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.

Sentinel lymph node biopsy after neoadjuvant chemotherapy

BACKGROUND: We surveyed single-center and multi-center studies pertaining to sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy to compare the results with those of our current study to evaluate the feasibility and accuracy of SLNB after neoadjuvant chemotherapy. METHODS: From October 2001 to July 2003, 80 patients who had neoadjuvant chemotherapy underwent curative surgery and axillary lymph node dissection (ALND) after SLNB at the Center for Breast Cancer, National Cancer Center. A MEDLINE search was performed using the keywords breast cancer, sentinel lymph node biopsy, and neoadjuvant chemotherapy. RESULTS: Our results showed that 42 (52.6%) of 80 patients had downstaging of the primary tumor; 9 patients (11.3%) had pathologic complete response (pCR) and 33 (41.3%) had pathologic partial response (pPR). 26 patients (32.5%) showed complete axillary clearance after neoadjuvant chemotherapy. Among them, 5 patients (6.3%) revealed pCR of both the primary tumor and axillary metastasis. SLNB was successful in 61 of 80 patients (76.3%) and there were 3 false negatives, yielding a false negative rate (FNR) of 7.3% (3/41), a negation prediction value (NPV) of 87.0%(20/23), and an accuracy of 95.1% (58/61). Thirteen out of 16 studies retrieved by to MEDLINE pertaining SLNB after neoadjuvant chemotherapy concluded its feasibility and accuracy with a identification rate of 82%-100% and a FNR of 17-100%. CONCLUSION: Most studies, including ours, concluded that SLNB after neoadjuvant chemotherapy is accurate and could be an alternative to ALND.     

Population based study on sentinel node biopsy before or after neoadjuvant chemotherapy in clinically node negative breast cancer patients: Identification rate and influence on axillary treatment

The timing of the sentinel lymph node biopsy (SNB) is controversial in clinically node negative patients receiving neoadjuvant chemotherapy (NAC). We studied variation in the timing of axillary staging in breast cancer patients who received NAC and the subsequent axillary treatment in The Netherlands.Patients diagnosed with clinically node negative primary breast cancer between 1st January 2010 and 30th June 2013 who received NAC and SNB were selected from the Netherlands Cancer Registry. Data on patient and tumour characteristics, axillary staging and treatment were analysed. Two groups were defined: (1) patients with SNB before NAC (N = 980) and (2) patients with SNB after NAC (N = 203).Eighty-three percent of patients underwent SNB before NAC, with large regional variation (35–99%). The SN identification rate differed for SNBs conducted before and after NAC (98% versus 95%; p = 0.032). A lower proportion of patients had a negative SNB when assessed before NAC compared to after (54% versus 67%; p = 0.001). The proportion of patients receiving any axillary treatment was higher for those with SNB before NAC than after (45% versus 33%; p = 0.006).In conclusion, variation exists in the timing of SNB in clinical practice in The Netherlands for clinically node negative breast cancer patients receiving NAC. The post-NAC SN procedure is, despite some lower SN identification rate, associated with a significantly less frequent axillary treatment and thus with less expected morbidity. The effect on recurrence rate is not yet clear. Patients in this registry will be followed prospectively for long-term outcome.     

Sentinel node biopsy after primary chemotherapy in cT2 N0/1 breast cancer patients: Long-term results of a retrospective study

Background

It is controversial whether sentinel node biopsy (SNB) is adequate in breast cancer patients who become cN0 after primary chemotherapy. To address this we retrospectively compared outcomes in T2 cases given primary chemotherapy, comparing those given axillary dissection (AD) with those given SNB but no AD if sentinel nodes were clinically negative post-chemotherapy.

