The benefits and limitations of sentinel lymph node biopsy

Opinion statement The status of the axilla is the single most important prognostic indicator of overall survival in patients with breast cancer. Staging is based on tumor size and on the presence of lymph node metastases. The number of lymph nodes, although prognostic, no longer impacts treatment options. Sentinel lymph node (SLN) mapping and dissection is a more sensitive and accurate technique for nodal evaluation and has been applied to staging of axillary lymph nodes in patients with breast cancer, providing prognostic information, with less surgical morbidity than with axillary lymph node dissection (ALND). When analyzed by an experienced pathologist with serial sectioning and immunohistochemical evaluation, SLN is the most accurate detection tool used in staging of breast cancer. In many centers that use these staging principles, ALND is no longer performed for histologically negative axillary SLNs. In addition, this technique may also be therapeutic because in most patients, the SLN is the only positive axillary node. SLN biopsy is justified in women with ductal carcinoma in situ who have a high risk of invasive carcinoma, such as those with large tumors, a mass, or high-grade lesions. SLN biopsy is performed in the setting of neoadjuvant chemotherapy and demonstrates accurate evaluation of the axilla in 90% of the cases. Women with locally advanced breast cancer may derive great benefit from a minimally invasive approach to the axilla because the extent of nodal involvement is unlikely to change further treatment. For clinically palpable nodes, ALND should be performed for therapeutic and local control. The use of sentinel node mapping in pregnancy is controversial. Vital blue dye is contraindicated in pregnant patients, although some have used radioactive colloid alone to map this subgroup of patients.     

Sentinel lymph node biopsy in male patients with early breast cancer

Mastectomy with axillary dissection is still the most commonly recommended procedure for male breast cancer. The aim of this study was to retrospectively evaluate our experience in 32 male patients with early breast cancer who underwent sentinel lymph node biopsy (SLNB) and axillary dissection only in cases of metastases in the sentinel lymph node (SLN). The median age was 58 years (range, 33-80). Lymphoscintigraphy was successful in all patients, with a mean number of visualized SLNs per patient of 1.3 (range, 1-2). At surgery, the identification rate of the SLN was 100%, with a mean number of removed SLNs per patient of 1.5 (range, 1-3). Twenty-six patients had negative SLNs, six patients had positive SLNs. Two patients with metastatic SLNs had additional positive nodes. After a median follow-up of 30 months (range, 1-63) no axillary reappearance of the disease occurred. As with women, we recommend SLNB in male patients with breast cancer and clinically negative axilla.     

Sentinel lymph node mapping in breast cancer

Sentinel lymph node (SLN) biopsy is a rapidly emerging treatment option for patients with early-stage invasive breast cancer and a clinically negative axilla. In the era of mammographic detection, SLN biopsy has the potential to eliminate axillary dissection for the enlarging cohort of breast cancer patients who are node-negative. Using radioisotope, blue dye, or both methods, experienced surgeons can successfully localize SLNs in more than 90% of cases. The effects of isotope and blue dye may be additive. Sentinel lymph node biopsy reliably predicts axillary node status in 98% of all patients and 95% of those who are node-positive. The operation is best learned under a formalized protocol in which a backup axillary dissection is performed to validate the technique during the surgeon's early experience. Enhanced pathologic analysis, including serial sections and immunohistochemical (IHC) staining, is an essential element of the procedure. In experienced hands, SLN biopsy has less morbidity and greater accuracy than conventional axillary dissection.     

Feasibility and accuracy of sentinel lymph node biopsy after preoperative chemotherapy in breast cancer patients with documented axillary metastases

