Reply to the letter on sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with node-positive breast cancer

Breast Cancer Research and Treatment -     

Sentinel lymph node biopsy in breast cancer patients after neoadjuvant chemotherapy

BACKGROUND AND OBJECTIVES: Sentinel lymph node biopsy (SLNB) is an accurate method for axillary staging in patients with early breast cancer. The aim of this study was to evaluate the accuracy and the feasibility of SLNB in breast cancer patients who had received preoperative (neoadjuvant) chemotherapy. METHODS: Patients with advanced breast cancer stage II or III who were treated with neoadjuvant chemotherapy were included in the study. Sentinel lymph node (SLN) identification and biopsy was attempted and performed, and axillary lymph node dissection (ALND) was performed in the same surgical procedure after SLNB. The histopathologic examination of the SLNs and the dissected axillary lymph nodes was performed and nodal status was compared. RESULTS: Thirty patients were included in the study. After peritumoural injection of technetium-99m labelled human albumin and subareolar subcutaneous injection of blue dye, the SLNs could be identified in 26/30 patients (identification rate 86.7%). In 4/30 patients (13.3%) SLNs could not be identified. In 25/26 patients (96.2%) SLNs accurately predicted the axillary status. Eleven patients had negative SLNs and negative nodes in ALND. Six patients had positive SLNs and positive nodes in ALND. In eight patients SLNs only were positive and nodes in ALND were negative. One patient had a false-negative SLNB, calculating a false-negative rate of 6.7% (1/15). CONCLUSIONS: SLNB is a well introduced technique for axillary staging in patients with early breast cancer. The accuracy of SLNB after neoadjuvant chemotherapy is similar to patients with primary surgery. SLNB could be an alternative to ALND in a subgroup of patients after neoadjuvant chemotherapy, and therefore could reduce morbidity due to surgery in those patients. Due to small numbers of patients, further evaluation in this subset of patients is required.     

前哨淋巴结活检术在乳腺癌手术中的应用

目的探讨乳腺癌手术治疗中前哨淋巴结活检术的应用价值。方法选取2013年2月至2016年12月间海南省中医院收治的80例接受乳腺癌手术治疗的患者,采用随机数表法分为观察组(接受前哨淋巴结活检术)与对照组(未接受前哨淋巴结活检术),每组40例。比较两组患者治疗前后血清肿瘤标志物水平和不良反应情况。结果治疗后观察组患者血清肿瘤标志物癌脴抗原(CEA)、糖类抗原(CA153)和糖类抗原(CA125)分别为(2.36±0.56)ng/ml、(13.21±5.53)U/ml和(15.64±5.43)U/ml,对照组患者分别为(3.28±0.86)ng/ml、(14.86±4.53)U/ml和(16.98±6.69)U/ml,两组均较治疗前明显降低,且观察组患者较对照组降低更多,差异均有统计学意义(均P<0.05)。对照组患者皮下积液、上肢水肿和上肢活动受限等并发症发生率合计为40.0%,观察组患者为7.5%,两组比较,差异有统计学意义(P<0.05)。结论前哨淋巴结活检辅助乳腺癌手术能够避免不必要的淋巴结清扫,减少机体损伤,降低不良反应发生率,且不会对手术效果造成影响,可在临床中推广。     

Neoadjuvant chemotherapy followed by surgery in gastric cancer patients with extensive lymph node metastasis

Gastric cancer with extensive lymph node metastasis (ELM) is usually considered unresectable and is associated with poor outcomes. Cases with clinical enlargement of the para-aortic lymph nodes and/or bulky lymph node enlargement around the celiac artery and its branches are generally dealt with as ELM. A standard treatment for gastric cancer with ELM has yet to be determined. Two phase II studies of neoadjuvant chemotherapy followed by surgery showed that neoadjuvant chemotherapy with S-1 plus cisplatin followed by surgical resection with extended lymph node dissection could represent a treatment option for gastric cancer with ELM. However, many clinical questions remain unresolved, including the criteria for diagnosing ELM, optimal regime, number of courses and extent of lymph node dissection.     

Sentinel lymph node biopsy in breast cancer patients treated with neoadjuvant chemotherapy

BACKGROUND:

Sentinel lymph node biopsy (SLNB) is a widely used staging method for patients with early breast cancer. Neoadjuvant chemotherapy modifies the anatomical conditions in the breast and axilla, and thus SLNB remains controversial in patients treated preoperatively. The aim of this study was to demonstrate the reliability and accuracy of this procedure in this particular group of patients.

METHODS:

The retrospective study analyzed medical records of patients diagnosed with primary breast cancer between the years 2005 and 2009. Of the patients treated by neoadjuvant therapy, 343 underwent lymphatic mapping to identify sentinel lymph nodes, and these were included in the analysis.

