前哨淋巴结阳性乳腺癌患者非前哨淋巴结转移的影响因素分析

目的 前哨淋巴结活检术(sentinel lymph nodes biopsy,SLNB)已经广泛应用于乳腺癌外科治疗,临床发现部分转移淋巴结仅局限于前哨淋巴结.本研究分析前哨淋巴结(sentinel lymph nodes,SLN)阳性乳腺癌患者非前哨淋巴结(non-sentinel lymph nodes,NSLN)转移的影响因素,从而避免不必要的腋窝淋巴结清除(axillary lymph node dissection,ALND).方法 回顾性分析聊城市人民医院乳腺外科2013-07-1-2015-06-30 SLNB阳性行ALND的77例女性乳腺癌患者临床病理资料,分析NSLN转移的影响因素.结果 在SIN清除个数≥4个的情况下,单因素分析发现阳性SLN≥2个(x2=10.109,P=0.01)以及LuminalB型患者(x2=6.442,P=0.02)发生NSLN转移的风险高.Logistic回归进行多因素分析发现,阳性SLN≥2个是影响NSLN转移的独立危险因素(OR=207.833,95％ CI为1.430～30 201.980,P=0.036).结论 阳性SLN数和分子亚型是影响NSLN转移的危险因素,阳性SLN≥2个是影响NSLN转移的独立危险因素.     

乳腺癌伴1～2枚前哨淋巴结转移腋窝外科处理的研究进展

摘 要：乳腺癌腋窝手术对确立临床分期、辅助治疗选择及预后判断均有重要价值。临床淋巴结阴性的乳腺癌,应用前哨淋巴结活检（SLNB）确定腋窝淋巴结分期已成为标准。对于前哨淋巴结（SLN）阴性的乳腺癌,腋窝淋巴结清扫（ALND）可以避免;而对于SLN阳性的乳腺癌,ALND仍是标准的腋窝处理方式。然而,在SLN阳性患者中进一步行ALND后发现,在仅1～2枚SLN阳性患者中,61.4%～64.5%非前哨淋巴结（nSLN）为阴性。已有大量的临床研究探索了特定条件下的1～2枚SLN阳性患者免除ALND的可行性与安全性。全文就乳腺癌伴1～2枚SLN转移腋窝外科处理的相关研究进行综述。     

早期乳腺癌腋窝前哨淋巴结阳性患者腋窝非前哨淋巴结转移风险预测

目的 分析前哨淋巴结活检(SLNB)1~2个阳性乳腺癌患者中非前哨淋巴结(NSLN)转移的影响因素并构建预测模型。方法 回顾分析2008-2014年中国医学科学院北京协和医学院肿瘤医院未行新辅助化疗前哨淋巴结 1~2个阳性并行腋窝淋巴结清扫的乳腺癌患者的临床病理因素。计数资料组间比较采用χ²检验,多因素分析采用Logistic回归模型。以AUC值和校正曲线对Nomogram预测模型进行评估。结果 共 270例患者纳入研究,87例(32.2%)存在NSLN转移。中位年龄46(21~80)岁,中位SLN送检个数4(1~10)个,中位腋窝淋巴结清扫个数20(10~41)个。单因素分析结果显示病理分级、SLN宏转移、阳性SLN个数和阴性SLN个数是腋窝NSLN转移的影响因素(P=0.001~0.045)。多因素分析结果显示病理分级、阳性SLN个数和阴性SLN个数是NSLN转移的独立影响因素(P=0.000~0.041)。乳腺癌NSLN转移Nomogram预测模型AUC=0.70,当预测患者的NSLN转移率≤15%时,假阴性率仅为10.5%。结论 Nomogram预测模型可作为临床医师进行腋窝处理时的决策参考,对于NSLN转移概率低的患者可以避免行腋窝淋巴结清扫或腋窝放疗。     

