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。     

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意义的前瞻性研究

目的:探讨乳腺癌患者新辅助化疗(NAC)后腋窝前哨淋巴结活检的可行性.方法:采用99Tc硫胶体联合亚甲蓝示踪法对60例NAC后达到临床腋淋巴结阴性的乳腺癌患者和60例临床腋淋巴结阴性的早期乳腺癌患者进行腋窝前哨淋巴结活检术(SLNB),评估SLNB的检出率和准确性,比较两组患者SLNB的检出率和假阴性率,并分析NAC后SLNB检出率和假阴性率与患者及肿瘤特点的关系.结果:60例NAC后患者的前哨淋巴结(SLN)检出率为90%,SLNB的敏感度为90%,特异度为93.33%,准确性为91.67%,假阴性率为10%.其检出率和假阴性率与早期乳腺癌组比较,差异均无统计学意义(P=0.743,P=1.000).NAC组化疗前临床分期T3或N2以上者,腋淋巴结的检出率均显著下降,差异有统计学意义(P=0.030,P=0.000),分期N2以上者假阴性率显著增高,差异有统计学意义,P=0.001.结论:对NAC后达到临床淋巴结阴性的乳腺癌患者,腋窝SLN的检出率和假阴性率与早期乳腺癌SLNB差异无统计学意义,化疗前的TN分期是SLNB检出率和假阴性影响因素.     

Long-term standard sentinel node biopsy after neoadjuvant treatment in breast cancer: a single institution ten-year follow-up

IntroductionIn patients with positive lymph nodes (cN+) prior to neoadjuvant treatment (NAT), which convert to a clinically negative axilla (cN0) after treatment, the use of sentinel node biopsy (SNB) is still debatable, since the false-negative rate (FNR) is significantly high (12.6–14.2%). The objective of this retrospective mono-institutional study, with a long follow-up, aimed to evaluate the outcome in patients undergoing NAT who remained or converted to cN0 and received SNB independent of target axillary dissection (TAD) or the removal of at least 3 sentinel nodes (SNs).MethodsThis study analyzed 688 consecutive cT1-3, cN0/1/2 patients, operated at the European Institute of Oncology, Milan, from 2000 to 2015 who became or remained cN0 after NAT and underwent SNB with a least one SN found. Axillary dissection (AD) was not performed if the SN was negative. Nodal radiotherapy (RT) was not mandatory.ResultsAxillary failure occurred in 1.8% of the initially cN1/2 patients and in 1.5% of the initially cN0 patients. After a median follow-up of 9.2 years (IQR 5.3–12.3), the 5- and 10-year overall survival (OS) were 91.3% (95% CI, 88.8–93.2) and 81.0% (95% CI, 77.2–84.2) in the whole cohort, 92.0% (95% CI, 89.0–94.2) and 81.5% (95% CI, 76.9–85.2) in those initially cN0, 89.8% (95% CI, 85.0–93.2) and 80.1% (95% CI, 72.8–85.7) in those initially cN1/2.ConclusionThe 10-year follow-up confirmed our preliminary data that the use of standard SNB is acceptable in cN1/2 patients who become cN0 after NAT and will not translate into a worse outcome.     

Accuracy of sentinel node biopsy after neoadjuvant chemotherapy in breast cancer patients: A systematic review

BackgroundAs neoadjuvant chemotherapy (NAC) is increasingly used to downstage patients with breast cancer, the timing of the sentinel node (SN) biopsy has become an important issue. This review was conducted to determine the accuracy of SN biopsy following NAC.MethodsWe searched Medline, Embase and Cochrane databases from 1993 to February 2009 for studies on patients with invasive breast cancer who underwent SN biopsy after NAC followed by an axillary lymph node dissection (ALND).ResultsOf 574 eligible studies, 27 were included in this review with a total study population of 2148 patients. The pooled SN identification rate was 90.9% (95% confidence interval (CI) = 88.0–93.1%) and the false-negative rate was 10.5% (95% CI = 8.1–13.6%). Negative predictive value and accuracy after NAC were 89.0% (95% CI = 85.1–92.1%) and 94.4% (95% CI = 92.6–95.8%), respectively. The reported SN success rates were heterogeneous and several variables were reported to be associated with decreased SN accuracy, i.e. initially positive clinical nodal status.ConclusionsThere is a potential role for SN biopsy following NAC which could be considered on an individual basis. However, there is insufficient evidence to recommend this as a standard procedure. Further research with subgroup analysis using variables reported to be associated with decreased SN accuracy is required in order to clearly define its value in the subgroups of breast cancer patients.     