RESULTS:

The overall detection rate of sentinel lymph nodes was 80.8%. It was strongly influenced by clinical lymph node status (significantly higher success rate in lymph node‐negative patients); higher detection rates were also associated with age <50 years, estrogen receptor positivity, lower proliferation index, and absent lymphovascular space invasion. The false‐negative rate was 19.5% and was only marginally significantly dependent on lymphovascular space invasion. The overall accuracy of the method was 91.5%.

CONCLUSIONS:

By using the present technique, sentinel lymph node biopsy cannot be recommended as a reliable predictor of axillary lymph node status when performed at the authors' institution after neoadjuvant chemotherapy. Infrequent use of blue dye for lymphatic mapping, low number of resected sentinel lymph nodes, and absence of any selection among patients included in the study could be the main factors responsible for the low detection rate and high false‐negative rate. Cancer 2011;. © 2011 American Cancer Society.     

Sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with node-positive breast cancer: guiding a more selective axillary approach

Breast Cancer Research and Treatment -     

Sentinel lymph node biopsy in breast cancer patients with previous breast augmentation surgery

The number of breast augmentation surgeries (BAS) has increased. Therefore, the number of breast cancer patients with history of BAS has also increased. In this paper, we present two cases of sentinel lymph node biopsy (SLNB) in patients with previous BAS who were diagnosed with breast cancer. The patients were augmented using different approach; the first case was augmented through transaxillary incision, whereas the second case was augmented through periareolar incision. Lymphoscintigraphy (LPG) was performed on the patients 1 day prior to operation, enabling confirmation of lymphatic flow and SLN in both patients. SLNB was successfully performed in both cases. In one patient, SLNB was performed using indocyanine green (ICG) fluorescence and the Photodynamic Eye (PDE) system. Regardless of history of BAS, ICG and PDE system showed lymphatic flow and SLN in real time. LPG and ICG fluorescence were useful methods for SLN detection in patients with previous BAS, being able to confirm lymph flow before operation. Biopsy methods using LPG and PDE system were considered useful for difficult confirmation of lymph flow after breast augmentation. This is the first report of SLNB using ICG and PDE system for patients with previous BAS.     

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.     

乳腺癌新辅助化疗后内乳区前哨淋巴结活检研究

目的：新辅助化疗（neoadjuvant chemotherapy,NAC）目前已成为局部晚期乳腺癌患者的标准治疗模式。本研究旨在评估乳腺癌患者在NAC后接受内乳区前哨淋巴结活检（internal mammary sentinel lymph node biopsy,IMSLNB）的临床获益。方法：回顾性分析2014年4月—2018年4月山东大学附属山东省肿瘤医院乳腺病中心收治的202例接受NAC的原发性乳腺癌患者的临床资料并进行统计分析,入组患者术前均采用“新型注射技术”注射核素示踪剂。术前哨位淋巴结显像和（或）术中γ探测仪发现内乳区前哨淋巴结（internal mammary sentinel lymph node,IMSLN）显像者行经肋间IMSLNB。根据目前的指南评估NAC后接受IMSLNB的临床获益。结果：入组202例患者,NAC后IMSLN显像率为34.2%(69/202),且与临床肿瘤分期相关（P=0.017）,IMSLN显像患者中,临床淋巴结阴性和临床淋巴结阳性（clinical lymph node-positive,cN⁺）患者分别占11.6% (8/69)和88.4%(61/69)。NAC后IMSLNB的成功率为98.6%（68/69）,IMSLN的检出率为33.7%(68/202),转移率为11.8% (8/68),8例IMSLN转移患者,术后淋巴结分期发生了改变,其中1例患者不伴腋窝淋巴结（axillary lymph node,ALN）转移（pN₀至pN_1b）,2例伴1~3枚ALN转移（pN_1a至pN_1c）,4例伴4~9枚ALN转移（pN_2a至pN_3b）,1例伴≥10枚ALN转移（pN_3a至pN_3b）,术后病理学分期也发生了改变（0期至ⅠB期,ⅡA/ⅢA期至ⅢC期）,这8例IMSLN转移患者术后均接受了内乳区放疗（internal mammary node irradiation,IMNI）。结论：NAC后IMSLN有显像的患者,尤其是cN⁺患者,NAC后应接受IMSLNB,以期获得完整的淋巴结分期。IMSLNB能够进一步完善淋巴结病理完全缓解的定义并指导IMNI。     

Prognostic factors in node-positive operable breast cancer patients receiving adjuvant chemotherapy

