for breast cancer

Sentinel lymph node biopsy (SLNB) is routinely performed as an axillary staging procedure for breast cancer. Although the reported false-negative rate approaches 10 per cent, this does not always lead to axillary recurrence. We previously reported an axillary recurrence rate of 1 per cent at a median follow-up of 2 years. Our objective is to determine the rate of axillary recurrence with longer follow-up. A retrospective review of patients with invasive breast cancer and a negative SLNB treated between 2001 and 2005 was performed. Cases where neoadjuvant therapy was used or where isolated tumor cells (ITCs) were found were included, whereas those with fewer than 18 months of follow-up were excluded. One (0.7%) out of 139 patients had an axillary recurrence after a median follow-up of 52 months. No patient who underwent neoadjuvant chemotherapy or with ITCs had axillary recurrence. Twelve (8.6%) patients have died, with death attributed to breast cancer in three. Our study demonstrates that axillary recurrence after SLNB remains a rare event after a median follow-up of 52 months, despite including potentially higher risk scenarios such as where neoadjuvant chemotherapy is used and ITCs are found. Therefore, axillary lymph node dissection can safely be avoided in patients where SLNB is negative.     

Credentialing issues with sentinel lymph node staging for breast cancer

Sentinel lymphadenectomy (SL) is a minimally invasive approach for staging patients with breast cancer. SL, when performed in lieu of axillary dissection, is associated with less morbidity and is potentially more cost effective and more accurate than the historical axillary dissection in the detection of regional nodal metastases. The credentialing and privileging of SL, as with any surgical procedure, is by the policies of the local hospital or institution. The suggested credentialing criteria for local hospitals has been an area of controversy. Herein the authors outline the credentialing controversy and suggest criteria for the implementation of sentinel lymph node staging for breast cancer.     

Pre-operative lymphoscintigraphy before sentinel lymph node biopsy for breast cancer

Pre-operative lymphoscintigram for axillary sentinel lymph node biopsy (SLNB) may not be required for successful SLNB. The 117 consecutive patients who underwent SLNB had pre-operative lymphoscintigraphy. The operating surgeon was blinded to the results of the lymphoscintigram before SLNB. After SLNB was complete, the surgeon was unblinded to the results of the lymphoscintigram; re-exploration carried out if more nodes were predicted on the lymphoscintigram. 116 patients (99%) had successful SLNB before unblinding. In 85 patients (73%), operative findings corresponded with scintigraphic findings. In 26 patients (22%), the lymphoscintigram predicted more sentinel nodes than had been found; further nodes were identified and excised in only 4 patients (3%). None were positive for cancer. SLNB was successful in 99% of cases without pre-operative lymphoscintigraphy. Only 3% of patients had further nodes identified as a result of the lymphoscintigram. Pre-operative lymphoscintigraphy does not improve the ability to perform axillary SLNB during breast cancer surgery.     

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.