Intradermal radioisotope injection optimises sentinel lymph node identification in breast cancer

AIM: Currently there is no consensus on the optimal technique for sentinel lymph node (SLN) identification in patients with breast cancer. The aim was to compare the efficacy of intraparenchymal and intradermal isotope injection in sentinel lymph node mapping for breast cancer. METHODS: One hundred and twenty-five patients with histologically confirmed invasive breast cancer underwent SLN mapping using radioisotope and isosulphan blue dye followed by a back-up axillary dissection. The first 80 patients had intraparenchymal (IP) injection of radioisotope given in four portions around the tumor. The remaining 45 patients had an intradermal (ID) injection given at a single site over the tumour. Both groups had isosulphan blue dye injected around the tumour. Sentinel node(s) were identified using a combination of lymphoscintigraphy, blue dye and an intra-operative hand held gamma probe. RESULTS: The preoperative lymphoscintigram (LSG) demonstrated a SLN significantly more often in the ID isotope group compared to the IP isotope group (P=0.002). A combination of blue dye and isotope successfully located the SLN in 96% of the intraparenchymal group and 100% of the intradermal group. CONCLUSION: Our results suggest that intradermal isotope injection in combination with intraparenchymal blue dye optimises the localization of the sentinel lymph node in breast cancer.     

Intradermal radioisotope injection is superior to subdermal injection for the identification of the sentinel node in breast cancer patients

BACKGROUND AND OBJECTIVES: The purpose of the present study was to evaluate whether the intradermal injection of radiocolloids would improve the identification rate of sentinel nodes over the subdermal injection in breast cancer patients. METHODS: Sentinel node biopsy was performed in T2 breast cancer patients with clinically negative nodes, using subdermal or intradermal injection of radioisotopes with the peritumoral dye injection. We used Tc-99m tin colloid, with a larger particle size (0.4-5 microm), rather than sulfur colloid and colloidal albumin. RESULTS: The initial 55 patients underwent subdermal injection of radiocolloids; the next 61 patients underwent intradermal injection of radiocolloids for sentinel node biopsy. The detection rate of sentinel nodes was significantly (P = 0.048) higher in the intradermal injection group (61/61, 100%) than in the subdermal injection group (51/55, 92.7%). False-negative rates were comparable between the two groups. Lymphoscintigraphy visualized the sentinel nodes significantly (P < 0.0001) more often in the intradermal injection group (59/61, 96.7%) than in the subdermal injection group (20/54, 37.0%). CONCLUSIONS: A significantly higher identification rate of sentinel node biopsy and lymphoscintigraphy can be achieved by intradermal injection of Tc-99m tin colloid with a large particle size than by subdermal injection.     

Prognosis of breast cancer patients treated with sentinel node biopsy in Japan

BACKGROUND: Sentinel node biopsy predicts accurate pathological nodal staging. The survival of node-negative breast cancer patients should be evaluated between the patients treated with sentinel node biopsy alone and those treated with axillary lymph node dissection. METHODS: Ninety-seven patients with negative axillary nodes underwent sentinel node biopsy immediately followed by axillary lymph node dissection between January 1998 and June 1999 (the ALND group). Since then, if sentinel lymph nodes were negative on the frozen-section diagnosis, 112 patients underwent sentinel node biopsy alone without axillary lymph node dissection between July 1999 and December 2000 (the SNB group). We retrospectively observed the outcome of the two study groups. RESULTS: Median follow-up was 52 months in all patients. Relapse-free survival rates at 3 years in the ALND and SNB groups were 94% and 93%, respectively. Five of the 112 patients in the SNB group had overt axillary metastases. Three of them with axillary metastases alone were treated with delayed axillary lymph node dissection. These three patients have been free of other events for 3 years after local salvage treatment. CONCLUSIONS: Sentinel node biopsy will emerge as a standard method to diagnose axillary nodal staging for clinically node-negative breast cancer patients.     