不同分子分型1～2枚前哨淋巴结阳性乳腺癌免行腋窝淋巴结清扫的多因素分析

目的探讨不同分子分型1～2枚前哨淋巴结（sentinel lymph nodes,SLNs）阳性乳腺癌免行腋窝淋巴结清扫（axillary lymph node dissection,ALND）的临床病理因素,并为临床精准化提供依据。方法回顾性分析2009年6月至2018年6月274例就诊于内蒙古医科大学附属医院和内蒙古医科大学附属人民医院经病理证实的乳腺癌患者的临床病理资料,采用单因素及Logistic多因素分析筛选1～2枚SLN阳性但非前哨淋巴结（nonsentinel lymph node,NSLN）转移率较低的患者,同时明确其与不同分子分型的关系。结果274例1～2枚SLN阳性乳腺癌患者中,NSLN转移率为36.9%（101/274）。HER-2阳性（HR阳性）患者NSLN转移率最高, 占55.3%（21/38）;三阴性乳腺癌（triple negative breast cancer,TNBC）患者中NSLN转移率最低,占18.5%（5/27）。Luminal B型（HER-2阴性）乳腺癌患者的NSLN转移率明显高于Luminal A型（P=0.010）和TNBC患者（P=0.011）;HER-2阳性（HR阳性）乳腺癌患者的NSLN转移率明显高于Luminal A型（P=0.002）和TNBC患者（P=0.003）。 Logistic多因素分析显示,SLN转移数目（OR=4.022, 95%CI为2.348～6.889,P<0.001）,SLN检测（OR=3.846, 95%CI为1.541～9.600,P=0.004）,组织学分级（P<0.001）和分子分型（P=0.004）是1～2枚SLN阳性乳腺癌NSLN转移的独立影响因素。结论Luminal B型（HER-2阴性）和HER-2阳性（HR阳性）患者的NSLN阳性率较高,SLN转移数目、SLN检测、组织学分级和分子分型是NSLN转移的独立影响因素。      

女性乳腺癌患者前哨淋巴结和非前哨淋巴结转移危险因素研究

目的 分析前哨淋巴结(SLN)与非前哨淋巴结(NSLN)转移的危险因素,从而避免过度的腋窝淋巴清除治疗.方法 收集2015-09-01-2020-04-25新疆石河子大学医学院第一附属医院收治的422例患乳腺癌并行前哨淋巴结活检术(SLNB)患者的相关临床资料,部分SLN阳性患者行腋窝淋巴结清除术(ALND).采用病例...     

ACOSOG Z0011试验标准用于中国前哨淋巴结阳性乳腺癌患者以避免腋窝淋巴结清扫的可行性研究

背景与目的:美国外科医师学会肿瘤学组(American College of Surgeons Oncology Group,ACOSOG)Z0011试验的结果改变了乳腺癌前哨淋巴结(sentinel lymph node,SLN)阳性患者的传统治疗模式。本研究的目的在于探讨ACOSOG Z0011试验标准用于中国前哨淋巴结阳性乳腺癌患者以避免腋窝淋巴结清扫(axillary lymph node dissection,ALND)的可行性。方法:连续收集194例SLN阳性的乳腺癌患者,根据Z0011的标准分为可以只做前哨淋巴结活检(sentinel lymph node biopsy,SLNB)组和仍需做ALND组。将SLNB组患者的临床病理学特征与Z0011试验标准的原始入组人群进行比较,再将SLNB组与ALND组患者的临床病理学特征进行比较。结果:194例患者中有77例符合Z0011标准可以只做SLNB,117例患者不符合Z0011标准,需要做ALND;SLNB组患者与Z0011标准原始入组人群比较,T1期肿瘤、ER阳性肿瘤、淋巴结转移数目少的肿瘤、非前哨淋巴结(non-sentinel lymph node,NSLN)阴性的肿瘤都显著多于Z0011标准原始人群,差异有统计学意义(P<0.05)。本研究ALND组患者与SLNB组患者比较,T2、T3期肿瘤较多,但差异无统计学意义(P>0.05)。ALND组腋窝淋巴结转移数目多的患者比例要明显多于SLNB组,NSLN阳性患者比例也高于SLNB组,差异均有统计学意义(P<0.05)。结论:将Z0011试验标准用于SLN阳性乳腺癌患者,能够筛选出较Z0011标准研究中预后更好、更为低危的患者,使得该部分患者可以更为安全的只接受SLNB。     