BACKGROUND: The feasibility and accuracy of sentinel lymph node (SLN) biopsy in patients with breast cancer after preoperative chemotherapy has been demonstrated in a number of large, single-institution studies. However, a relative contraindication to SLN biopsy after preoperative chemotherapy is the presence of axillary metastases at initial diagnosis. The objective of this study was to determine the feasibility and accuracy of SLN biopsy after preoperative chemotherapy in patients with documented axillary metastases at presentation. METHODS: Between 1994 and 2002, 69 patients who had axillary metastases identified by ultrasound-guided, fine-needle aspiration underwent SLN biopsy after treatment on prospective, preoperative chemotherapy protocols. All but 8 patients underwent axillary lymph node dissection (ALND). Those 8 patients either declined additional surgery or were offered enrollment in other institutional protocols. RESULTS: The median patient age was 49 years, and the median primary tumor size was 4 cm. The SLN identification rate was 92.8%. Thirty-one of 64 patients (48.4%) had successfully mapped, positive SLNs. Sixty-one patients underwent ALND, including 5 patients who did not have an SLN identified. In the 56 patients in whom a SLN was identified and an ALND was performed, 10 patients had a false-negative SLN (25%). CONCLUSIONS: SLN biopsy was feasible after preoperative chemotherapy, even in patients who initially presented with cytologically proven, lymph node-positive disease. However, the false-negative rate of SLN biopsy in this group of patients was much higher than that observed in clinically lymph node-negative patients. Based on the current results, the status of the SLN cannot be used as a reliable indicator of the presence or absence of residual disease in the axilla in this patient population.     

Sentinel lymph node mapping in breast cancer

Sentinel lymph node (SLN) biopsy is a rapidly emerging treatment option for the patient with early stage invasive breast cancer and a clinically negative axilla. In the era of mammographic detection, SLN biopsy has the potential to eliminate axillary dissection for the enlarging cohort of breast cancer patients who are node-negative. With experience, using radioisotope, blue dye, or both, SLN are successfully localized in more than 90% of cases. The effects of isotope and blue dye may be additive. The SLN reliably predicts axillary node status in 98% of all patients, and 95% of those who are node-positive. The operation is best learned under a formalized protocol in which a backup axillary dissection is performed to validate the technique during one's early experience. Enhanced pathologic analysis, including serial sections and immunohistochemical staining, is an essential element of the procedure. In experienced hands, SLN biopsy has less morbidity and greater accuracy than conventional axillary dissection.     

Elderly breast cancer patients treated by conservative surgery alone plus adjuvant tamoxifen: fifteen-year results of a prospective study

BACKGROUND: In elderly patients with early breast cancer and a clinically clear axilla, axillary surgery, sentinel lymph node biopsy, and postoperative radiotherapy to the residual breast may not be necessary because of reduced life expectancy, effectiveness of hormone therapy in achieving long-term disease control, and generally favorable biologic behavior of breast cancer in elderly patients. METHODS: The authors followed 354 prospectively recruited women aged > or =70 years who had primary, operable breast cancer and no palpable axillary lymph nodes. All 354 women were treated with conservative surgery and adjuvant tamoxifen and without axillary dissection or postoperative radiotherapy. Women who had resection margins in tumor tissue were excluded. Endpoints were cumulative incidence of axillary disease, cumulative incidence of ipsilateral breast tumor recurrence (IBTR), and breast cancer mortality. RESULTS: After a median follow-up of 15 years (interquartile range, 14-17 years), the crude cumulative incidence was 4.2% (4% in pathologic T1 [pT1] tumors) for axillary disease, 8.3% (7.3% in pT1 tumors) for IBTR, and 17% for breast cancer mortality. Of the 268 patients who died during follow-up, 222 patients (83%) died from causes unrelated to breast cancer. CONCLUSIONS: Elderly patients with early breast cancer and no palpable axillary lymph nodes may be safely treated safety by conservative surgery without axillary dissection and without postoperative radiotherapy, provided that surgical margins are in tumor-free tissue and that hormone therapy is administered. Sentinel lymph node biopsy is also unnecessary because of the low cumulative incidence of axillary disease, and axillary surgery can be reserved for the small proportion of patients who later develop overt axillary disease.     