乳腺癌前哨淋巴结活检的安全性

循证医学Ⅰ、Ⅱ级证据支持乳腺癌前哨淋巴结活检（SLNB）的安全性。本文就SLNB对腋窝淋巴结的准确分期、前哨淋巴结阴性患者SLNB替代腋清扫术后腋窝复发率和并发症、SLNB的放射安全性、SLNB新的适应症进行讨论。     

临床腋窝淋巴结阳性乳腺癌患者内乳区前哨淋巴结活检术研究*

目的：评估临床腋窝淋巴结阳性乳腺癌患者行内乳区前哨淋巴结活检术（IM-SLNB）的临床意义。方法：2013年6 月至2014年10月对山东省肿瘤医院乳腺病中心就诊的64例临床腋窝淋巴结阳性的原发性乳腺癌患者行前瞻性单臂入组研究,采取腋窝淋巴结清扫术,同时均应用新的核素注射技术进行IM-SLNB。结果：64例患者中内乳区前哨淋巴结（IM-SLN）显像为38例,显像率为59.4%（38/ 64）。 38例IM-SLN 显像患者中IM-SLNB 成功率为100%（38/ 38）,并发症发生率为7.9%（3/ 38）,IM-SLN 转移率为21.1%（8/ 38）。 肿瘤位于内上象限和腋窝淋巴结转移数目较多的患者,其IM-SLN 转移率较高（P < 0.001 和P = 0.017）。 患者临床获益率为59.4%（38/ 64）,其中12.5%（8/ 64）另接受了内乳区放疗、46.9%（30/ 64）避免了不必要的内乳区放疗。结论：临床腋窝淋巴结阳性的乳腺癌应进行IM-SLNB,尤其对于肿瘤位于内上象限及怀疑存在较多腋窝淋巴结转移数目的患者,以获得内乳区淋巴结的转移状态,指导乳腺癌患者内乳区放疗。     

Factors influencing the identification rate of the sentinel node in breast cancer

Sentinel node biopsy is a widely accepted alternative to primary axillary lymph node dissection for ipsilateral nodal assessment in breast cancer. We have performed a retrospective chart review in 713 consecutive patients with primary, operable breast cancer who underwent sentinel node biopsy in order to identify factors that determine the sentinel node identification rate. Chi-squared test, univariate and multivariate analyses were used to evaluate the influence of different factors on the sentinel identification rate. Among the factors investigated, tumour size was correlated with sentinel lymph nodes detection rates (multiple logistic regression, P= 0.002). In addition, the patient's age showed to be a significant influencing factor (multiple logistic regression, P= 0.006). Body mass index and grade only exhibited a significant correlation with the identification rate in the univariate (P= 0.041, P= 0.025), but not in the multivariate analysis (P= not significant). All associations were found to be independent of the site of injection. Interestingly, surgeons with intermediate expertise (11-20 prior dissections) had the highest detection rates (P= 0.004). We conclude that sentinel identification rates are higher in larger tumours and in younger patients, independent of the injection site. Surgical experience in sentinel node dissection is not linearly correlated with higher identification rates.     

亚甲蓝在乳腺癌前哨淋巴结活检中的应用

目的探讨亚甲蓝作为蓝染料在乳腺癌前哨淋巴结活检中的应用价值。方法对已确诊的72例乳腺癌病人亚甲蓝皮下注射后行腋窝前哨淋巴结切除,送冰冻病理检查,再行乳腺癌改良根治术,并常规腋窝淋巴结清扫,术后病理石腊切片检查前哨淋巴结及手术切除标本。结果本组病例中68例共检出前哨淋巴结132枚,失败4例。前哨淋巴结的检出率94.4%,准确率91.8%,敏感度92%,假阴性率8%,假阳性率为0。结论采用亚甲蓝作为蓝染料应用于乳腺癌前哨淋巴结活检术,其前哨淋巴结活检的各项指标与其他蓝染料(专利蓝)相当,且材料广泛、费用低廉,具有临床应用前景。     

乳腺癌前哨淋巴结活检研究进展

近年来,乳腺癌的发病率越来越高,乳腺癌治疗方式也在不断改进,但手术仍然是早期乳腺癌治疗的主要手段。对于早期乳腺癌,前哨淋巴结活检术（sentinel lymph node biopsy,SLNB）是一种安全、精确的手术方式,已逐渐替代腋窝淋巴结清扫术（axillary lymph node dissection,ALND）成为早期乳腺癌治疗的标准术式。随着研究的深入,SLNB的应用范围更广,术后生活质量显著改善,但其操作尚需要进一步统一规范。在前哨淋巴结微转移、宏转移、前哨淋巴结活检阳性的老年患者以及新辅助化疗的前哨淋巴结活检等方面尚未达成共识,还需要更多大型多中心前瞻性的随机试验来进一步论证。     

High risk of non-sentinel node metastases in a group of breast cancer patients with micrometastases in the sentinel node

