The role of preoperative axillary ultrasound and fine-needle aspiration cytology in identifying patients with extensive axillary lymph node involvement

Introduction

In the recent past, both clinically node-positive and node-negative but sentinel node-positive patients underwent axillary lymph node dissection (ALND), although the two groups seem to have substantially different degree of nodal involvement.

Preoperative predictors of high and low axillary nodal burden in Z0011 eligible breast cancer patients with a positive lymph node needle biopsy result

Background

Z0011 trial showed that early breast cancer patients with low axillary nodal burden, may be spared an axillary lymph node dissection with no survival compromise. Axillary lymph node dissection can be reserved for patients with a high axillary nodal burden. We aim to determine the preoperative factors that could distinguish between low and high axillary nodal burden in Z0011 eligible patients with a needle biopsy proven metastatic node.

Prospective Feasibility Trial of Sentinel Lymph Node Biopsy in the Setting of Inflammatory Breast Cancer

Background

Most inflammatory breast cancer (IBC) patients have axillary disease at presentation. Current standard is axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NACT). Advances in NACT have improved pathologic complete response (pCR) rates increasing interest in performing sentinel lymph node (SLN) biopsy (SLNB). Previous studies on SLNB for IBC patients did not assess nodal response with imaging or use dual tracer mapping. We sought to prospectively determine false negative rates of SLNB in IBC patients using dual tracer mapping, and to correlate pathology with preoperative axillary imaging.

Enhanced Axillary Evaluation Using Reflector-Guided Sentinel Lymph Node Biopsy: A Prospective Feasibility Study and Comparison With Conventional Lymphatic Mapping Techniques

Background

Recently there are efforts to use sentinel lymph node biopsy (SLNB) techniques after neoadjuvant chemotherapy (NAC) to minimize axillary surgery. However, studies have shown higher false negative rates in this scenario, which might result in inaccurate assessment of treatment response and patient prognosis as well as leaving residual disease behind. In this study, we describe the use of reflector-guided excision of the percutaneously biopsied node (PBN) as an aid to conventional SLNB and its predictor of the axillary status after NAC.

Expanding Implementation of ACOSOG Z0011 in Surgeon Practice

Background

After publication of American College of Surgeons Oncology Group (ACOSOG) Z0011, surgeons at our institution limited axillary surgery to sentinel lymph node dissection (SLND) in 76% of patients meeting trial eligibility criteria. Our study objective was to assess incorporation of the trial data into practice 5 years later.

Accuracy of sentinel lymph node biopsy after neo-adjuvant chemotherapy in patients with locally advanced breast cancer and clinically positive axillary nodes

Background

Feasibility and accuracy of sentinel node biopsy (SLNB) after the delivery of neo-adjuvant chemotherapy (NAC) is controversial. We here report our experience in NAC-treated patients with locally advanced breast cancer and clinically positive axillary nodes, and compare it with the results from our previous randomized trial assessing SLNB in early-stage breast cancer patients.

Patients and methods

Sixty-four consecutive patients with large infiltrating tumor and clinically positive axillary nodes received NAC and subsequent lymphatic mapping, SLNB and complete axillary lymph node dissection (ALND). The status of the sentinel lymph node (SLN) was compared to that of the axilla.

Results

At least one SLN was identified in 60 of the 64 patients (93.8%). Among those 60 patients, 37 (61.7%) had one or more positive SLN(s) and 23 (38.3%) did not. Two of the patients with negative SLN(s) presented metastases in other non-sentinel nodes. SLNB thus had a false-negative rate, a negative predictive value and an overall accuracy of 5.1%, 91.3% and 96.7%, respectively. All these values were similar to those we reported for SLNB in the settings of early-stage breast cancer.

Conclusion

SLNB after NAC is safe and feasible in patients with locally advanced breast cancer and clinically positive nodes, and accurately predicts the status of the axilla.     

Staging breast cancer by sentinel lymph node biopsy: Do patients with a single negative sentinel node (N=1) experience worse outcomes than those with multiple negative sentinel nodes (N>1)?