Summary A retrospective analysis of prognostic factors in 214 consecutive node-positive (N+) operable breast cancer patients, receiving Melphalan+5-fluorouracil adjuvant chemotherapy between 1980 and 1984 was performed. Median follow-up was 95 months. Actuarial disease-free interval (DFI) and survival (S) were determined according to age, menopausal status, histology, size of primary tumor (T), multifocality, tumor location, hormonal receptor status, number of N+, size of N+, tumor spread in axillary fat, and interval between surgery and onset of adjuvant chemotherapy.On univariate analysis two factors were prognostic for DFI and S: number of N+and T size. A comparison between traditionally classified T1 and T2 patients revealed no signifciant difference, but when the cut-off point was shifted from 2 cm to 3 cm, T size represented a highly significant prognostic factor. In patients with T3 cm 5-year DFI was 54% and 5-year S was 76%, while in patients with T>3 cm the respective values were 23% (p<0.001) and 41% (p<0.001). These significant DFI and S differences persisted after adjustment for number of N+ by bivariate analysis.Multivariate analysis supported the importance of T>3 cm as a strong adverse predictor. Four adverse variables, T>3 cm, number of N+4, multifocality, and tumor spread in axillary fat were used to divide our patients into three subsets with significantly different DFI: Group I, with none of the above factors; Group II, with only one factor present; and Group III, with more than one factor present (5 years DFI 66%, 45%, and 21%, respectively; p<0.001).     

淋巴结转移率评价腋窝淋巴结转移的保乳治疗乳腺癌患者预后的价值

目的 探讨淋巴结转移率(LNR)评价接受保留乳房治疗(BCT)并发生腋窝淋巴结转移的乳腺癌患者的预后是否优于pN分期.方法 回顾性分析1998-2007年间152例接受BCT并发生腋窝淋巴结转移的原发浸润性乳腺癌患者的临床资料,比较LNR和pN分期评价乳腺癌患者无病生存率和总生存率的价值.结果 152例患者中,pN1期114例,pN2期23例,pN3期15例.LNR≤0.20者114例,LNR为0.21～0.65者26例,LNR＞ 0.65者12例.单因素分析显示,淋巴结切检总数、pN分期、LNR、雌激素受体状态、孕激素受体状态、放疗均与患者的无病生存率和总生存率有关(均P ＜0.05);诊断年龄和化疗方案仅与患者的总生存率有关(均P＜0.05).多因素分析显示,LNR为影响患者无病生存率和总生存率的独立因素(均P ＜0.05),而pN分期与患者的无病生存率和总生存率无关(均P ＞0.05).在不同pN分期中,LNR也与患者的预后有关.结论 在评价接受BCT、发生淋巴结转移的乳腺癌患者预后时,LNR作为一个独立的预测指标,更优于pN分期.     

Recurrence after sentinel lymph node biopsy with or without axillary lymph node dissection in patients with breast cancer

BACKGROUND: A regional nodal recurrence is a major concern after a sentinel lymph node biopsy (SLNB) alone in patients with breast cancer. In this study we investigated patterns and risk factors of regional nodal recurrence after SLNB alone. PATIENTS AND METHODS: Between January 1999 and March 2005, a series of 1,704 consecutive breast cancer cases in 1,670 patients (34 bilateral breast cancer cases) with clinically negative nodes or suspicious nodes for metastasis who underwent SLNB at a single institute (Saitama Cancer Center) were studied. All 1,704 cases were classified based upon presence or absence of a metastatic lymph node, treated with or without axillary lymph node dissection (ALND). The site of first recurrence was classified as local, regional node, or distant. The regional node recurrences were subclassified as axillary, interpectoral, infraclavicular, supraclavicular, or parasternal. RESULTS: After a median follow-up period of 34 months (range, 2-83 months), first recurrence occurred in local sites in 32 (1.9%) cases, regional nodes in 26 (1.5%) cases, and distant sites in 61 (3.6%) cases. In 1,062 cases with negative nodes treated without ALND and 459 cases with positive nodes treated with ALND, 11 (1.0%) and 15 (3.3%) recurred in regional nodes, respectively, and 4 (0.4%) and 2 (0.6%) recurred in axillary nodes, respectively. Of 822 cases of invasive breast cancer with negative nodes treated with SLNB alone, 10 (1.4%) recurred in regional nodes, and 4 (0.5%) recurred in axillary nodes. In the 10 patients with regional nodal failure, all of the tumors were negative for estrogen receptor (ER) and/or progesterone receptor (PR) and were nuclear grade (NG) 3. CONCLUSIONS: The axillary recurrence rate was low in patients treated with SLNB alone. Omitting ALND is concluded to be safe after adequate SLNB. Risk factors for regional nodal failure after SLNB alone are negative hormone receptor status and high NG.     