核素淋巴显像识别前哨淋巴结在乳腺癌治疗中的应用

目的评价核素淋巴显像和γ探针定位在乳腺癌中确定前哨淋巴结(SLN)的应用价值,验证前哨淋巴结活检替代腋窝淋巴结清除术用于乳腺癌治疗的安全性与价值。方法选择1999年6月至2009年11月本院住院的女性乳腺癌患者206例(体检时腋窝均未扪及肿块),应用99Tcm-DX37～74 MBq或99Tcm-SC74 MBq经皮下注射,行核素淋巴显像后,术中注射专利兰1 ml和(或)术中用γ探针定位并行前哨淋巴结活检,与术中冰冻病理检查结果对照。若术中冰冻发现有前哨淋巴结转移,则行腋窝淋巴结清除术,若前哨淋巴结阴性,则不做腋窝淋巴结清除,术后定期随访。结果 206例乳腺癌术中成功活检SLN204例,成功率为99.0%(204/206)。本组有64例仅行SLN切除,术后病理检查证实64例SLN均阴性,故未行腋窝淋巴结清除,其中仅1例于术后1年时出现腋窝淋巴结转移,其余63例患者在随访期间均未发现腋窝淋巴结转移,也未出现同侧上肢水肿、感觉及活动异常;另140例行腋窝淋巴结清除,其中6例经病理证实SLN阳性但腋窝淋巴结为阴性,134例经病理证实SLN阳性35例,阴性99例,腋窝淋巴结阳性37例,阴性97例。核素淋巴显像和γ探针定位法的灵敏度为94.6%(35/37例),准确率为98.5%(138/140),假阴性为5.4%(2/37)。结论核素淋巴显像和γ探针定位应用于乳腺癌是切实可行和可能的,对预测腋窝淋巴结转移有很大的临床实用价值。如技术方法规范,早期乳腺癌前哨淋巴结活检则能取代常规的腋窝淋巴结清除术,乳腺癌手术上肢并发症的发生率可大大降低。     

Sentinel lymph node biopsy is feasible for breast cancer patients after neoadjuvant chemotherapy

BACKGROUND: Despite the increasing use of both sentinel lymph node (SLN) biopsy and neoadjuvant chemotherapy (NAC) in patients with operable breast cancer, information on the feasibility and accuracy of sentinel node biopsy following neoadjuvant chemotherapy is still quite limited. Therefore, we investigated the feasibility and accuracy of sentinel lymph node biopsy for breast cancer patients after NAC. METHODS: A total of 104 patients with Stage II and III breast cancers, previously treated by NAC, were enrolled in the study. All patients were clinically node-negative after NAC. The patients underwent SLN biopsy, which involved a combination of an intradermal injection of radiocolloid and a subareolar injection of blue dye over the tumor. This was followed by completion axillary lymph node dissection (ALND). RESULTS: SLN could be identified in 97 of 104 patients (identification rate, 93.3%). In 93 of the 97 patients (95.9%), the SLN accurately predicted the axillary status. Four patients' SLN biopsies were false negative, resulting in a false-negative rate of 10.0%. The SLN identification rate tended to be lower among patients with T4 primary tumors prior to NAC (62.5%). CONCLUSION: The SLN identification and false-negative rates were similar to rates in non-neoadjuvant studies. The SLN accurately predicted metastatic disease in the axilla of patients with tumor response following NAC.     

Cigarette smoking and breast cancer risk: update of a prospective cohort study

SummaryIntroduction Ultrasound (US) preoperative examination of the axillary lymph nodes combined with the fine needle aspiration biopsy (FNAB) is often used in order to reduce the number of sentinel lymph node (SLN) biopsy procedures in clinically node negative breast cancer patients. The pathohistological characteristics of the ultrasonically negative axillary lymph nodes in clinically negative axillary lymph nodes are not known. The aim of our study was to compare the pathohistological characteristics of ultrasonically uninvolved axillary lymph nodes (US group) versus clinically uninvolved axillary lymph nodes (non-US group) in SLN biopsy candidates.Methods We included 658 patients after SLN biopsy; 286 patients in the US group and 372 in the non-US group. The pathohistological characteristics of axillary lymph nodes were evaluated by univariate analysis and logistic regression.Results In the univariate analysis, the proportion of macrometastastic SLN, total number of metastatic lymph nodes per patient, proportion of nonsentinel lymph node (NSLN) metastases and proportion of NSLN macrometastases were found to be lower in the US group compared to the non-US group. In the logistic regression model, only US of the axilla (p=0.010; OR: 0.57) and tumor size were significant predictors for the presence of SLN macrometastases or macrometastatic NSLN (p<0.001; OR: 0.23).Conclusion The patients with US negative axillary lymph nodes form a distinct subgroup of early breast cancer patients having a significantly lower tumor burden in the axillary lymph nodes compared to those with only clinically negative axillary lymph nodes.     

