前哨淋巴结时代乳腺癌的精准区域处理：演进与展望

区域淋巴结状况是乳腺癌重要的预后指标之一,可以指导分期和辅助治疗策略的制定。近30年来乳腺癌前哨淋巴结活检术（sentinel lymph node biopsy,SLNB）研究发展迅速,循证医学Ⅰ类证据支持其为临床腋窝淋巴结阴性早期乳腺癌患者安全、有效的腋窝分期技术,前哨淋巴结阴性及低肿瘤负荷患者SLNB替代腋窝淋巴结清扫术后腋窝复发风险和并发症极低。乳腺癌局部区域控制新理念——应该综合考虑远处转移风险、全身治疗效果与不良反应以及局部区域治疗（手术/放疗）效果与不良反应——推动了SLNB适应人群不断扩展,新辅助治疗与SLNB、内乳SLNB将进一步促进区域淋巴结处理降阶梯,豁免腋窝手术临床研究值得期待。SLNB标志着乳腺癌区域淋巴结迈入微创化精准诊疗时代。本文就前哨淋巴结时代乳腺癌的精准区域处理的演进过程和最新进展进行总结,以期为广大临床工作者提供参考。     

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。     

前哨淋巴结微转移与腋窝淋巴结复发关系的研究进展

乳腺癌是女性最常见的恶性肿瘤，而腋窝淋巴结的转移状态与乳腺癌患者的预后相关。自从开展乳腺癌前哨淋巴结活组织检查以来，一部分乳腺癌患者因前哨淋巴结阴性而免除了腋窝淋巴结清扫，而另一部分患者因前哨淋巴结微转移选择术后放射治疗或是化疗以替代腋窝淋巴结清扫，从而减少了患侧上肢淋巴水肿、运动障碍以及感觉障碍等并发症的发生。近年来，少部分前哨淋巴结微转移患者发生了不同程度的腋窝淋巴结复发。对此，部分学者认为前哨淋巴结微转移患者即使不做腋窝淋巴结清扫，腋窝淋巴结复发率也未见明显增加；但部分学者则认为前哨淋巴结微转移应被视为腋窝淋巴结转移，残留的肿瘤病灶能增加腋窝淋巴结复发率，因此应行腋窝淋巴结清扫术。对于前哨淋巴结微转移的处理方式，国内外专家尚未得出一致的结论。目前众多研究者仍在不懈地进行相关临床试验及大数据分析，旨在为前哨淋巴结微转移患者寻求更佳的治疗方案。     

乳腺癌前哨淋巴结活检假阴性原因研究新进展

乳腺癌根治术常规进行腋窝淋巴结清扫术,往往给患者造成疼痛、水肿、运动和感觉功能障碍。前哨淋巴结活检(sentinel lymph node biopsy,SLNB)是一种微创的淋巴结活检方法,用前哨淋巴结评估整个腋窝淋巴结转移情况,有针对性的指导清扫腋窝淋巴结,减小清扫范围,减轻患者腋窝淋巴结清扫后遗症,但是前哨淋巴结活检存在一定比例的假阴性结果,影响其在临床的推广,主要原因有:适应证的选择不当、术前化疗影响、对内乳前哨淋巴结忽略、分子病理学方法利用不充分、单用示踪剂等。增强临床医生和病理医生对乳腺癌前哨淋巴结活检的临床指导作用以及腋窝淋巴结和内乳淋巴结解剖变异的认识,加强SLNB规范操作,借助术中冰冻切片,联合免疫组化,RT-PCR等方法,可降低SLNB假阴性率。     

乳腺癌超声特征与腋窝淋巴结转移相关性的研究进展

腋窝淋巴结状态影响着乳腺癌患者的治疗与预后,因此腋窝淋巴结的术前评估尤为重要。近年来许多研究发现,乳腺癌的常规超声、弹性成像及超声造影特征能够间接反映腋窝淋巴结的转移情况,可用于术前早期评估,避免不必要的前哨淋巴结活检。本文就乳腺癌超声特征与腋窝淋巴结转移间的相关性进行综述。     

乳腺癌新辅助化疗后腋窝淋巴结状态的评估方法研究进展

随着新辅助化疗(neoadjuvant chemotherapy, NAC)在乳腺癌中的应用越来越广泛,部分患者在NAC后实现了乳房保留,同时腋窝淋巴结对NAC反应较好的患者也可能实现腋窝保留。NAC后腋窝淋巴结状态的确定不仅可使患者免于额外的手术,而且能评估腋窝病理完全缓解(pathologic complete response, pCR),这日益成为后续治疗决策的重要参考依据。目前前哨淋巴结活检(sentinel lymph node biopsy, SLNB)在腋窝淋巴结阳性患者NAC后腋窝处理中的应用仍有争议,但已经出现了一些新的方法改善外科技术以保证在肿瘤学上的安全性。这篇综述对近年来NAC后腋窝状态评估方法的相关研究进行梳理和总结,希望为临床上NAC后腋窝的处理提供参考信息。     