Background

Though sentinel lymph node biopsy (SLNB) is standard of care for early breast cancer, concern remains for false negative nodes and potential implications for understaging and under-treatment, particularly when only one sentinel node is retrieved. We examined whether patients with a single negative SLN (N?=?1) experience worse survival than those with two or more negative SLNs (N?>?1).

Application of ACOSOG Z1071: Effect of Results on Patient Care and Surgical Decision-Making

Background

The ACOSOG (American College of Surgeons Oncology Group) Z1071 assessed the feasibility of performing sentinel lymph node biopsy (SLNB) in node-positive patients who completed neoadjuvant chemotherapy (NACT). Historically, adoption of clinical research into practice takes years. The goal of this study was to determine the effect of Z1071 on our practice.

Sentinel lymph node biopsy after previous axillary surgery: A review

Background

The utility of axillary lymph node dissection (ALND) in the management of breast cancer is currently under close scrutiny. At primary diagnosis the use of sentinel lymph node biopsy (SLNB) has restricted ALND for proven nodal disease, however the management of the axilla at local (in-breast) relapse is less clearly defined with many undergoing routine ALND. This review examines the role of SLNB in the re-operative setting with the objective of developing an axillary management algorithm for use at in-breast local relapse, and restricting ALND to node-positive recurrent cancers.

Methods

We reviewed published reports of SLNB at local relapse in women who had previously undergone axillary surgery either as lymph node biopsy, SLNB, axillary sampling (AS) or axillary lymph node dissection (ALND).

Results

There have been no randomised trials. Six reports with 327 cases were identified; of which 61% (199/327) had previous SLNB or ALND with <9 nodes removed. There was an overall successful sentinel lymph node (SLN) localisation at re-operation of 69% (227/327), range of 51-100%. In patients who have previously had limited axillary surgery (<9 nodes removed), the rate of successful SLN localisation was 83% (165/199), range of 68-100% and 142/165 (86%, range 80-100%) were node negative. In these highly selected patients no axillary recurrences were noted in those who had a negative SLN at re-operation after 26-46 months follow up.

Conclusion

SLNB at in-breast relapse is feasible and safe with successful localisation related to the extent of previous axillary surgery.     