染料法前哨淋巴结活检在乳腺癌手术中的应用价值

目的探讨前哨淋巴结活检（SLNB）在乳腺癌手术中的临床应用价值。方法采用亚甲蓝作为示踪染料对乳腺癌开展SLNB，并且对术中冰冻检查前哨淋巴结（SLN）阴性的病例分组施行部分腋窝淋巴结清扫术（PALND）及常规全腋窝淋巴结清扫（TALND），观察术后并发症、生存率等指标并比较分析。结果SLN检出率97．6％，假阴性率14．3％；接受PALND组术后并发症发生率明显低于传统的TALND组，差异有统计学意义（P〈0．05），而总生存率间的差异无统计学意义（P〉0．05）。结论腋区SLNB能准确反映乳腺癌腋窝淋巴转移状态，为临床缩小乳腺癌手术范围和减少术后并发症提供重要参考价值。     

Axillary sentinel lymph node biopsy after neoadjuvant chemotherapy for carcinoma of the breast

BACKGROUND:

The timing and accuracy of axillary sentinel lymph node biopsy (SLNB) in patients who are receiving neoadjuvant chemotherapy (NACT) for breast cancer are controversial. To examine the accuracy of SLNB after NACT, the authors performed SLNB after chemotherapy on all of patients who received NACT at their institution starting in January 1997.

METHODS:

Seventy‐nine women who underwent NACT between 1997 and 2008 comprised this study and were divided as follows: 4 women had stage I disease, 60 women had stage II disease, and 15 women had stage III disease, including 10 women who had multicentric disease. Thirty‐nine women (49.4%) had clinical evidence of axillary metastasis (N1‐N2) at the time of diagnosis. The regimen, the duration of treatment, and the number of cycles of NACT depended on clinical response. The choice of breast conservation therapy or mastectomy was based on the patient's response to treatment and patient preference. All patients underwent SLNB after NACT.

RESULTS:

Seventy‐three patients underwent breast conservation therapy, and 6 patients underwent mastectomy. Sentinel lymph nodes were identified in 98.7% of patients (in 1 patient, SLNB failed to capture 1 proven axillary metastasis), and 29 patients underwent full axillary lymph node dissection. Fourteen patients (17.7%) had no residual carcinoma (invasive or ductal carcinoma in situ) in their breast, 5 patients (6.3%) had residual ductal carcinoma in situ (only), and 60 patients (75.9%) had residual invasive carcinoma. One false‐negative SLNB was reported in the group of 23 patients who underwent full axillary dissection after a negative SLNB. No patient had a subsequent axillary recurrence.

CONCLUSIONS:

SLNB after NACT was feasible in virtually all patients and accurately selected patients who required complete level I and II axillary dissection. NACT frequently downstaged the axilla, converting patients with N1‐N2 lymph node status to N0 status and also avoiding full axillary dissection in these patients. Cancer 2010. © 2010 American Cancer Society.     

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.     

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

Breast Cancer Research and Treatment -     

乳腺癌新辅助治疗后前哨淋巴结活检术应用的研究进展

腋窝淋巴结清扫术(axillary lymph node dissection,ALND)是新辅助治疗(neoadjuvant treatment,NAT)后腋窝淋巴结标准的处理方式.然而,ALND不能使NAT后腋窝淋巴结病理性完全缓解(pathologic complete response,pCR)的患者获益.现已证实,对于临床诊断腋窝淋巴结阴性(cN0)患者,前哨淋巴结活检术(sentinel lymph node biopsy,SLNB)可对其腋窝淋巴结进行准确评估,使部分患者免于接受ALND.目前多家研究机构着力将SLNB引入NAT后cN0的乳腺癌的治疗中,并在提高其检出率,降低假阴性率等方面获得了长足的进步.本文对近年来SLNB应用于NAT后cN0乳腺癌治疗的相关研究成果及诸多用于提高其准确性的方法进行阐述.     