1枚前哨淋巴结阳性早期乳腺癌保腋窝的可行性分析

目的探讨1枚前哨淋巴结（sentinel lymph node,SLN）阳性的早期乳腺癌患者保腋窝（omitting axillary dissection,OAD）的可行性。方法用美蓝作为示踪剂先行乳腺癌前哨淋巴结活检术（sentinel lymph node biopsy,SLNB）,根据快速冰冻病理结果分为SLN阴性组与1枚SLN阳性组,随后两组均行常规腋窝淋巴结清扫（axillary lymph node dissection,ALND）以解剖出非前哨淋巴结（non—sentinellymphnode,NSLN）,比较两组间NSLN的阳性率。结果SLN阴性组30例,1例NSLN阳性,阳性率为3．3％,准确性为96．7％（29／30）;1枚SLN阳性组30例,仅3例NSLN阳性,阳性率为10．0％;两组阳性率差异无统计学意义（X^2=1．071,P=0．612）。全组随访1～48个月,均无区域淋巴结复发。结论1枚SLN阳性的早期乳腺癌患者可考虑OAD。     

前哨淋巴结活检指导乳腺癌腋窝淋巴结清扫的研究进展

腋窝淋巴结清扫（axillary lymph node dissection,ALND）对降低乳腺癌患者的复发转移率、延长乳腺癌患者生存期具有重要意义,临床上绝大部分前哨淋巴结活检（sentinel lymph node biopsy,SLNB）结果阳性的乳腺癌患者均接受ALND。但现有研究显示,部分前哨淋巴结阳性的乳腺癌患者并没有因ALND而取得生存获益,这就引发了对于SLNB阳性的乳腺癌患者是否必须行ALND问题的思考。本文就近年来SLNB指导乳腺癌患者ALND相关研究的新进展进行综述。     

前哨淋巴结活检术在早期乳腺癌保腋窝治疗中的应用

目的：探讨乳腺癌前哨淋巴结活检术（sentonel lymph node biopsy,SLNB）对SLN阴性者进行保腋窝的可行性。方法：联合应用专利蓝（patent blue-v）和^99mTc标记的硫胶体（^99mTc-Sulphur colloid,^99mTc-Sc）行乳腺癌前哨淋巴结活检术。对SLN阴性并同意保腋窝者免除腋窝淋巴结清扫（axillary lymph node dissection,ALND）,对SLN阳性或虽SLN阴性但不同意保腋窝者仍行ALND。结果：2002年3月～2006年3月入组临床分期T1～2N0M0乳腺癌患者135例,均行SLNB。SLN阳性44例,其中42例行ALND,2例镜下有微小转移灶者仅行SLNB术后加腋窝淋巴结区域放疗;SLN阴性91例（67.4%）,其中的39例仅行SLNB,52例仍行ALND。全组SLNB准确率97.8%（132/135）,假阴性率6.8%（3/44）。全组中位随访43个月（24～72个月）,SLNB保腋窝者术后并发症明显低于ALND者（P〈0.05）,区域淋巴结无复发,ALND者区域淋巴结亦无复发。结论：SLNB保腋窝近期疗效满意具有良好的微创效果。     

乳腺癌SLN阳性与残余腋淋巴结阳性的预测因素

目的明确前哨淋巴结(SLN)阳性乳腺癌中不同的临床病理特点,并确定非SLN(NSLN)发生转移的预测因素。方法回顾分析726例成功确定了SLN的0~Ⅱ期乳腺癌病例,SLN阳性的185例患者接受腋窝淋巴结清除(ALND)。根据NSLN有无转移,将该185例分为两组,残余腋窝淋巴结有转移组(NSLN )81例,残余腋窝淋巴结无转移组(NSLN-)104例。结果多变量分析显示,原发肿瘤较大(>2.0cm)、淋巴管浸润、阳性SLN较大(>2mm)、所获得的SLN全部阳性4项均与NSLN阳性相关。在4项因素均存在的病例中,73%(30/41)存在NSLN阳性。结论4项独立的预测因素与NSLN转移有关。     

Impact of CD44+CD24- cells on non-sentinel axillary lymph node metastases in sentinel node-positive breast cancer

