乳腺癌前哨淋巴结活检的研究进展

前哨淋巴结活检（SLNB）是本世纪继早期乳腺癌保乳治疗后第二个最重要的进展,前哨淋巴结活检是种多学科结合的新方法,比腋窝淋巴结清扫更能准确的进行腋窝分期,乳腺癌前哨淋巴结活检很快运用到临床实践。适当选择病人,由有经验的多学科团队进行前哨淋巴结活检,其精确度超过95％,前哨淋巴结活检广泛应用在可触及的和不可触及的T1和T2的肿瘤病人。最近研究表明,前哨淋巴结活检技术可应用在多中心多病灶的和新辅助化疗后和局部晚期乳腺癌病人。前哨淋巴结活检的重要因素包括注射技术,病例选择,病理分析和活检精确度等,为此简要综述如下。     

Management of the axilla in patients with breast cancer and positive sentinel lymph node biopsy: An evidence-based update in a European breast center

The surgical approach to the axilla in breast cancer has been a controversial issue for more than three decades. Data from recently published trials have provided practice-changing recommendations in this scenario. However, further controversies have been triggered in the surgical community, resulting in heterogeneous diffusion of these recommendations.The development of clinical guidelines for the management of the axilla in patients with breast cancer is a work in progress. A multidisciplinary team discussion was held at the research hospital Policlinico San Matteo from the Università degli Studi di Pavia with the aim to update recommendations for the management of the axilla in patients with breast cancer. An evidence-based approach is presented.Our multidisciplinary panel determined that axillary dissection after a positive sentinel lymph node biopsy may be avoided in cN0 patients with micro/macrometastasis to ≤2 sentinel nodes, with age ≥40y, lesions ≤3 cm, who have not received neoadjuvant chemotherapy and have planned breast conservation (BCS) with whole breast radiotherapy (WBRT). Cases with gross (>2 mm) ECE in SLNs are evaluated on individual basis for completion ALND, axillary radiotherapy or omission of both. Patients fulfilling the criteria listed above who undergo mastectomy, may also avoid axillary dissection after multidisciplinary discussion of individual cases for consideration of axillary irradiation. Women 70 years or older with hormone receptors positive invasive lesions ≤3 cm, clinically negative nodes, and serious or multiple comorbidities who undergo BCS with WBRT, may forgo axillary staging/surgery (if mastectomy or larger tumor, comorbidities and life expectancy are taken into account).     

乳腺癌新辅助化疗后腋窝及内乳前哨淋巴结活检研究

背景与目的：临床新辅助化疗(neoadjuvant chemotherapy,NAC)后腋窝淋巴结(axillary lymph node,ALN)转阴的患者腋窝前哨淋巴结活检(axillary sentinel lymph node biopsy, ASLNB)能否替代腋窝淋巴结清扫(axillary lymph node dissection,ALND)尚存在争议,且此前研究只评估ALN病理状况而未评估内乳淋巴结(internal mammary lymph node,IMLN)状况。本研究旨在评估NAC后乳腺癌患者接受ASLNB和内乳前哨淋巴结活检(internal mammary sentinel lymph node biopsy,IM-SLNB)的临床意义。方法：回顾性分析2012年1月—2014年12月山东省肿瘤医院乳腺病中心原发性乳腺癌(cT_1-4N_0-3M₀)60例患者的临床资料,将患者分为3组：A组初始cN₀且NAC后为ycN₀,B组初始cN+且NAC后为ycN₀,C组NAC后为ycN₊。术前接受核素注射。术中A组和B组联合亚甲蓝行ASLNB。A组仅对腋窝前哨淋巴结(axillary sentinel lymph node,ASLN)阳性者行ALND;B组行ASLNB后转行ALND;C组直接行ALND。术前淋巴显像和(或)γ探测仪发现内乳前哨淋巴结(internal mammary sentinel lymph node,IM-SLN)的患者行IM-SLNB。结果：A组、B组和C组分别收集6例、45例和9例。A组ASLNB成功率为100%(6/6),仅1例ASLN阳性转行ALND。B组ASLNB成功率为100%(45/45),假阴性率为17.9%(5/28)。其中检出1枚、2枚和＞2枚ASLN的假阴性率分别为27.3%(3/11)、20.0%(2/10)和0%(0/7)。C组所有患者ALN均有转移。IM-SLN总体显像率为63.3%(38/60)。IM-SLNB的总体成功率为97.4%(37/38),转移率为8.1%(3/37),并发症发生率为5.3%(2/38)。结论：对初始cN₀且NAC后为ycN₀者ASLN阴性时ASLNB可替代ALND;对初始cN₊且NAC后为ycN₀者,联合双示踪剂且检出＞2枚ASLN可满足临床可接受的假阴性率(<10%);对NAC后仍为ycN₊者应行ALND。NAC后IM-SLN显像者应行IM-SLNB,以获得完整分期、评估预后并指导术后放疗,有望完善病理完全缓解(pathological complete response,pCR)定义。     