Omission of axillary lymph node dissection in patients with ypN+ breast cancer after neoadjuvant chemotherapy: A retrospective multicenter study (KROG 21-06)

BackgroundWe evaluated the impact of omitting axillary lymph node dissection (ALND) on oncological outcomes in breast cancer patients with residual nodal disease after neoadjuvant chemotherapy (NAC).MethodsThe medical records of patients who underwent NAC followed by surgical resection and had residual nodal disease were retrospectively reviewed. In total, 1273 patients from 12 institutions were included; all underwent postoperative radiotherapy. Axillary surgery consisted of ALND in 1103 patients (86.6%) and sentinel lymph node biopsy (SLNBx) alone in 170 (13.4%). Univariate and multivariate analyses of disease-free survival (DFS) and overall survival (OS) were performed before and after propensity score matching (PSM).ResultsThe median follow-up was 75.3 months (range, 2.5–182.7). Axillary recurrence rates were 4.8% in the ALND group (n = 53) and 4.7% in the SLNBx group (n = 8). Before PSM, univariate analysis indicated that the 5-year OS rate was inferior in the ALND group compared to the SLNBx group (86.6% vs. 93.3%, respectively; P = 0.002); multivariate analysis did not show a difference between groups (P = 0.325). After PSM, 258 and 136 patients were included in the ALND and SLNBx groups, respectively. There were no significant differences between the ALND and SLNBx groups in DFS (5-year rate, 75.8% vs. 76.9%, respectively; P = 0.406) or OS (5-year rate, 88.7% vs. 93.1%, respectively; P = 0.083).ConclusionsSLNBx alone did not compromise oncological outcomes in patients with residual nodal disease after NAC. The omission of ALND might be a possible option for axillary management in patients treated with NAC and postoperative radiotherapy.     

Sentinel lymph node biopsy in breast cancer: an overview of the Japanese experience

This paper reviews the Japanese literature regarding sentinel lymph node (SLN) biopsy in an attempt to provide an overview of existing controversies and to suggest a method for the identification of the SLN and the detection of micrometastases in the SLN to eliminate unnecessary axillary lymph node dissection (ALND). The combined dye- and gamma probe-guided method resulted in the accurate identification of the SLN in 96% of patients, compared with 80% when the dye-guided method alone was used. Although neither 99m-Tc sulfur colloid nor 99m-Tc colloidal albumin is commercially available in Japan, 99m-Tc stannous phytate and 99m-Tc rhenium colloid appear to be ideal tracers for identifying SLNs. Moreover, subdermal injection over the primary tumor or subareolar injection was found to enhance SLN identification, although these injection routes do not lead to detection of internal mammary SLNs. Furthermore, the accuracy of SLN diagnosis using frozen sections as well as imprint cytology improved with an increase in the number of sections, and could attain a sensitivity comparable to that obtained with routine histologic examination of permanent sections. As a result, several surgeons have begun to offer the option of forgoing ALND to patients with negative SLN. Although subsequent relapse in the axilla has not yet been reported, longer follow-up periods are needed to assess accurately the incidence of axillary failure in these negative SLN patients.     

精准治疗理念下乳腺癌患者腋窝淋巴结的评估与处理

腋窝淋巴结状态是乳腺癌分期、治疗决策以及预后判断的重要依据。精准医疗时代的到来更突显了腋窝淋巴结状态评估的重要性。除查体、超声等常规检查外,乳腺核磁、PET/CT以及近红外荧光、超顺磁性氧化铁、光声造影剂等新方法也可提供指导,其中前哨淋巴结活检是最重要的检查方法。新的临床证据表明前哨淋巴结阴性和前哨淋巴结1~2枚阳性的患者可以免除腋窝淋巴结清扫。炎性反应指标的比值可能是预测淋巴结转移的有用指标。部分高龄患者可以免除腋窝手术并获得良好预后。本文将围绕腋窝淋巴结的评估方法和处理争议进行梳理和总结,以期为精准治疗理念下乳腺癌患者腋窝淋巴结的处理提供新的指导。     

Controversies and recommendations regarding sentinel lymph node biopsy in primary breast cancer: A comprehensive review of current data

In primary breast cancer, sentinel lymph node biopsy has been established as the gold standard for regional axillary staging. A robust body of randomized data support its accuracy and safety in patients with early, clinically node negative disease. However, the role of SLNB remains debatable in various patient subgroups, and recent advances in histopathology, dedicated axillary ultrasound imaging and chemotherapy regimens, put its role under a new perspective. Herein, we review the current literature data on the indications for SLNB and discuss the challenges in management germane to special patient subgroups and patterns of disease. We also present emerging data on the optimal management of the SLN+ patient, in light of recent trials challenging the dogma of completion axillary dissection after a positive sentinel node biopsy.     