前哨淋巴结活组织检查指导乳腺癌腋窝淋巴结清扫问题的思考

乳腺癌是危及女性生命健康最常见的恶性肿瘤之一。近年来,发展中国家乳腺癌的发病率居高不下,中国乳腺癌发病率每年增长约3%,其中京、津、沪等经济发达地区,乳腺癌已跃居女性恶性肿瘤之首[1]。准确的临床分期尤其是腋窝转移淋巴结分级对评估患者预后和制定治疗方案具有重要参考价值,研究发现有腋窝淋巴结侵犯的乳腺癌患者5年无瘤生存率相对于无腋窝淋巴结转移患者下降40%[2]。以前临床上评价腋窝淋巴结转移情况主要依靠腋窝淋巴结清扫（ axillary lymph node dissection, ALND）,致使绝大多数乳腺癌患者均接受了腋窝淋巴结清扫。自从20世纪90年代前哨淋巴结活组织检查（ sentinel lymph node biopsy, SLNB）首次应用于乳腺癌手术以来, SLNB逐渐改变了上述状况,使得SLNB阴性的乳腺癌患者避免接受ALND,SLNB现已成为决定患者是否需要进行ALND的主要依据[3]。近年来,临床研究结果提示部分SLNB阳性的乳腺癌患者即使不接受 ALND,其预后也不会因此受到影响[4],这引起了学者对SLNB 阳性乳腺癌患者是否一定要行ALND问题的思考。笔者就近年来有关SLNB指导腋窝淋巴结切除的研究成果进行总结,并展望SLNB在未来临床实践过程中的指导作用。     

1个前哨淋巴结阳性乳腺癌患者的腋窝非前哨#br# 淋巴结转移情况及危险因素分析#br#

目的研究1个前哨淋巴结阳性的乳腺癌患者腋窝非前哨淋巴结（NSLN）转移情况及危险因素,为该类患者豁免腋窝淋巴结清扫（ALND）提供指导。方法选取2013年1月至2020年12月在哈尔滨医科大学附属肿瘤医院行前哨淋巴结活检（SLNB）证实仅有1个前哨淋巴结阳性且行ALND的乳腺癌患者465例,根据其腋窝NSLN转移情况,分为NSLN转移组104例,NSLN未转移组361例。比较两组的一般资料,采用二元Logistic回归分析腋窝NSLN转移的独立影响因素。结果465例仅1个前哨淋巴结转移的乳腺癌患者中,104例（224%）发生腋窝NSLN转移。其中,多个亚组患者的腋窝NSLN转移率<10%,如肿瘤T1a+b期的NSLN转移率仅91%、肿瘤T1期且前哨淋巴结数量＞5个的腋窝NSLN转移率仅70%等。单因素分析结果显示,NSLN转移组与NSLN未转移组前哨淋巴结数、肿瘤T分期差异有统计学意义（P<005）。前哨淋巴结2～5个、肿瘤分期为T2～T3期的患者更容易发生腋窝NSLN转移。多因素Logistic回归分析显示,肿瘤分期为T2～T3期、前哨淋巴结数≤5个是患者腋窝NSLN转移的独立危险因素。结论仅有1个前哨淋巴结转移的乳腺癌患者总体腋窝NSLN转移率为224%,肿瘤T分期和前哨淋巴结数为腋窝NSLN转移的影响因素,在对仅1个前哨淋巴结阳性的乳腺癌患者豁免ALND时应重点考虑。     

PET/CT对cT1-2N0M0期乳腺癌腋窝淋巴结转移的诊断价值

目的探讨PET/CT检查对cT1-2N0M0期乳腺癌腋窝淋巴结转移情况的诊断价值。方法 40例cT1-2N0M0乳腺癌患者,在PET检查医师和患者双盲的情况下行PET/CT检查,以术后病理检查结果为金标准,对PET检查的漏诊率、误诊率、灵敏度、特异度等指标进行分析。结果 40例乳腺癌患者腋窝淋巴结转移误诊率为18.18%,漏诊率为27.78%,灵敏度为78.26%,特异度为76.47%;PET/CT对腋窝淋巴结定性诊断的灵敏度和特异性优于单纯CT检查（P〈0.05）。结论 PET/CT检查对乳腺癌腋窝淋巴结转移定性诊断的误诊率低,特异性较好;可为术式选择和腋窝淋巴结清扫术的取舍提供参考。对于不愿接受腋窝前哨淋巴结活检的患者,先行PET/CT检查是比较理想的选择。     