腋窝逆向淋巴示踪预防乳腺癌患者上肢淋巴水肿的研究

目的：探讨乳腺癌前哨淋巴结活组织检查（ SLNB）或腋窝淋巴结清扫（ ALND）过程中,进行腋窝逆向淋巴示踪（ ARM）以保留引流上肢淋巴液的腋窝淋巴结的可行性,及其对术后上肢淋巴水肿的预防作用。方法选择2012年1月至2013年6月本科71例全乳房切除术＋前哨淋巴结活组织检查术患者（ SLNB组）和134例乳腺癌改良根治术患者（ ALND组）进行临床研究。将SLNB组和ALND组分别随机分为对照组和示踪组,即：SLNB对照组36例,SLNB示踪组35例;ALND对照组64例,ALND示踪组70例。 SLNB示踪组和ALND示踪组的手术方式除与其对照组相同外,还需进行ARM以保留引流上肢淋巴液的腋窝淋巴结（ ARM淋巴结）。前哨淋巴结和ARM淋巴结定位方法如下：术前2 h,在患者乳房肿块周围及患侧上臂内侧皮下注射^99Tc^m-Dx标记的同位素,并于术前5 min在患侧上臂内侧皮下注射2 ml亚甲蓝进行ARM淋巴结显色,术中用同位素γ探测仪探测放射性核素热点进行前哨淋巴结定位,并用γ探测仪结合蓝色染料定位ARM淋巴结。术中注意观察ARM淋巴结蓝染情况及其与前哨淋巴结有无重合,若无重合则保留所有蓝染的ARM淋巴结,若有重合则同时切除前哨淋巴结和ARM淋巴结;术后统计切除的淋巴结数量、术中出血量、置管时间、引流液体量及手术时间。术后6个月随访两组患者上肢淋巴水肿的发生情况。定量资料分析采用 t检验,定性资料比较采用秩和检验或χ^2检验。结果在SLNB示踪组35例患者中,26例（74．29%,26/35）术中检测到ARM淋巴结,其中1例患者前哨淋巴结与ARM淋巴结重合,此患者在SLNB过程中也接受了ARM淋巴结切除,因此SLNB示踪组ARM淋巴结保留率为71．43%（25/35）。在ALND示踪组70例患者中,67例（95．71%,67/70）术中检测到ARM淋巴结,其中5例患者前哨淋巴结与ARM淋巴结重合,此部分患者在ALND过程中同时接受ARM淋巴结切除,因此ALND示踪组ARM淋巴结保留率为88．57%（62/70）。在SLNB对照组与SLNB示踪组之间以及ALND对照组与ALND示踪组之间,腋窝淋巴结切除数量、术中出血量、术后引流液体量及置管时间的差异均无统计学意义（ t=-1．136、-0．570、0．032、0．903,P=0．264、0．570、0．975、0．370;t=1．149、0．416、1．405、-0．547,P=0．253、0．678、0．162、0．585）,但是SLNB示踪组和ALND示踪组的手术时间均长于其对照组[（90．26±6．04） min比（86．61±5．62） min,t=-2．616,P=0．011;（112．24±7．94） min比（92．33±6．88） min,t=-15．399,P=0．000]。术后随访6个月：SLNB对照组与SLNB示踪组上肢淋巴水肿发生率分别为11．11%（4/36）和8．00%（2/25）,两者间差异无统计学意义（P=1．000）;ALND对照组与ALND示踪组上肢淋巴水肿发生率分别为31．25%（20/64）和6．45%（4/62）,两者间差异有统计学意义（χ2=12．560,P=0．000）。结论乳腺癌患者行SLNB或ALND的过程中可以行ARM。 SLNB过程中保留ARM淋巴结对降低术后上肢淋巴水肿发生率无意义,而ALND过程中保留ARM淋巴结可有效降低术后上肢淋巴水肿发生率。     

Wire localization of clip-marked axillary lymph nodes in breast cancer patients treated with primary systemic therapy

Introduction

Clipping and selective removal of initially suspicious axillary lymph nodes in breast cancer patients who have been sonographically down-staged by primary systemic therapy improves the accuracy of surgical staging and provides the opportunity for more conservative axillary surgery. This study evaluated whether preoperative ultrasound-guided wire localization of the clipped node is useful for routine clinical practice.

Clinical Significance of the Axillary Arch in Sentinel Lymph Node Biopsy

Purpose

The axillary arch is an anomalous muscle that is not infrequently encountered during axillary sentinel lymph node biopsy (SLNB) of breast cancer patients. In this study, we aimed to investigate how often the axillary arch is found during SLNB and whether it affects the intraoperative sentinel lymph node (SLN) identification rate.

Methods

We retrospectively analyzed the correlation between the presence of the axillary arch and the SLN sampling failure rate during SLNB in 1,069 patients who underwent axillary SLNB for invasive breast cancer.

Results

Of 1,069 patients who underwent SLNB, 79 patients (7.4%) had the axillary arch present. The SLNB failure rate was high when the patient''s body mass index was ≥25 (p=0.026), when a single SLN mapping technique was used (p=0.012), and when the axillary arch was present (p<0.001). These three factors were also found to be statistically significant by multivariate analysis, and of these three factors, presence of the axillary arch most significantly increased the SLNB failure rate (hazard ratio, 10.96; 95% confidence interval, 4.42-27.21; p<0.001). Additionally, if the axillary arch was present, the mean operative time of SLNB was 20.8 minutes, compared to 12.5 minutes when the axillary arch was not present (p<0.001). If the axillary arch was present, the SLN was often located in a high axillary region (67%) rather than in a general low axillary location.

Conclusion

The axillary arch was found to be a significant factor affecting intraoperative SLN failure rate. It is necessary to keep in mind that carefully checking the high axillar region during SLNB in breast cancer patients with the axillary arch is important for reducing SLN sampling failure.     