Selection of adjuvant chemotherapy for treatment of node-positive breast cancer

Over the past two decades, several studies have suggested that regimens that contain anthracyclines are more effective than those that do not. A meta-analysis by the 2005 Early Breast Cancer Trialists' Collaborative Group confirmed that about 6 months of anthracycline-based polychemotherapy in the adjuvant setting reduced the yearly death rate from breast cancer by about 38% for women younger than 50 years and by 20% for women aged 50-69 years. Although this meta-analysis found that survival was better with regimens that contain anthracycline than with regimens based on cyclophosphamide, methotrexate, and fluorouracil, the best use of anthracycline-based regimens remains unclear. Adjuvant regimens in use can be categorised into three groups: standard-dose anthracycline; escalated-dose epirubicin; and anthracyclines and taxanes. The duration of treatment and combination of dose and drugs varies between these three categories. We reviewed the three types of regimen to establish which provide a better outcome in terms of safety, efficacy, cost, and convenience to patients. We found that both escalated-dose epirubicin and anthracycline-taxane regimens were most effective in terms of disease-free survival and overall survival. Of the specific anthracycline-based regimens, the docetaxel, doxorubicin, and cyclophosphamide regimen (TAC); the fluorouracil, 100 mg epirubicin, and cyclophosphamide regimen (FEC100); and the cyclophosphamide, epirubicin, and fluorouracil regimen (CEF) produced the greatest proportional decreases in 5-year death rate.     

乳腺癌新辅助化疗后前哨淋巴结活检术的研究进展

新辅助化疗（neoadjuvant chemotherapy,NAC）为乳腺癌患者的临床分期降期带来可能,使不可手术变为可手术,不可保乳变为可保乳。前哨淋巴结活检术（sentinel lymph node biopsy,SLNB）极大降低了早期乳腺癌患者的腋窝淋巴结清扫（axillarylymph node dissection,ALND）率。目前,由于检出率较低而假阴性率较高,NAC后乳腺癌患者能否采用SLNB方法评估腋窝淋巴结状态仍有争议。本文将针对NAC后解决SLNB检出率低和假阴性率高的方法以及处理腋窝淋巴结等方面进行综述。      

乳腺癌新辅助化疗后前哨淋巴结活检临床应用价值的探讨

目的:研究分析乳腺癌患者新辅助化疗(NAC)后前哨淋巴结活检(SLNB)检出率和假阴性率的影响因素,探讨乳腺癌NAC后SLNB的可行性.方法:2004-01-01-2012-06-30初诊于山东省肿瘤医院可手术乳腺癌患者241例,所有患者均接受NAC.分析NAC后SLNB的检出率和假阴性率,并探讨患者临床病理因素与SLNB检出率、假阴性率和准确率的相关性.结果:入组患者SLNB检出率为86.3％(208/241),假阴性率为15.0％(22/147),准确率为89.4％(186/208).单因素分析发现,SLNB检出率与示踪方法呈现明显相关,联合示踪法明显增加前哨淋巴结(SLN)的检出率,P=0.038;NAC前腋淋巴结(ALN)肿大有增加患者假阴性率的趋势,P=0.060,但是其他病理因素与SLNB假阴性率均无明显相关;SLN准确率与NAC前ALN状态明显相关,P=0.032.结论:SLNB可以应用于乳腺癌NAC后的患者;联合示踪法明显提高SLN的检出率;NAC前ALN转移状况影响SLNB的假阴性率和准确率,NAC后SLNB替代腋淋巴结清除术(ALND)可能有一定的风险.     

Prognostic value of lymph node ratio in node-positive breast cancer in Egyptian patients

BackgroundBreast cancer in Egypt is the most common cancer among women and is the leading cause of cancer mortality. Traditionally, axillary lymph node involvement is considered among the most important prognostic factors in breast cancer. Nonetheless, accumulating evidence suggests that axillary lymph node ratio should be considered as an alternative to classical pN classification.Materials and methodsWe performed a retrospective analysis of patients with operable node-positive breast cancer, to investigate the prognostic significance of axillary lymph node ratio.ResultsFive-hundred patients were considered eligible for the analysis. Median follow-up was 35 months (95% CI 32–37 months), the median disease-free survival (DFS) was 49 months (95% CI, 46.4–52.2 months). The classification of patients based on pN staging system failed to prognosticate DFS in the multivariate analysis. Conversely, grade 3 tumors, and the intermediate (>0.20 to ⩽0.65) and high (>0.65) LNR were the only variables that were independently associated with adverse DFS. The overall survival (OS) in this series was 69 months (95% CI 60–77).ConclusionThe analysis of outcome of patients with early breast cancer in Egypt identified the adverse prognostic effects of high tumor grade, ER negativity and intermediate and high LNR on DFS. If the utility of the LNR is validated in other studies, it may replace the use of absolute number of axillary lymph nodes.     

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.