Sentinel lymph node--why study it: implications of the B-32 study

Surgical removal of the regional lymph nodes by a level I and level II axillary dissection remains the standard of care for patients with surgically resectable breast cancer. Axillary dissection provides accurate pathologic staging and excellent regional disease control, and likely provides a small benefit in patient survival. Axillary dissection, however, is associated with significant patient morbidity. Sentinel lymph node (SLN) biopsy procedures have been found to provide very accurate pathologic staging when compared to axillary dissection; however, their effect on regional disease control and patient survival is not yet known. The National Cancer Institute (NCI) has sponsored a Phase III prospective, randomized clinical trial (the B-32 trial) through the National Adjuvant Breast and Bowel Project (NSABP), to compare results of patients treated with SLN biopsy alone vs. SLN biopsy with completion axillary node dissection in patients with clinically node-negative breast cancer. Results of this trial will provide evidence of the safety of SLN biopsy procedures in the management of patients with breast cancer.     

Axillary surgery in breast cancer patients

Surgeons have routinely removed ipsilateral axillary lymph nodes from women with breast cancer for over 100 years. The procedure provides important staging information, enhances regional control of the malignancy and may improve survival. As screening of breast cancer has increased, the mean size of newly diagnosed primary invasive breast cancers has steadily decreased and so has the number of women with lymph node metastases. Recognising that the therapeutic benefit of removing normal nodes may be low, alternatives to the routine level I/II axillary lymph node dissection have been sought. A decade ago sentinel lymph node biopsy (SLNB) was introduced. Because of its high accuracy and relatively low morbidity, this technique is now widely used to identify women with histologically involved nodes prior to the formal axillary node dissection. Specifically, SLNB has allowed surgeons to avoid a formal axillary lymph node biopsy in women with histologically uninvolved sentinel nodes, while identifying women with involved sentinel nodes who derive the most benefit from a completion axillary node dissection. Despite the increasing use of SLNB for initial management of the axilla in women with breast cancer, important questions remain regarding patient selection criteria and optimal surgical methods for performing the biopsy. This article discusses the evolution of axillary node surgery for women with breast cancer.     

Management of the axilla in early breast cancer patients in the genomic era

Management of the axilla in early breast cancer (EBC) patients has dramatically evolved in recent years from more radical to increasingly conservative approaches. Classically, the EBC patients with a clinically positive axilla are offered axillary lymph node dissection (ALND) and those with a clinically negative axilla (cN0) are offered sentinel lymph node (SLN) biopsy, which obviates the complications related to ALND and provides adequate surgical staging and comparable locoregional control and survival. The need for performing ALND when the SLN is positive and contemporary adjuvant treatment is delivered has been questioned in recent years. On the other hand, ongoing trials are testing whether node-positive patients can be spared chemotherapy, based on intrinsic primary tumor biology. Because the integration of novel surgical management and tumor biology is needed, this article provides an overview of the current challenges that a more detailed knowledge of tumor biology has brought to EBC staging and treatment. We propose that breast cancer oncologists (surgeons, radiation therapists, and medical oncologists) should focus their efforts on offering therapy tailored to each patient's needs in such a way that no matter which treatment is used, no overtreatment occurs.     

Sentinel lymph node biopsy in breast cancer after neoadjuvant chemotherapy. A pilot study.