Although complete axillary lymph node dissection (ALND) is the standard for evaluating axillary status after the identification of a positive sentinel lymph node (SLN) in breast cancer; approximately 40-60% of SLN-positive patients have negative non-SLN. In this study, to explore putative breast cancer stem cells with CD44+CD24- in the SLN, we retrospectively analyzed the expression of CD44+CD24- on metastatic tumor cells within SLNs as a predictive factor for positive non-SLNs (NSLNs). We tested 271 patients for SLNs using serial sectioning with cytokeratin immunohistochemistry (IHC) and hematoxylin-eosin staining and identified 67 patients who had a positive SLN biopsy and complete ALND. CD44 and CD24 expression was detected using double-staining IHC. Twenty-eight (41.8%) out of 67 patients had positive NSLN metastases. Seven positive SLNs with micrometastases were not available for the evaluation of CD24 and CD44 expression. Out of the remaining 60?patients, 19?(31.7%), 44?(73.83%) and 37?(61.7%) patients had CD24+, CD44+ and CD44+CD24- metastatic tumor cells in SLNs, respectively. Positive NSLN metastasis was significantly associated with the primary tumor size (P=0.004), CD24- expression (P=0.04), CD44+ expression (P=0.01) and CD44+CD24- expression (P=0.02). This report provides the first evidence of the existence of a putative stem-like phenotype within the SLN, which is significantly associated with positive NSLN in early breast cancer patients.     

Clinicopathological parameters and biological markers predicting non-sentinel node metastasis in sentinel node-positive breast cancer patients

The value of complete axillary lymph node dissection (ALND) has been questioned in invasive breast cancer (IBC) patients with positive sentinel lymph nodes (SLNs) who have no non-sentinel lymph node (NSLN) metastases. Because biological markers have not been systematically studied in this setting, we sought to identify clinicopathological characteristics and biological markers for predicting NSLN metastases in SLN-positive IBC patients. Two hundred and five IBC patients who had at least one positive SLN and received SLN biopsy and ALND were included in our study. We examined the clinicopathological characteristics of their primary tumors, SLNs and NSLNs. We also evaluated the biological markers of the primary tumors by tissue microarray and immunohistochemistry. Of the 205 patients with SLN metastases, 89 patients (43.4%) had additional metastases in NSLNs. The following factors were found to be associated with NSLN metastases: peritumoral lymphovascular invasion (p=0.01), two or more metastatic SLNs (p<0.01), SLN metastasis >2.0 mm (p<0.01) and extra-nodal extension (p<0.01). Primary tumors >2.0 cm showed more NSLN metastases, but the association was statistically insignificant (p=0.08). In contrast, NSLN metastases were not associated with histologic grade, histologic type, presence of extensive intraductal component, presence of high grade ductal carcinoma in situ and number of harvested SLNs. Biological markers such as E-cadherin, CD44, cyclin D1, p21, ER, PR, c-erbB2, p53, Ki-67, luminal (CK7, CK18, CK19) and basal (CK5, p63) markers were not useful predictors of NSLN metastasis in IBC patients with SLN metastases. Multivariate analysis revealed that SLN metastasis >2.0 mm (p=0.01), two or more metastatic SLNs (p=0.03) and extranodal extension (p<0.01) were independent predictors of NSLN metastasis. For the prediction of NSLN metastasis in IBC patients with SLN metastases, light microscopic evaluation of the number, size and extranodal extension of metastatic SLNs by hematoxylin and eosin staining appeared to be critical. However, the biological markers of primary tumor characterized by immunohistochemical staining, such as luminal and basal markers, hormone receptors, E-cadherin, CD44, cyclin D1, p21, c-erb-B2, p53 and Ki-67, did not appear to be helpful predictors.     

Sentinel lymphadenectomy without systematic axillary dissection in breast cancer patients: predictors of non-sentinel lymph node metastasis.