Avoidance of axillary lymph node dissection in selected patients with node-positive breast cancer

Aims

Currently, it is standard practice to avoid ALND in patients with negative SLN, whereas this procedure is mandated for those with positive SLN. However, there has been some debate regarding the necessity of complete ALND in all patients with positive SLN. This review article discusses the issues related to eliminating the need for ALND in selected patients with positive nodes.

Methods

A review of the English language medical literature was performed using the MEDLINE database and cross-referencing major articles on the subject, focusing on the last 10 years.

Results

Currently, complete ALND is mandated in patients with SLN macrometastases as well as those with clinically positive nodes. It is not clear whether SLN biopsy is appropriate for axillary staging in patients with initially clinically positive nodes (N1) that become clinically node-negative (N0) after neoadjuvant chemotherapy. Although there is debate regarding whether ALND should be performed in patients with micrometastases in the SLN, it seems premature to abandon ALND in clinical practice. Moreover, it remains unclear whether it is appropriate to avoid complete ALND in patients with ITC-positive SLN alone.

Conclusions

In the absence of data from randomised trials, the long-term impact of SLN biopsy alone on axillary recurrence and survival rate in patients with SLN micrometastases as well as those with ITC-positive SLN remains uncertain. These important issues must be determined by careful analysis of the results of ongoing clinical trials.     

Sentinel lymph node biopsy without axillary dissection after an intraoperative negative histological investigation in 358 invasive breast cancer cases

BACKGROUND: Sentinel lymph node biopsy (SLNB) is an important treatment option for breast cancer patients, as it can accurately predict axillary status. Our previous study using dye with or without radioisotope showed the accuracy and sensitivity of SLNB to be 97% and 94%, respectively. Based on these results, axillary lymph node dissection (ALND) was eliminated starting in January, 1999 in patients with intraoperatively negative SLNB at our institution. The present study shows the results and outcomes of SLNB as a sole procedure for patients with invasive breast cancer. PATIENTS AND METHODS: Three-hundred-fifty-four patients and 358 cases of invasive breast cancer (4 bilateral breast carcinoma) treated with SLNB alone after an intraoperative negative SLNB were studied prospectively from January 1999 to December 2001. RESULTS: The number of the identified SLNs per case ranged from 1 to 8 (mean, 2.5). Of a total of 358 cases, 297 (83%) were treated with hormone therapy and/or chemotherapy, and 281 (78%) were treated with radiotherapy to the conserved breast (50 Gy+/-10 Gy boost), the axilla (50 Gy), or the both sites. After a median follow-up of 21 (range 6-42) months, no patient developed an axillary relapse. Four cases initially recurred in distant organs and one case in the conserved breast. CONCLUSIONS: Our results indicate that an intraoperative negative SLNB without further ALND may be a safe procedure when strict SLNB is performed. To better assess the safety, however, may require longer follow-up.     

Sentinel node biopsy to avoid axillary lymph node dissection in breast cancer

The role of sentinel node biopsy in breast cancer has increased over the last few years. Sentinel nodes can predict the status of all axillary lymph nodes precisely and select patients with negative nodes for whom axillary dissection is unnecessary. Many problems remain, such as the ideal injection technique, ideal agents, and ideal histological detection of sentinel node metastases, and must be addressed before sentinel node biopsy becomes the standard of care for patients with breast cancer.     