AIMS: Sentinel lymph node biopsy (SLN) seems to represent a reliable method for early breast cancer staging, offering an alternative to complete axillary dissection. METHODS: The identification of sentinel node(s), their localization and the predictive capacity of SLN were analysed in 42 patients who had neoadjuvant chemotherapy for breast cancer. Dextran labelled with (99m)Tc was injected close to the tumor. The radioactive uptake in the axilla was detected by scintigraphic images and by a hand-held probe guided the SLN. RESULTS: One or more sentinel nodes were identified in 41 patients (97.6%). We could accurately predict axillary lymph nodes status in 93% of the cases. CONCLUSIONS: SLN can predict the status of the axilla in patients who have received primary chemotherapy.     

Is There Still a Role for Axillary Dissection in Breast Cancer Surgery?

The operative management of breast cancer has followed a natural progression toward less invasive techniques over the past century as chemotherapy, hormonal therapy, and radiation therapy have become more effective and used more frequently. Sentinel lymph node (SLN) biopsy in clinically node-negative patients has replaced axillary lymph node dissection (ALND), resulting in improved staging and decreased morbidity. ALND has remained important for patients with clinically involved lymph nodes or positive SLN; however, new evidence from the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial has identified a subset of patients with breast cancer who do not benefit from axillary lymphadenectomy following a positive SLN biopsy. These results are practice changing and need to be analyzed within the context of patient selection and multidisciplinary treatment. Herein, we review the emerging data regarding the benefits and indications for axillary lymphadenectomy in the modern era of multidisciplinary breast cancer management.     

New concepts in axillary management of breast cancer

In the last decades, surgical treatment of breast cancer has evolved from more extensive procedures like radical mastectomy to less invasive breast conserving surgery. Similarly, surgical management of axilla has enormously changed from routine axillary dissection to sentinel lymph node biopsy. Traditional surgical approach to the axilla in case of sentinel lymph node negativity is to avoid completion axillary dissection. However, surgeons even avoid performing axillary dissection in selected patients with positive sentinel lymph node in clinical practice depending on the recent randomized controlled studies supporting this concept. All of the recent changes in the management of positive axilla necessitate surgeons to refresh their knowledge on this challenging topic.     

Techniques of sentinel lymph node biopsy

Axillary node status is the single most important prognostic factor for patients with primary breast carcinoma. During the last decade, one of the major advances in breast cancer has been the development of techniques that make axillary staging less morbid and more conservative. The sentinel lymph node (SLN) biopsy technique has received much attention as a possible alternative to axillary lymph node dissection (ALND). The SLN is defined as the first node in the regional lymphatic basin that receives drainage of the primary tumor. We will review the different techniques of lymphatic mapping for breast carcinoma, including radioactive and/or blue dye indicators, timing and site of injection, and preoperative lymphoscintigraphy. The SLN technique involves a multidisciplinary team. It is therefore important that each surgeon validate the technique in his or her own institution to ensure the successful and accurate assessment of the axilla. The SLN technique has modified the surgical management of breast cancer patients, although questions as to its safety have yet to be answered.     

A prospective validation study of sentinel lymph node biopsy in multicentric breast cancer: SMMaC trial

Background

Multicentric breast cancer is often considered a contra-indication for sentinel lymph node (SLN) biopsy due to concerns with sensitivity and false negative rate. To assess SLN feasibility and accuracy in multicentric breast cancer, the multi-institutional SMMaC trial was conducted.

Methods

In this study 30 patients with multicentric breast cancer and a clinically negative axilla were prospectively included. Periareolar injection of radioisotope and blue dye was administered. In all patients SLN biopsy was validated by back-up completion axillary lymph node dissection.

Results

the SLN was successfully identified in 30 of 30 patients (identification rate 100%). The incidence of axillary metastases was 66.7% (20/30). The false negative rate was 0% (0/20) and the sensitivity was 100% (20/20). The negative predictive value was 100% (10/10).

Conclusion

SLN biopsy in multicentric breast cancer seems feasible and accurate and should therefore be considered in patients with multicentric breast cancer and clinically negative axilla.     