乳腺癌前哨淋巴结的研究热点与评价

前哨淋巴结活检已成为早期乳腺癌区域淋巴结评估的标准术式。随着乳腺癌精准诊疗和预后判断的需要,临床上仍有一些问题值得深入探讨,包括新型示踪剂的临床应用、内乳前哨淋巴结活检在乳腺癌预后判断中的价值、淋巴结阳性患者新辅助治疗后豁免腋窝淋巴结清扫的安全性等。从以上几方面的问题出发,引用近期国内外相关研究结果,就这些乳腺癌前哨淋巴结的研究热点进行分析并展开讨论,以推动早期乳腺癌外科诊疗的规范化。     

Clinical and pathologic factors predicting axillary lymph node involvement in breast cancer

The diagnosis of axillary disease remains a challenge in the management of breast cancer and is a subject of controversy. In 1998, the Japanese Breast Cancer Society conducted a study assessing axillary lymph node involvement in breast cancer. The study included (a) clinical assessment by pre-operative imaging modalities, (b) histologic assessment for peritumoral lymphatic invasion, (c) biologic assessment by gelatinolytic activity using film in situ zymography, and (d) sentinel lymph node (SLN) biopsy. Clinical assessments by CT, PET, and US as well as biologic assessment were limited in their ability to detect axillary lymph node disease, although these imaging techniques may be useful to exclude node-positive patients from the need for SLN biopsy. Histologic assessment for peritumoral lymphatic invasion was useful, particularly for detecting false-negative cases by SLN biopsy. Nevertheless, the utility of SLN biopsy in assessing axillary nodal status was confirmed. Axillary lymph node dissection (ALND) can be avoided in patients with a small tumor and a negative SLN. However, further studies will be required to investigate the value of SLN biopsy for predicting regional control and survival before it can replace routine ALND as the optimal staging procedure for operable breast cancer.     

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.     

乳腺癌腋窝淋巴结声像图联合免疫组织化学与淋巴结转移的相关性研究

背景与目的：乳腺癌腋窝淋巴结转移对于乳腺癌患者的预后及治疗方案的选择有重要的指导意义。本研究旨在探讨乳腺癌腋窝淋巴结声像图表现联合免疫组织化学与腋窝淋巴结转移的相关性。方法：回顾性分析应用超声检出的366例乳腺癌患者共计728枚腋窝淋巴结的声像图表现,采用单因素分析、多因素logistic回归及受试者工作特征(receiver operating characteristic,ROC)曲线分析的方法,分别检验乳腺癌腋窝淋巴结皮质最大厚度、长短径之比、皮髓质之比和淋巴结血流特征,联合乳腺癌术后免疫组织化学结果,研究其与病理学腋窝淋巴结转移的相关性。结果：依据单因素分析,腋窝淋巴结皮质最大厚度、长短径之比、血流特征以及乳腺癌病灶p53的阳性表达率与淋巴结转移有关(P<0.05)。依据多因素分析及ROC分析,腋窝淋巴结皮质最大厚度是判定腋窝淋巴结转移的最佳指标。腋窝淋巴结皮质最大厚度大于3 mm的患者,其乳腺癌病灶的p53阳性表达率(42.78%)明显高于皮质最大厚度小于等于3 mm的患者(25.82%),差异有统计学意义(P<0.01)。结论：乳腺癌腋窝淋巴结声像图表现联合免疫组织化学评价腋窝淋巴结转移,对乳腺癌的临床诊疗方法选择具有重要价值。     

Current applications and future prospects of fine‐needle aspiration biopsy of locoregional lymph nodes in the management of breast cancer

Staging of disease is routine in the evaluation of patients newly diagnosed with breast cancer. Assessment of palpable and/or nonpalpable locoregional lymph nodes is an important component of the initial staging. Ultrasound (US) is the favored imaging modality for the initial investigation of lymph nodes and results in a significant increase in the specificity of the overall evaluation when used in conjunction with fine‐needle aspiration (FNA). This review provides a concise summary, based on published literature, of the current applications and future prospects of FNA biopsy of locoregional lymph nodes in the initial staging and subsequent surgical management of patients with breast cancer. Patients undergo either sentinel lymph node (SLN) biopsy or complete axillary lymph node dissection, based on whether the axillary lymph node status is determined to be negative or positive in the initial staging process. The status of lymph nodes in the supraclavicular, infraclavicular, and internal mammary regions provides more accurate staging information and also impacts subsequent surgical management. The identification and evaluation of intramammary lymph nodes can add value in the overall assessment of patients with breast cancer. The feasibility of noninvasive imaging modalities for SLN mapping in animal models has indicated a good potential for FNA biopsy in the subsequent investigation of SLNs identified noninvasively in humans. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