Sentinel node biopsy in breast cancer

Axillary lymphnode dissection (ALND) for breast cancer patients provides local control and information for the determination of the type of adjuvant therapy. The benefit of axillary surgery itself for survival is considered to be limited to patients with positive nodes. Sentinel node biopsy is a recently developed, minimally invasive technique for precisely predicting axillary nodal status. As this technique has less morbidity and greater accuracy than ALND, it replaces ALND for patients with node negative breast cancer. In this report, we outline the current status of sentinel node biopsy for breast cancer patients and introduce our preliminary results.     

Controversies in sentinel node biopsy for breast cancer

Sentinel node biopsy for breast cancer patients has recently been applied as a less invasive, highly accurate alternative to axillary lymph node dissection. Numerous studies have shown that sentinel nodes accurately diagnose axillary staging. However, many problems remain to be answered and must be addressed before sentinel node biopsy becomes the standard surgical procedure for patients with breast cancer. We reviewed and discussed here three of these problems; axillary sampling as an alternative to sentinel node biopsy, dye method vs. combination of dye and radiocolloid for sentinel node biopsy, and intraoperative sentinel node examination. Further investigation will continue to be necessary as we learn how to better provide procedure of sentinel node biopsy.     

Feasibility and validation of the targeted axillary dissection technique in the axillary staging of breast cancer after neoadjuvant therapy: Definitive results

Aimto study the feasibility and value of “Targeted Axillary Dissection” (TAD) in cN1 breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NACT), in order to avoid unnecessary axillary lymph node dissection (ALND).Materials and methodsDesign: Prospective observational study. Inclusion criteria: Patients with histologically confirmed cN1 staging BC and treated with NACT between January 2016 and August 2019 who accomplished clinical response. Method: Fine-Needle Aspiration (FNA) positive axillary nodes were marked with a metallic clip prior to neoadjuvant treatment. All patients were summited to TAD and ALND. Analysis of data: We performed [1]: a feasibility analysis of clinical, radiological and pathological variables, as well as difficulties and complications of the TAD [2]; a diagnostic test study of the sentinel lymph node biopsy (SLNB), clipped lymph node biopsy (BCLIP) and their combination (TAD), using ALND as the Gold Standard.Results60 patients were included. 43 patients (71.7%) had a complete clinical lymph node response to NACT. Neither limitations nor complications in clip placement were found. Intraoperative location of the clipped node was problematic in 7 cases (11.7%). The pathological complete response rate (pCR) was 30.5% (18 patients) and ypN0 staging rate was 38.3% (23 patients). Sensitivity values of each technique were: SLNB: 80.9% (95%CI: 61.8–100); BCLIP: 80.8% (95%CI: 63.7–97.8); TAD: 92.6% (95%CI: 80.9–100) with negative predictive values of: SLNB: 84.6% (95%CI: 68.8–100); BCLIP: 81.0% (95%CI: 63.7–97.8); TAD: 91.3% (95%CI: 77.6–100).ConclusionTAD is feasible and valid to rule out axillary metastatic involvement in cN1 breast cancer patients who respond to NACT.     

早期乳腺癌前哨淋巴结活检替代腋窝淋巴结清扫的临床应用研究

目的 对前哨淋巴结活检(sentinel lymph node biopsy,SLNB)替代腋窝淋巴结清扫(axillary lymph node dis-section,ALND)在早期乳腺癌患者中的应用以及安全性研究及探讨.方法 回顾性分析行SLNB和ALND手术的503例早期乳腺癌病例,对患者住院时间、拔管时间及住院费用进行对比,以及对患者上肢并发症、腋窝局部复发及远处转移情况进行随访,随访至2016年06月,中位随访时间为32(6 ～52)个月.结果 在住院时间、拔管时间、住院费用以及上肢并发症方面,SLNB组明显优于ALND组,差异有统计学意义,而在腋窝局部复发及远处转移情况方面两组无统计学意义.结论 在SLN阴性早期乳腺癌中,SLNB与ALND可以取得相同的疗效,而且,SLNB与ALND相比,手术创伤小,麻木疼痛、肩关节活动受限等术后并发症明显减少,且可缩短患者住院时间,减轻患者的经济负担.     