AIMS: To identify factors predicting metastatic involvement of non sentinel axillary lymph nodes in breast cancer patients who underwent sentinel lymph node (SLN) biopsy followed by complete axillary dissection only in case of metastatic sentinel lymph node. METHODS: A prospective database including 165 breast cancer patients who underwent SLN biopsy without further complete axillary dissection in case of non-metastatic SLN was reviewed. Primary tumor size, pathologic grade, lymphatic invasion in the primary tumor, estrogen receptor status, tumor size in the SLN and number of metastatic SLNs were tested as possible predictors of metastatic involvement of non-SLN. RESULTS: The sentinel lymph node detection rate was 97% (160/165 patients). The mean number of SLNs per patient was 1.8 (range: 1-5). Fifty patients (31.3%) had a metastatic axillary SLN: 10 of the 42 patients with T1a or T1b breast tumors and 40 of the 118 patients with T1c< or = 15mm tumors. Fifteen of the 50 patients with metastatic SLN had metastatic non-SLN. Primary tumor size, tumor size in the SLN, pathologic grade, estrogen receptor status and age were not significantly associated with metastatic involvement of non-SLN. Number of metastatic SLNs fell short of reaching statistical significance (P: NS). Lymphatic invasion in the primary tumor was the only factor significantly associated with the presence of tumor in the non SLN (P<0.01). CONCLUSION: In our series, only lymphatic invasion in the primary tumor was correlated with metastases detection in the non-SLN. We could not identify a subset of patients without metastatic non-SLN in patients with metastatic SLN.     

Predictors of tumour involvement in remaining axillary lymph nodes of breast cancer patients with positive sentinel lymph node.

AIMS: To characterize the various clinicopathologic features in cases of breast cancer with positive sentinel lymph nodes (SLNs), in order to determine factors that might help in predicting the involvement of the non-SLNs. METHODS: A retrospective database review was performed of 726 breast cancer patients with stage 0-II, in whom SLNs were successfully identified. One hundred eighty-five of these patients showed positive SLNs, and subsequently underwent axillary lymph node dissection (ALND). These cases were divided into two groups based on the presence or absence of metastases in the non-SLNs, i.e. positive non-SLNs (NSLN+; 81 cases) and negative non-SLNs (NSLN-; 104 cases). RESULTS: Multivariate analysis revealed that a larger size of the primary tumour (>2.0cm), presence of lymphatic invasion, larger size of the largest SLN metastasis (>2mm), and a 100% metastatic rate in the SLNs (number of positive SLNs/number of harvested SLNs) were significantly associated with NSLN+. Among the cases in which all the four factors were present, 73% (30/41) were found to have NSLN+. CONCLUSION: We found four independent predictors in relation to non-SLN metastasis. Although these factors might be useful for determining the need of additional ALND, it would seem that even the presence of all of these four factors in combination may be insufficient to safely omit ALND. Thus, until further evidence is accumulated from the results of large clinical trials, ALND would still be recommended for patients with SLN metastasis.     

乳腺癌前哨淋巴结临床病理的研究

目的：探讨乳腺癌前哨淋巴结能否准确反映腋窝淋巴结转移情况,方法对36例例早期乳腺癌,常规HE染色检测腋窝淋巴结,对HE染色阴性的前哨淋巴结及所属非前啉巴结,连续切片、免疫组化染色,检测其肿瘤的转移情况,结果常规病理检测36例中,10例腋窝有转移,其中2例仅哨淋巴结有肿瘤转移,连续切片,组化检测26例阴性的前哨淋巴结共61例,非前哨淋巴结406枚,2例（2枚）仅前哨淋巴结发现有肿瘤转移,余245例前哨淋巴结及非前哨淋巴结无肿瘤转移,HE染色的检测阴性的前哨淋巴结患者假阴性率为7．7％（2／26）。结论早期腺癌前哨淋巴结可以准确反映腋窝巴结转移情况。     

美蓝在乳腺癌前哨淋巴结活检中的临床价值

目的探讨美蓝在乳腺癌前哨淋巴结活检中的临床价值。方法将1%美蓝2ml注入活检腔外上方的皮下及乳腺组织内,然后行Auchincloss仿根治术,依淋巴管走向找到蓝染淋巴结定为SLN,若此时未找到待腋窝清扫结束后,再在标本中寻找,蓝染者为SLN,余为非SLN,分别送病理检查。结果前哨淋巴结检出率为87.9%(95/108),SLN预测腋窝状况的准确率为95.7%(91/95),假阴性率为6.5%(4/62),无假阳性者。未检出者13例,其中4例为假阴性,均属跳跃式转移。前哨淋巴结转移阳性率(34.6%,33/95)和阴性率(65.3%,62/95),与全腋淋巴结转移阳性率(39.8%,43/108)和阴性率(60.2%,65/108)比较,均无显著性差异(P>0.05)。结论美蓝前哨淋巴结活检可以准确预测乳腺癌患者的腋淋巴结状态。     