Axillary lymph node dissection (ALND) in breast cancer patients with positive sentinel nodes is under debate. We aimed to establish two models to predict non-sentinel node (NSN) metastases in patients with micrometastases or isolated tumor cells (ITC) in sentinel nodes, to guide the decision for ALND. A total of 1,577 breast cancer patients with micrometastases and 304 with ITC in sentinel nodes, treated by sentinel lymph node dissection and ALND in 2002-2008 were identified in the Danish Breast Cancer Cooperative Group database. Risk of NSN metastases was calculated according to clinicopathological variables in a logistic regression analysis. We identified tumor size, proportion of positive sentinel nodes, lymphovascular invasion, hormone receptor status and location of tumor in upper lateral quadrant of the breast as risk factors for NSN metastases in patients with micrometastases. A model based on these risk factors identified 5% of patients with a risk of NSN metastases on nearly 40%. The model was however unable to identify a subgroup of patients with a very low risk of NSN metastases. Among patients with ITC, we identified tumor size, age and proportion of positive sentinel nodes as risk factors. A model based on these risk factors identified 32% of patients with risk of NSN metastases on only 2%. Omission of ALND would be acceptable in this group of patients. In contrast, ALND may still be beneficial in the subgroup of patients with micrometastases and a high risk of NSN metastases.     

Follow-up of sentinel node negative breast cancer patients without axillary lymph node dissection.

BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the feasibility of sentinel lymph node biopsy in breast cancer patients at our institution and to report the follow-up status of node-negative patients with removal of only the sentinel node. METHODS: A total of 247 breast cancer patients underwent sentinel node (SN) mapping between June of 1996 and September of 2000. The SN was identified by using a combination of vital blue dye and a radiolabeled colloid. RESULTS: A SN was identified in 227 of 247 patients (91.9%). One hundred forty-five were SN negative, 82 were SN positive. All SN-positive patients underwent axillary dissection of level I and II, whereas 83 patients with a negative SN had SN biopsy only. Median follow-up of these patients at 22 months revealed no axillary recurrence; the morbidity resulting from SN biopsy was negligible. CONCLUSIONS: Although the follow-up is very short, SN biopsy only in node-negative breast cancer patients had no negative impact on the axillary failure rate and resulted in negligible morbidity.     

Impact of sentinel node biopsy on long-term quality of life in breast cancer patients

Background:

The aim of this study was to assess long-term quality of life (QoL) over a period of 6 years in women with breast cancer (BC) who underwent sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), or SLNB followed by ALND.

Methods:

The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-C30 and the EORTC-QLQ-BR-23 questionnaires were used to assess QoL before surgery, just after surgery, 6, 12 and 72 months later. The longitudinal effect of surgical modalities on QoL was assessed with a mixed model analysis of variance for repeated measurements.

Results:

Five hundred and eighteen BC patients were initially included. The median follow-up was 6 years. During the follow-up, 61 patients died. None of the patients of the SLNB group developed lymphedema during follow-up and the relapse rate was similar in the different groups (P=0.62). Before surgery, global health status (P=0.52) and arm symptoms (BRAS) (P=0.99) QoL scores were similar whatever the surgical procedure. The BRAS score (P=0.0001) was better in the SLNB group 72 months after surgery. Moreover, during follow-up, patients treated with SLNB had lower arm symptoms scores than ALND patients and there was no difference for arm symptoms between patients treated with ALND and those treated with SLNB followed by complementary ALND.

Conclusion:

Long-term follow-up showed that SLNB was associated with less morbidity than ALND.     

The sensitivity of axillary staging when using sentinel node biopsy in breast cancer

AIMS: We aimed to study factors, which enhance the sensitivity of sentinel node biopsy. METHODS: Three hundred and sixty-three clinically node negative breast cancer patients with successful sentinel node biopsy were studied. All focally radioactive and/or blue nodes in the axilla were harvested. All palpably suspicious lymph nodes were also removed for a similar histological evaluation. RESULTS: Sentinel node metastases were found in 129 patients. The metastasis was detected in the three first retrieved sentinel nodes in 126 cases and in the fourth or fifth node in three cases. The 'hottest' sentinel node was not the involved one in 18 cases. Five patients with tumour negative sentinel nodes had metastases in other palpably suspicious nodes. CONCLUSIONS: Harvesting all focally radioactive and/or blue nodes and other palpably suspicious nodes minimises the false negative rate in sentinel node biopsy. Removal of more than five nodes does not significantly improve the sensitivity of axillary staging.     