乳腺癌新辅助化疗后腋窝淋巴结病理学完全缓解预测模型的验证与改良研究

背景与目的：新辅助化疗（neoadjuvant chemotherapy,NAC）是局部晚期乳腺癌患者的标准治疗模式,2018年有研究报道了一个多变量预测模型,用于预测临床腋窝淋巴结阳性（clinical lymph node-positive,cN₊）患者NAC后腋淋巴结病理完全缓解（ypN₀）的概率。分析乳腺癌NAC后ypN₀的相关因素,验证Olga Kantor预测模型的临床应用价值。方法：纳入山东大学附属山东省肿瘤医院2014年4月—2018年5月收治的350例临床腋淋巴结阳性NAC后行腋窝淋巴结清扫术（axillary lymph node dissection,ALND）的患者,并进行Olga Kantor预测模型的验证;由于该模型采用术后病理学评估乳腺原发肿瘤反应无助于术前预测ypN₀,因此采用术前影像评价替代术后病理学评估进行改良,分别分析验证模型和改良模型的独立预测因素,计算受试者工作特征（receiver operating characteristic,ROC）曲线的曲线下面积（area under curve,AUC）评估两模型的预测效能。结果：验证模型中年龄、分型分组及病理乳房原发肿瘤反应为ypN0的独立预测指标,改良模型中年龄、分型分组及临床乳房原发肿瘤反应为ypN₀的独立预测指标（P均＜0.05）。验证模型及改良模型的AUC分别为0.788和0.782（P>0.05）。改良模型分数≤3分、4~7分及≥8分患者NAC后ypN₀概率分别为2.5%（1/40）、22.4%（51/228）和68.3%（56/82）。结论：Olga Kantor预测模型可以较为准确地评估cN+患者ypN₀概率,改良模型具有同等的预测效能且更贴合临床实际,有助于NAC后腋窝处理模式的合理选择：得分≤3分推荐直接行ALND,4~7分可选择前哨淋巴结活检（sentinel lymph node biopsy,SLNB）,≥8分推荐行SLNB。     

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.

Patterns of Failure in Women Who Have Residual Nodal Disease After Neoadjuvant Chemotherapy for Breast Cancer According to Extent of Lymph Node Surgery

BackgroundOptimal surgical management of limited axillary nodal disease following neoadjuvant chemotherapy (NAC) for breast cancer is evolving. Concerns exist with respect to leaving residual disease in the axilla when omitting axillary lymph node dissection (ALND) in this setting. We sought to determine whether extent of nodal surgery altered patterns of failure and patient outcomes.Patients and MethodsWe identified 70 patients with breast cancer who were confirmed cN0 after NAC yet had residual nodal disease (ypN1) on sentinel lymph node biopsy (SLNB). Twenty-eight patients underwent SLNB alone and 42 underwent SLNB+completion (c)ALND in a non-randomized fashion. Most (n = 65) patients underwent adjuvant regional nodal irradiation (RNI). Detailed patterns of failure data were obtained for each patient.ResultsThe median follow-up was 43.5 months. There were 30 (43%) recurrences. Of these, 5 were isolated locoregional failures, and 24 were distant failures. There were no significant differences in local (P = .13), regional (P = .62), or distant (P = .47) failure between patients who underwent SLNB alone versus SLNB+cALND. Seventeen (24%) patients died. Overall survival was similar in both groups with median overall survival not reached for those who underwent SLNB and 109 months for those who underwent SLNB+cALND (P = .45).ConclusionsThere were no differences in patterns of recurrence among patients with 1 to 3 involved lymph nodes after NAC who underwent SLNB alone versus SLNB+cALND in the setting of RNI. We await the results of ongoing, prospective clinical trials to confirm the relative merits of RNI in lieu of cALND in these patients.     

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.