Clinical and pathologic factors predicting axillary lymph node involvement in breast cancer

The diagnosis of axillary disease remains a challenge in the management of breast cancer and is a subject of controversy. In 1998, the Japanese Breast Cancer Society conducted a study assessing axillary lymph node involvement in breast cancer. The study included (a) clinical assessment by pre-operative imaging modalities, (b) histologic assessment for peritumoral lymphatic invasion, (c) biologic assessment by gelatinolytic activity using film in situ zymography, and (d) sentinel lymph node (SLN) biopsy. Clinical assessments by CT, PET, and US as well as biologic assessment were limited in their ability to detect axillary lymph node disease, although these imaging techniques may be useful to exclude node-positive patients from the need for SLN biopsy. Histologic assessment for peritumoral lymphatic invasion was useful, particularly for detecting false-negative cases by SLN biopsy. Nevertheless, the utility of SLN biopsy in assessing axillary nodal status was confirmed. Axillary lymph node dissection (ALND) can be avoided in patients with a small tumor and a negative SLN. However, further studies will be required to investigate the value of SLN biopsy for predicting regional control and survival before it can replace routine ALND as the optimal staging procedure for operable breast cancer.     

Sentinel lymph node biopsy following previous axillary surgery in recurrent breast cancer

IntroductionIpsilateral breast recurrence or second primary breast cancer can develop in patients who have undergone breast conserving surgery (BCS) and axillary surgery. The purpose of this study was to examine the feasibility of a reoperative sentinel lymph node biopsy (SLNB) as a repeated axillary staging procedure.Patients and methodsFrom August 2014 through January 2017 patients with locally recurrent breast cancer or with BRCA mutation requiring risk reduction mastectomy as a second surgical procedure, underwent repeat SLNB in three Hungarian Breast Units with a radiocolloid (and blue dye) technique.ResultsHundred and sixty repeat SLNBs were analysed, 80 after previous SLNB and 80 after previous total or partial axillary lymph node dissection (ALND). SLN identification was successful in 106 patients (66%); 77/80 (77.5%) and 44/80 (55%) in the SLNB and ALND groups, respectively. (p < 0.003). Extra-axillary lymph drainage was more frequent in the ALND group (19/44, 43,2% versus 7/62, 11,3%; p < 0.001). Lymphatic drainage to the contralateral axilla was observed in 14 patients (11 in the ALND group, p = 0.025), isolated parasternal drainage was detected in 4 patients (p = 0.31). Only 9/106 patients with successful repeat SLNB (8,8%, all with 1 SLN removed) had SLN metastasesConclusionsRepeat SLNB is feasible in patients with ipsilateral breast tumor recurrence or new ipsilateral primary tumor after previous BCS and axillary staging. Repeat SLNB should replace routine ALND as the standard axillary restaging procedure in recurrent disease with a clinically negative axilla. Preoperative lymphoscintigraphy is important to explore extra-axillary lymphatic drainage in this restaging setting.     

Sentinel lymph node biopsy in multicentric breast cancer. The experience of the European Institute of Oncology.

AIM: To present our experience with sentinel lymph node biopsy (SLNB) performed in patients with multicentric breast cancer. METHODS: Between May 2001 and May 2004, 42 patients with multicentric breast cancer and a clinically negative axilla underwent lymphatic mapping either by a single subareolar (n = 25) or a double peritumoral/subdermal injection (n = 17) of 99Tc-HSA nanocolloids. The sentinel lymph node (SLN) was evaluated by intraoperative frozen section and axillary dissection was performed only in case of positive SLN. RESULTS: Mean age was 49 years (range 25-78). Mean number of SLNs identified by lymphoscintigraphy was 1.36 (range 1-5) and mean number of SLNs removed at surgery was 1.55 (range 1-5), with an identification rate of 100%. The mean number of hot spots identified by lymphoscintigraphy was similar in patients who underwent single or double injections (1.36 and 1.35, respectively). In 21 of 42 patients the SLN was positive, and in seven of these 21 patients the SLN was the only positive node. After a median follow-up of 24 months no overt axillary metastases occurred in patients with negative SLN. CONCLUSIONS: The number of SLNs is not dependent on the number and site of injections. SLNB is our standard procedure for nodal staging in patients with multicentric breast cancer and a clinically negative axilla.