乳腺癌前哨淋巴结活检意义初探

目的：探讨开展乳腺癌前哨淋巴结活检(Sentinel lymph node biopsy，SLNB)的必要性、可行性、准确性及临床应用价值。方法：对45例临床、B超及钼靶检测腋窝LN阴性的原发乳腺癌患者，术中在原发肿瘤周围注射专利蓝进行腋窝淋巴结切除(SLNB)，随后行腋窝淋巴结清扫(ALND)。术中对部分SLN、术后对全部LN行常规病理检查。结果：45例患者中41例检测到SLN，成功率91．1％；假阴性率为6．66％，SLNB总的敏感性是93．3％，特异性是96．1％；总的阳性和阴性预测值分别是93．3％和96．1％。结论：乳腺癌SLNB是一项有实用价值的新技术，目前国内外仍在研究阶段，随着研究的扩大与深入将有可能取代常规的ALND。     

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.     

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.     

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.     

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.     

Axillary recurrence after negative sentinel lymph node biopsy under local anesthesia in breast cancer

The procedure known as sentinel lymph node biopsy (SLNB) under local anesthesia (LA) allows surgical teams to avoid the uncertainties of frozen tissue examination and to perform axillary dissection on patients who have been informed of the risks of lymph node invasion prior to the procedure.     

乳腺癌前哨淋巴结活检研究进展

近年来,乳腺癌的发病率越来越高,乳腺癌治疗方式也在不断改进,但手术仍然是早期乳腺癌治疗的主要手段。对于早期乳腺癌,前哨淋巴结活检术（sentinel lymph node biopsy,SLNB）是一种安全、精确的手术方式,已逐渐替代腋窝淋巴结清扫术（axillary lymph node dissection,ALND）成为早期乳腺癌治疗的标准术式。随着研究的深入,SLNB的应用范围更广,术后生活质量显著改善,但其操作尚需要进一步统一规范。在前哨淋巴结微转移、宏转移、前哨淋巴结活检阳性的老年患者以及新辅助化疗的前哨淋巴结活检等方面尚未达成共识,还需要更多大型多中心前瞻性的随机试验来进一步论证。     

An axilla scoring system to predict non-sentinel lymph node status in breast cancer patients with sentinel lymph node involvement

Background. Axillary lymph node dissection (ALND) is the current standard of care for breast cancer patients with sentinel lymph node (SN) involvement. However, the SN is the only involved axillary node in a significant proportion of these patients. Here we examined factors predictive of non-SN involvement in patients with a metastatic SN, in order to develop a scoring system for predicting non-SN involvement.Materials and Methods. This study was based on a prospective database of 337 patients who underwent SN biopsy for breast cancer, of whom 81 (24) were SN-positive; we examined factors predictive of non SN involvement in the 71 of these 81 women who underwent complementary ALND. All clinical and histological criteria were recorded and analysed according to non-SN status, by using Chi-2 analysis, Students t-test, and multivariate logistic regression.Results. Univariate analysis showed a significant association between non-SN involvement and histological primary tumor size (p=0.0001), SN macrometastasis (p=0.01), the method used to detect SN metastasis (H&E versus immunohistochemistry) (p=0.03), the number of positive SNs (p=0.049), the proportion of involved SNs among all identified SNs (p=0.0001) and lymphovascular invasion (p=0.006). Histological primary tumor size (p=0.006), SN macrometastasis (p=0.02) and the proportion of involved SNs among all identified SNs (p=0.03) remained significantly associated with non-SN status in multivariate analysis. Based on the multivariate analysis, we developed an axilla scoring system (range 0–7) to predict the likelihood of non-SN metastasis in breast cancer patients with SN involvement.Conclusion. In patients with invasive breast cancer and a positive SN, histological primary tumor size, the size of SN metastases, and the proportion of involved SNs among all identified SNs were independently predictive of non-SN involvement.     

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.     

乳腺癌前哨淋巴结活检的安全性

循证医学Ⅰ、Ⅱ级证据支持乳腺癌前哨淋巴结活检（SLNB）的安全性。本文就SLNB对腋窝淋巴结的准确分期、前哨淋巴结阴性患者SLNB替代腋清扫术后腋窝复发率和并发症、SLNB的放射安全性、SLNB新的适应症进行讨论。     

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.     