早期乳腺癌前哨淋巴结阳性患者腋窝管理方式的研究进展

乳腺癌的发病率居女性肿瘤之首,近年来随着诊断技术的发展及相关知识的普及,早期乳腺癌的检出率大大增加。淋巴结转移为乳腺癌最常见的转移方式,前哨淋巴结活检广泛用于术中评估肿瘤是否侵犯腋窝淋巴结。近年来有多项探讨关于前哨淋巴结局限阳性患者最佳腋窝管理方式的研究,引起较大争议,国内外临床处理的方式也不尽相同。本文将对前哨淋巴结阳性患者腋窝管理方式的最新研究进展作一综述。     

Evaluation of axillary lymph node status in breast cancer with MRI

Background  We performed a retrospective study to establish the optimal radiological criteria for axillary lymph node metastases from breast cancer by measuring all dissected nodes, and to determine whether magnetic resonance imaging (MRI) could reliably reveal axillary involvement. Methods  Pathological findings and MRI scans of 202 patients with invasive breast cancer were re-viewed. The long- and short-axis dimensions of all level I and II lymph nodes were measured micro-scopically, and then the long-to-short axis (L/S) ratio of each node was calculated. These parameters were compared with pathological nodal status to define radiological criteria for axillary involvement. MRI was carried out using T1-weighted spin-eho sequences in the coronal and sagittal planes. On MRI, every detected lymph node was measured and the shape of the nodal cortex was also examined. Then the diagnostic ability of MRI was assessed using these morphologic criteria. Results  On histopathological examinations of 4043 dissected lymph nodes, a long-axis dimension of 10 mm or larger combined with a long-to-short axis ratio of less than 1.6 was the most accurate criteria for predicting lymph node metastases. On MRI, eccentric cortical hypertrophy was seen in only metas-tatic axillae. When these morphologic features were used as criteria for malignancy, MRI had a sensi-tivity of 79%, a specificity of 93%, and an accuracy of 88%. In 16 of 17 false-negative axillae, MRI showed normally sized lymph nodes (<10 mm). Conclusion  Our study indicates that MRI is a useful diagnostic method for the evaluation of axillary nodal status, but is limited in the detection of small metastatic lymph nodes.     

Comparative efficacy of positron emission tomography and ultrasonography in preoperative evaluation of axillary lymph node metastases in breast cancer

PURPOSE: In primary breast cancer, axillary nodal status is the most powerful predictive factor of recurrence. However, axillary lymph node dissection may cause surgical complications. If preoperative evaluation of axillary lymph node metastases is possible, unnecessary axillary lymph node dissections can be avoided. The purpose of this study was to evaluate the efficacy of positron emission tomography (PET) on detection of axillary lymph node metastases in breast cancer. METHODS: PET scans of the axilla were obtained in 32 patients with primary breast cancer. All patients fasted for at least 4 hours before the examination. After transmission scans for attenuation correction were performed, emission scans after intravenous injection of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) were obtained. RESULTS: Overall accuracy of PET alone, ultrasonography alone, and in combination in the detection of axillary metastases were 82%, 79%, and 85% respectively. CONCLUSION: There were no significant differences between PET, ultrasonography, and PET in combination with ultrasonography regarding sensitivity, specificity and accuracy in the detection of axillary metastases.     

Role of FDG PET-CT in evaluation of locoregional nodal disease for initial staging of breast cancer

Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is not indicated or recommended in the initial staging of early breast cancer. Although it is valuable for detecting distant metastasis, providing prognostic information, identifying recurrence and evaluating response to chemotherapy, the role of FDG PET/CT in evaluating locoregional nodal status for initial staging of breast cancer has not yet been well-defined in clinical practice. FDG PET/CT has high specificity but compromised sensitivity for identifying axillary nodal disease in breast cancer. Positive axillary FDG PET/CT is a good predictor of axillary disease and correlates well with sentinel lymph node biopsy (SLNB). FDG PET/CT may help to identify patients with high axillary lymph node burden who could then move directly to axillary lymph node dissection (ALND) and would not require the additional step of SLNB. However, FDG PET/CT cannot replace SLNB or ALND due to unsatisfactory sensitivity. The spatial resolution of PET instruments precludes the detection of small nodal metastases. Although there is still disagreement regarding the management of internal mammary node (IMN) disease in breast cancer, it is known that IMN involvement is of prognostic significance, and IMN metastasis has been associated with higher rates of distant metastasis and lower overall survival rates. Limited clinical observations suggested that FDG PET/CT has advantages over conventional modalities in detecting and uncovering occult extra-axillary especially IMN lesions with upstaging the disease and an impact on the adjuvant management.