Persistent pain,sensory disturbances and functional impairment after immediate or delayed axillary lymph node dissection

Background

Patients treated with 2-step axillary lymph node dissection (ALND) may be at increased risk of nerve damage due to more challenging surgery than an ALND immediately after a sentinel lymph node biopsy (SLNB), and thus more at risk for persistent pain after breast cancer treatment (PPBCT). The aim of this study was to examine PPBCT, sensory disturbances and functional impairment in patients treated with a 2-step ALND compared to patients with an SLNB followed by an immediate ALND, and patients with ALND without a prior SLNB.

Methods

The study is a cross-sectional questionnaire study, comparing 2847 women treated with ALND in Denmark in 2005–2008. 196 patients treated with a 2-step ALND were compared with 1558 patients treated with an ALND after SLNB and 1093 with an ALND without a prior SLNB.

Results

Overall prevalence of PPBCT and sensory disturbances was high, with about 55% reporting PPBCT and 77% reporting sensory disturbances in all groups. No differences were found between the groups on prevalence and intensity of PPBCT (p = 0.92), sensory disturbances (p = 0.32), and functional consequences (p = 0.35).

Conclusions

A 2-step ALND does not modify the risk of developing PPBCT compared to an immediate ALND.     

Sentinel lymphadenectomy for the staging of clinical axillary node-negative breast cancer before neoadjuvant chemotherapy

Background

Several authors reported sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NC). Nevertheless, the ideal time of SLNB is still a matter of debate.

Methods

We evaluated the feasibility and the accuracy of SLNB before NC using a combined procedure (blue dye and radio-labelled detection) before NC. Axillary lymph node dissection (ALND) was performed after completion of NC in a homogeneous cohort study with clinically axillary node-negative breast cancer.

Results

Among the 20 women who had metastatic SLNB (65%), 4 (20%) had additional metastatic node on ALND. By contrast, all the 11 women who had no metastatic SLNB had no involved nodes in the ALND. The SLN identification rate before NC was 100% with any false negative.

Conclusions

SLNB before NC is a feasible and an accurate diagnostic tool to predict the pre-therapeutic axilla status. These findings suggest that ALND may be avoided in patients with a negative SLNB performed before NC.     

Feasibility of Sentinel Lymph Node Biopsy in Breast Cancer Patients with Initial Axillary Lymph Node Metastasis after Primary Systemic Therapy

Purpose

Primary systemic therapy (PST) downstages up to 40% of initial documented axillary lymph node (ALN) metastases in breast cancer. The current surgical treatment after PST consists of breast tumor resection and axillary lymph node dissection (ALND). This strategy, however, does not eliminate unnecessary ALND in patients with complete remission of axillary metastases. The aim of this study was to examine the accuracy of sentinel lymph node biopsy (SLNB) after PST among patients with documented ALN metastasis at presentation and to identify the rate of pathologic complete-remission (CR) with ALN after PST.

Methods

We analyzed 66 patients with ALN metastasis that was pathologically proven preoperatively who underwent SLNB and concomitant ALND after PST. Axillary ultrasound (AUS) was used to evaluate the clinical response of initially documented ALN metastasis after PST. Intraoperative lymphatic mapping was performed using blue dye with or without radioisotope.

Results

After PST, 34.8% of patients had clinical CR of ALN on AUS and 28.8% patients had pathologic CR of ALN. The overall success rate of SLNB after PST was 87.9%, and the sentinel lymph node identification rate in patients with clinical CR was 95.7%. In patients with successful lymphatic mapping, 70.7% of patients had residual axillary metastases. The overall accuracy and false-negative rate were 87.9% and 17.1% in all patients: 95.5% and 10.0% in patients with clinical CR of ALN, and 83.3% and 19.4% in patients with residual axillary disease after PST.

Conclusion

Our findings suggest that SLNB may be feasible in patients with initial documented ALN metastasis who have clinical CR for metastatic ALN after PST. Further investigation in a prospective setting should be performed to confirm our results.     