前哨淋巴结活检指导保留乳房手术患者行选择性腋窝淋巴结清除术的研究

目的研究通过前哨淋巴通道（SLC）行前哨淋巴结活检（SLNB）以指导保留乳房手术（breast—conservingtherapy,BCT）患者行选择性腋窝淋巴结清除术（ALND）的可行性。方法采用非随机对照研究,在BCT患者中采用联合示踪法通过SLC行SLNB。对术中检出的前哨淋巴结（SLN）行细胞印片和冰冻切片检查,根据SLN的术中病理结果行选择性ALND,其中SI。N阳性、行ALND者为A组,SI。N阴性仅行SLNB者为B组。定性资料的比较选用Y。检验,两组均数的比较采用t检验。结果2009年1月至2009年12月采用联合示踪法行SLNB的BCT患者共43例,检出42例,A组28例,B组14例。两组患者的SLC均被显影。每例患者被检出SLN1～3枚,平均1．4枚,共被检出59枚。SLNB检出率为97．7％（42／43）。术后病理检查共检出阳性SI,N29例,其中术中细胞印片、冰冻切片及二者联合病理检测分别检出阳性淋巴结27、27、28例。A组ALND相关并发症发生率明显高于B组（P=0．003）。结论通过SLC行SLNB有助于准确定位SLN,能够指导BCT患者行选择性ALND,降低术后并发症。     

早期子宫内膜癌前哨淋巴结活检和淋巴结微转移的研究进展

子宫内膜癌（endometrial cancer,EC）是妇科常见恶性肿瘤之一,近年来很多研究指出前哨淋巴结活检（sentinel lymph node biopsy,SLNB）和前哨淋巴结（sentinel lymph node,SLN）病理超分期可以明确转移淋巴结位置和判定淋巴结转移与否,并被广泛应用于妇科肿瘤。早期子宫内膜癌淋巴结转移率低,然而淋巴结转移情况是指导术后辅助治疗和预测复发的独立危险因素。SLNB与病理超分期等检测手段结合可发现更多的淋巴结转移类型,尤其对淋巴结微转移具有较好检出效果,为早期子宫内膜癌诊疗提供更多依据。本文将对近年来有关早期子宫内膜癌SLNB技术、影响SLNB准确性相关问题、淋巴结微转移问题三方面进行简述,为促进早期子宫内膜癌精准手术治疗,减少术中风险和术后并发症提供可行性方案。     

乳腺癌前哨淋巴结活检术新型示踪剂的研究进展

随着前哨淋巴结活检术成为临床腋窝淋巴结阴性的早期乳腺癌患者的标准处理模式,关于活检示踪剂的研究成为乳腺癌研究的热点之一。目前,临床上应用较多的示踪剂包括蓝染料、核素及二者的结合,但这两种示踪剂存在的某些不足导致发达国家仅有60%的患者进行前哨淋巴结活检,中国仅占约5%,其他发展中国家更少。近年来,各种新型示踪剂的研究层出不穷,如吲哚菁绿、使用微气泡的对比增强超声和超顺磁性氧化铁颗粒等。该文回顾了这三种物质的特性及作为示踪剂的相关研究,这些新型示踪技术仍处于初级研究阶段,有待于进一步实验以便临床应用。     

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。     

A multicenter validation study of sentinel lymph node biopsy by the Japanese Breast Cancer Society

Several pilot studies have indicated that SLN biopsy can be used to identify axillary lymph node metastases in patients with breast cancer. To confirm this finding, a multicenter study in a variety of practice settings was performed. A total of 674 patients with breast cancer at five institutions were enrolled. The techniques of SLN identification included the vital dye-guided and the vital dye- and gamma probe-guided methods. The SLN was removed, and complete axillary lymph node dissection (ALND) was performed. SLN and ALND specimens were examined separately. The SLN was successfully identified in 214 (94%) of 227 patients using the combined dye- and gamma probe-guided methods. The SLN was identified in 332 (74%) of 447 patients using vital dye-guided method alone. Patient age of at least 51 years, medially located primary tumor, and clinically positive nodes were correlated with failure to identify the SLN. The accuracy of SLN biopsy for the detection of metastatic disease was 96% (522 of 546), and the sensitivity was 90% (203 of 226). Accuracy of 100% was achieved in the patients with tumors less than 1.6cm in diameter. All 23 false negative results occurred with larger primary tumors. SLN biopsy can accurately predict the presence or absence of axillary lymph node metastases, particularly in patients with small (1.5cm) breast cancers.