前哨淋巴结活检术在乳腺癌新辅助化疗中的应用进展

前哨淋巴结活检术（sentinel lymph node biopsy,SLNB）主要用于腋窝淋巴结阴性的早期乳腺癌患者,前哨淋巴结阴性者可免除腋窝淋巴结清扫术。但SLNB在非早期乳腺癌患者新辅助化疗过程中的应用是否具有同样的价值,以及如何保证准确率及假阴性率,目前尚无统一共识。本文就SLNB在乳腺癌患者新辅助化疗应用中的研究进展进行综述。     

乳腺癌前哨淋巴结活检意义的探讨

目的:探讨乳腺癌前哨淋巴结检测方法及临床应用价值。方法:对101例乳腺癌病人,采用99锝标记的大分子右旋糖苷(99mTc-DX)和/或美蓝为示踪剂检测前哨淋巴结,术中先行前哨淋巴结活检(SLNB)冰冻病理检查,然后作乳腺癌改良根治术。结果:联合应用示踪剂组与单用美蓝组比较,检出率为97.6%及86.2%,敏感度为100%及77.8%,假阴性率为0及22.2%(均P<0.05);准确率为100%及79.3%(P<0.01)。比较SLNB术中冰冻与术后病理结果,敏感度93.3%,准确率97.8%,假阴性率6.7%,假阳性率0%。结论:SLNB能准确反映早期乳腺癌腋窝淋巴结状态,术中冰冻病理可快速判断SLN的病理状态,有较高的准确性,对临床外科术式选择有实际指导意义。     

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.     

Favorable outcome with sentinel lymph node biopsy alone after neoadjuvant chemotherapy in clinically node positive breast cancer at diagnosis: Turkish Multicentric NEOSENTI-TURK MF-18-02-study

PurposeFactors affecting local outcome were evaluated in patients with clinically node-positive (cN+) breast cancer at diagnosis, who underwent sentinel lymph node biopsy (SLNB) alone after neoadjuvant chemotherapy (NAC).MethodsBetween 2004 and 2018, 303 cytopathology-proven cN (+) patients in a multicentric registry, who received NAC and underwent SLNB alone were analysed. All patients had regional nodal irradiation.ResultsMedian age was 46 (23–70). Of those, 211 patients had ypN0 disease (69.6%), whereas 92 patients had ypN (+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastases (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 36 months (24–172), one patient (0.3%) with macrometastatic SLN was found to have locoregional recurrence as chest wall and supraclavicular LN metastases at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were 87% and 95%, respectively. Patients with cT3/4 (HR = 2.41, 95% CI; 1.14–5.07), non-luminal molecular pathology (HR = 2.60, 95% CI, 1.16–5.82), and non-pCR in the breast (HR = 2.11, 95% CI, 0.89–5.01) were found to have an increased HR compared to others in 5-year DFS. However, no difference could be found between ypN0 and ypN ITC and micrometastasis (HR = 1.23, 95% CI, 0.44–3.47), whereas there was a slight increase in HR of patients with ypN macrometastasis versus ypN0 (HR = 1.91, 95% CI, 0.63–5.79).ConclusionALND could be avoided in meticulously selected cN (+) patients who underwent SLNB after NAC having breast and/or nodal pCR, cT1-2, or low volume residual nodal disease with luminal pathology, as long as axillary radiotherapy is provided.     

Sentinel lymph node biopsy is accurate after neoadjuvant chemotherapy for breast cancer.

PURPOSE: Sentinel lymph node (SLN) biopsy has proved to be an accurate method for detecting nodal micrometastases in previously untreated patients with early-stage breast cancer. We investigated the accuracy of this technique for patients with more advanced breast cancer after neoadjuvant chemotherapy. PATIENTS AND METHODS: Patients with stage II or III breast cancer who had undergone doxorubicin-based neoadjuvant chemotherapy before breast surgery were eligible. Intraoperative lymphatic mapping was performed with peritumoral injections of blue dye alone or in combination with technetium-labeled sulfur colloid. All patients were offered axillary lymph node dissection. Negative sentinel and axillary nodes were subjected to additional processing with serial step sectioning and immunohistochemical staining with an anticytokeratin antibody to detect micrometastases. RESULTS: Fifty-one patients underwent SLN biopsy after neoadjuvant chemotherapy from 1994 to 1999. The SLN identification rate improved from 64.7% to 94.1%. Twenty-two (51.2%) of the 43 successfully mapped patients had positive SLNs, and in 10 of those 22 patients (45.5%), the SLN was the only positive node. Three patients had false-negative SLN biopsy; that is, the sentinel node was negative, but at least one nonsentinel node contained metastases. Additional processing revealed occult micrometastases in four patients (three in sentinel nodes and one in a nonsentinel node). CONCLUSION: SLN biopsy is accurate after neoadjuvant chemotherapy. The SLN identification improved with experience. False-negative findings occurred at a low rate throughout the series. This technique is a potential way to guide the axillary treatment of patients who are clinically node negative after neoadjuvant chemotherapy.     

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.