Sentinel lymph node biopsy alone without axillary lymph node dissection--follow up of sentinel lymph node negative breast cancer patients.

AIMS: To evaluate the rate of axillary recurrences in sentinel lymph node (SLN) negative breast cancer patients after sentinel lymph node biopsy (SLNB) alone without further axillary lymph node dissection (ALND). METHODS: Between May 1999 and February 2001 all patients who had primary invasive breast cancer and were SLN negative were eligible for this prospective study. SLNB was performed by using the combined method with radioactive tracer and blue dye. SLNs were examined by frozen section, standard H/E staining and immunohistochemistry staining. SLN negative patients did not receive further ALND. Follow-up was done three-monthly with clinical controls, blood samples and ultrasound of the breast and axilla. An annual mammogram was performed. RESULTS: 116 patients with T1 or T2 invasive breast cancer were included in this trial. All 116 patients had negative SLNs in frozen sections, in H/E staining and in immunohistochemistry staining. The mean number of removed SLNs was 2.03+/-1.22. Mean tumor size was 17.15+/-7.62 mm. Postmenopausal patients totalled 79.3 and 20.7% of patients were premenopausal. No local or axillary recurrences occurred at a mean duration of follow-up of 22.12+/-6.38 months. CONCLUSION: The absence of axillary recurrences after SLNB without ALND in SLN negative breast cancer patients supports the hypothesis that SLNB is accurate and safe while providing less surgical morbidity. Short term results are very promising. SLNB without ALND in SLN negative patients is an excellent procedure for axillary staging in a cohort of breast cancer patients with small tumors.     

Predictors of non-sentinel lymph node metastasis in breast cancer patients

In many patients, the sentinel lymph node (SLN) is the sole site of regional nodal metastasis. This subgroup of patients would not be expected to benefit from completion axillary lymph node dissection (CALND). This study evaluated the factors that may determine the likelihood of additional positive nodes in the axilla in the presence of sentinel node metastasis. A total of 618 breast cancer patients underwent SLN biopsy based on lymphoscintigraphy, intraoperative gamma probe detection, and blue dye mapping using 99mTc-nanocolloid and Patent Blue V injected peritumourally. This was followed by standard axillary node clearance at the same operation. Of the 201 patients with a positive SLN, 105 (52%) patients had no further positive nodes in the axilla, 96 (48%) patients had additional metastasis in non-sentinel lymph nodes (NSLN) upon CALND. In patients with a positive SLN, increasing tumour size and tumour grade significantly increased the frequency of additional positive nodes on univariate analysis. The number of SLNs removed and the number of negative SLNs were significant negative predictors. Increasing tumour burden in the sentinel nodes (determined by the number of positive SLNs) was significantly associated with increasing likelihood of positive NSLNs. Multivariate analysis revealed that the rest of the axilla is more likely to be positive if there are more positive than negative SLNs removed and more likely to be negative otherwise. A group of cases from one centre (Cardiff) were subjected to further detailed analysis. Tumour burden in the positive SLN was assessed by measuring the size of metastasis, percentage replacement of the SLN by tumour and by documenting extracapsular extension (ECE) around the SLN. Of the 64 patients with a positive SLN, 34 (53%) patients had no further positive nodes in the axilla, 30 patients (47%) had additional metastasis in NSLNs upon CALND. Increasing tumour burden in the SLN was associated with additional positive nodes in the axilla. Multivariate analysis revealed that size of the SLN metastasis is the most important predictor of involvement of only the SLN. Overall, in patients with a positive SLN, the difference in the number of positive and negative SLNs removed and size of the metastasis in the SLN, all predicted the frequency of additional positive nodes.