Morbidity of breast cancer patients following complete axillary dissection or sentinel node biopsy only: a comparative evaluation

Introduction The usefulness of routine axillary dissection (AD) at levels I–II in breast cancer patients has been questioned for years because of the high postoperative morbidity in the shoulder and arm region, and the increasing number of patients with negative nodes. Sentinel node biopsy (SNB) was hoped both to reduce morbidity and to improve the reliability of staging. This study was designed to provide more evidence in this matter by comparing the follow-up data of patients with AD and those with SNB only. Method One hundred forty patients who had undergone AD between 1993 and 1996 were questioned for their subjective and objective symptoms using a questionnaire and subsequently subjected to a clinical examination. Their data were compared with those of 57 patients who had undergone SNB only between 1998 and 2000. Results Local recurrences have not been seen to date. The difference between the two groups in terms of a loss of quality of life was negligible. The differences in overall complaints, number of symptoms, pain, limited range of motion of the operated upper extremity, numbness, paresthesias, and arm swelling as well as perceived disability in activities of daily living were significantly in favor of SNB. The length of hospital stay was significantly shorter for SNB patients. Conclusion SNB appears to be an accurate procedure for axillary nodal staging in breast cancer patients and is associated with reduced postoperative morbidity and length of hospital stay. But it is still investigational and should not be implemented as therapeutical standard before results of randomized trials are published.     

前哨淋巴结活检术在早期乳腺癌保乳术中的应用

目的探讨前哨淋巴结活检术（sentinellymph node biopsy,SLNB）在早期乳腺癌保乳术中的应用效果。方法回顾性分析56例pT1.2N0M0期乳腺癌行保乳术＋前哨淋巴结活检术的临床资料。56例SLN阴性,未行腋窝淋巴结清扫术（axillary lymph node dissection,ALND）。术后辅以化疗、放疗,激素受体阳性患者行内分泌治疗。结果56例成功施行保乳手术,保乳术后双乳对称。SLNB替代ALND者各项术后并发症少。中位随访时间36个月（1～72个月）,1例发现局部复发,行乳腺癌改良根治术时发现腋窝淋巴结转移;1例发现腋窝淋巴结复发转移。结论SLNB可以缩小手术范围,减少术后并发症,保留腋窝形态,提高保乳质量。     

Lymphoscintigraphic and intraoperative detection of the sentinel lymph node in breast cancer patients: the nuclear medicine perspective

The concept of sentinel lymph node biopsy in breast cancer surgery relates to the fact that the tumor drains in a logical way via the lymphatic system, from the first to upper levels. Therefore, (1) the first lymph node met (the sentinel node) will most likely be the first one affected by metastasis, and (2) a negative sentinel node makes it highly unlikely that other nodes are affected. Sentinel lymph node biopsy would represent a significant advantage as a mini-invasive procedure, considering that, after operation, about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Although the pattern of lymphatic drainage from a breast cancer can be very variable, the mammary gland and the overlying skin can be considered as a biologic unit in which lymphatics tend to follow the vasculature. Considering that tumor lymphatics are disorganized and relatively ineffective, subdermal, and peritumoral injection of small aliquots of radiotracer is preferred to intratumoral administration. (99m)Tc-labeled colloids with most of the particles in the 100-200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy, as images are used to direct the surgeon to the site of the node. The sentinel lymph node should have a significantly higher count than background. After removal of the sentinel node, the axilla must be re-examined to ensure all radioactive sites are identified and removed for analysis. The success rate of radioguidance in localizing the sentinel lymph node in breast cancer surgery is about 94-97% in Institutions where a high number of procedures are performed, approaching 99% when combined with the vital blue dye technique. At present, there is no definite evidence that a negative sentinel lymph node biopsy is invariably correlated with a negative axillary status, except perhaps for T(1a-b) breast cancers, with size < or =1 cm. Randomized clinical trials should elucidate the impact of avoiding axillary node dissection in patients with a negative sentinel lymph node on the long-term clinical outcome of patients.     

乳腺癌前哨淋巴结活检的研究进展

前哨淋巴结活检（SLNB）是本世纪继早期乳腺癌保乳治疗后第二个最重要的进展,前哨淋巴结活检是种多学科结合的新方法,比腋窝淋巴结清扫更能准确的进行腋窝分期,乳腺癌前哨淋巴结活检很快运用到临床实践。适当选择病人,由有经验的多学科团队进行前哨淋巴结活检,其精确度超过95％,前哨淋巴结活检广泛应用在可触及的和不可触及的T1和T2的肿瘤病人。最近研究表明,前哨淋巴结活检技术可应用在多中心多病灶的和新辅助化疗后和局部晚期乳腺癌病人。前哨淋巴结活检的重要因素包括注射技术,病例选择,病理分析和活检精确度等,为此简要综述如下。