The Shift From Sentinel Lymph Node Biopsy Performed Either Before or After Neoadjuvant Systemic Therapy in the Clinical Negative Nodes of Breast Cancer Patients. Results,and the Advantages and Disadvantages of Both Procedures

Background

In patients with breast cancer who are candidates for neoadjuvant therapy (NAT), the timing of when to perform sentinel lymph node biopsy (SLNB) remains under discussion. The aim of this study was to compare the advantages and disadvantages of SLNB performed before and after NAT.

A differential intra-operative molecular biological test for the detection of sentinel lymph node metastases in breast carcinoma. An extended experience from the first UK centre routinely offering the service in clinical practice

Introduction

One-Step Nucleic acid Amplification (OSNA) is a molecular biological assay of cytokeratin-19 (a breast epithelial marker) mRNA. It can be employed intra-operatively for detection of lymph node metastases in breast carcinoma. Patients with positive sentinel nodes may proceed to axillary lymph node dissection (ALND) level I or higher dependent upon the OSNA quantitative result, during the same surgical procedure, avoiding a second operation and eliminating the technical difficulties possibly associated with delayed ALND.

Aims

Our Breast Unit was the first in the UK to implement this novel technique in routine practice. This study reviews our first 44-month data following introduction of OSNA “live” on whole sentinel nodes following an extensive validation study (Snook et al.).⁹

Methods

Data was collected prospectively from the period of introduction 01/12/2008 to 30/08/2012. All patients eligible for sentinel node biopsy were offered OSNA and operations were performed by five consultant breast surgeons. On detection of macro-metastasis a level II/III and for a micro-metastasis a level I ALND was performed.

Results

A total of 859 patients (1709 sentinel lymph nodes) were analysed. All except one were females. The majority underwent wide local excision (73.4%, n = 631) or mastectomy 25% (n = 215) and 1.6% (13) underwent SLN biopsy alone. IDC was seen in 79% (n = 680) of the patients and 53.5% (n = 460) had grade II tumours. One-third (30.8%, n = 265) had positive sentinel nodes and had further axillary surgery at the time of SLN biopsy. Of these, 47% (n = 125/265) had macro-metastases, 38% (n = 101/265) had micro-metastases and 14.7% (n = 39/265) had “positive but inhibited” results. Positive non-sentinel lymph nodes (NSLN) were seen in 35% (44/125) of those with macro-metastases; 17.8% (18/101) of the patients with micro-metastases and 10.2% (4/39) of the “positive but inhibited” group.

Conclusion

In our series over a third of our patients had positive lymph nodes detected with OSNA allowing them to proceed directly to axillary surgery at the same operation. This technique eliminates the need for a second operation in sentinel lymph node positive patients and avoids the anxiety waiting for histological results.     

Staging and management of axillary lymph nodes in patients with local recurrence in the breast or chest wall after a previous negative sentinel node procedure

Objective

To evaluate axillary staging and management in patients with local recurrence (LR) after a previous negative sentinel lymph node biopsy (SNB).

Methods

Between 1999 and 2008, 130 patients with previous negative SNB developed a LR of breast or chest wall. After examination of clinical records, 70 patients met the inclusion criteria and remained available for analysis.

Results

Thirty-seven patients were treated with axillary lymph node dissection (ALND), followed by axillary radiotherapy in 9 cases. In 26 of these 37 patients no positive axillary lymph nodes were found. Nineteen patients received no treatment of the axilla at all. Of those, 9 were older than 70 years of age at diagnosis of LR. In 13 patients a second SNB was attempted, but was successful in only 5 cases. Eight patients underwent a complementary ALND. Overall, positive lymph nodes were detected in 13 of the 50 patients who underwent axillary staging, either by SNB or ALND. The median length of follow-up of the 70 patients following their diagnosis of LR was 24 months (range 2–81 months). During this follow-up period one patient developed an axillary recurrence. This was a patient who refused to undergo ALND but was given locoregional radiotherapy instead.

Conclusions

In the absence of guidelines for staging and management of the axilla at time of LR of breast or chest wall, many different strategies are being used. Considering the high rate of positive axillary lymph nodes in these patients, repeat surgical staging is appropriate.     

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.