乳腺癌淋巴引流途径的临床研究

目的探讨乳腺癌时乳腺淋巴引流的特点。方法以2004年11月至2006年5月期间住院的206例乳腺癌患者为研究对象，其中191例术前行淋巴闪烁显像。用前哨淋巴结活检和腋窝溶脂后腔镜观察联合验证淋巴闪烁显像所见的乳腺淋巴引流途径和前哨淋巴结。结果肿瘤周围腺体实质和肿瘤被覆皮下联合注射示踪剂内乳前哨淋巴结显示率为46．8％。淋巴显像、前哨淋巴结活检和腋窝溶脂后腔镜3种方法联合观察发现乳腺淋巴经不同输入淋巴管直接引流到腋窝或内乳区；腋窝前哨淋巴结位于第2肋骨与胸大肌外缘交界处周围，少数患者有浅、深两组腋窝前哨淋巴结。内乳淋巴结转移率为26．2％，腋窝淋巴结转移≥4枚时内乳转移率为50．7％。第2肋间隙是内乳淋巴结最常见的转移部位。内乳淋巴结转移与肿瘤部位或大小无显著相关性。结论乳腺实质及皮肤的淋巴沿各自的集合淋巴管不经乳晕淋巴丛而直接汇人腋窝或内乳淋巴结；多数患者不同的淋巴管在腋窝汇人同一前哨淋巴结，少数汇人深浅不同组前哨淋巴结。有选择地行内乳淋巴结活检有助于乳腺癌的精确分期、治疗和预后判断。     

乳腺癌内乳前哨淋巴结活检术的研究进展

乳腺癌内乳淋巴结作为仅次于腋窝淋巴结的重要淋巴转移途径之一,其转移情况在乳腺癌的准确分期及个体化治疗中具有重要意义.内乳前哨淋巴结活检术可以通过微创的方式评估内乳淋巴结的转移情况,本文就乳腺癌内乳前哨淋巴结活检术的研究进展进行综述.     

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。     

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。     

临床腋窝淋巴结阳性乳腺癌患者内乳区前哨淋巴结活检术研究*

目的:评估临床腋窝淋巴结阳性乳腺癌患者行内乳区前哨淋巴结活检术（IM-SLNB）的临床意义。方法:2013年6 月至2014年10月对山东省肿瘤医院乳腺病中心就诊的64例临床腋窝淋巴结阳性的原发性乳腺癌患者行前瞻性单臂入组研究,采取腋窝淋巴结清扫术,同时均应用新的核素注射技术进行IM-SLNB。结果:64例患者中内乳区前哨淋巴结（IM-SLN）显像为38例,显像率为59.4%（38/ 64）。 38例IM-SLN 显像患者中IM-SLNB 成功率为100%（38/ 38）,并发症发生率为7.9%（3/ 38）,IM-SLN 转移率为21.1%（8/ 38）。 肿瘤位于内上象限和腋窝淋巴结转移数目较多的患者,其IM-SLN 转移率较高（P < 0.001 和P = 0.017）。 患者临床获益率为59.4%（38/ 64）,其中12.5%（8/ 64）另接受了内乳区放疗、46.9%（30/ 64）避免了不必要的内乳区放疗。结论:临床腋窝淋巴结阳性的乳腺癌应进行IM-SLNB,尤其对于肿瘤位于内上象限及怀疑存在较多腋窝淋巴结转移数目的患者,以获得内乳区淋巴结的转移状态,指导乳腺癌患者内乳区放疗。      

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。     

内乳淋巴结状态与乳腺癌转移复发相关性分析

0 引言腋窝淋巴结状况是乳腺癌分期和治疗方式选择的重要依据,而内乳淋巴结同样与预后密切相关.前者已常规进行淋巴清扫,后者因改良乳癌根治术的广泛开展而得到保留成为仅存的乳腺前哨淋巴结,目前是否作为常规检查,参与分期和指导治疗尚无肯定结论.本文收集经病理证实存在内乳淋巴结转移105例女性乳腺癌患者,观察治疗后内乳淋巴结存在状态与癌转移复发的相关性,为临床评估疗效与预后及合理的内乳淋巴结检查提供依据.     

乳腺癌内乳淋巴结精准分期与个体化治疗

内乳淋巴结（IMLN）和腋窝淋巴结（ALN）同是乳腺癌淋巴引流的“第1站”淋巴结,是淋巴分期、预后评估和治疗决策的重要依据。目前,ALN的处理已经接近个体化水平,但是,由于缺乏评估IMLN转移状况的微创技术,常导致分期不准确,治疗不足或过度。乳腺癌扩大根治术曾是获取IMLN转移数据的主要途径,但该术式在增加损伤的同时并未改善预后,导致外科医生对IMLN的关注度降低。近年来,多项研究显示出IMLN放疗的生存获益,但仅仅依靠转移风险（缺乏组织学诊断）来确定放疗指征很可能会导致治疗过度或不足。随着乳腺癌前哨淋巴结活检技术的发展,“新型示踪技术”引导内乳前哨淋巴结活检微创诊断技术可以准确、有效地评估IMLN转移状况,优化乳腺癌的区域淋巴分期,并指导精准的辅助治疗策略。     

早期乳腺癌前哨淋巴结活检的前沿进展

医学影像技术的飞速发展提高了早期乳腺癌腋窝淋巴结影像学诊断的能力,能够检测到腋窝淋巴结更早、更小的转移灶,通过影像学引导下穿刺活检明确淋巴结的转移状况,从而为患者提供更完善的术前腋窝分期。对于术前超声影像学检查为腋窝淋巴结阴性的患者是否可以避免术中腋窝前哨淋巴结活检,目前有两项大型临床试验正在进行中。山东大学附属山东省肿瘤医院乳腺病中心通过微泡超声造影显像技术引导腋窝前哨淋巴结术前穿刺活检,正在探索一种高效、准确和超微创的腋窝前哨淋巴结活检技术。术前影像学检查大大提高了临床腋窝淋巴结阳性患者的检出率,但也让一部分患者失去了通过腋窝前哨淋巴结活检替代腋窝淋巴结清扫的机会,对临床查体淋巴结阴性但超声发现可疑淋巴结并通过穿刺活检确诊转移的患者是否适合前哨淋巴结活检,本文也进行了相关的探讨和研究。另外,对内乳前哨淋巴结活检的相关研究结果进行了汇总。     

乳腺癌内乳区淋巴结诊疗的研究进展

内乳区淋巴结（internal mammary lymph node,IMLN）引流整个乳腺约25%的淋巴液,其转移状况为乳腺癌预后指标之一,也是确定分期和制定治疗方案的重要依据。内乳区前哨淋巴结活检术（internal mammary-sentinel lymph node biopsy,IM-SLNB）作为微创诊断技术实现对IMLN的评估,有助于为患者制定更为准确的个体化治疗方案。在乳晕周围腺体内增加注射部位和注射剂量的新型注射技术显著提高内乳区前哨淋巴结（internal mammary sentinel lymph node,IMSLN）检出率,使得常规开展IM-SLNB成为可能。随着内乳区淋巴引流规律的深入研究,新型注射技术引导下的IM-SLNB的准确性目前已得到初步验证。本文将对乳腺癌内乳区淋巴结诊疗的研究进展进行综述。      

Sentinel lymph node biopsy in breast cancer patients: the medical oncology perspective

Recent data indicates that the sentinel lymph node biopsy (SLNB) is a possible alternative to axillary lymph node dissection (ALND) in early breast cancer patients, with minimal risk of complications. From the medical oncologist's point of view, the impact of SLNB on the management of patients should consider if SLNB is useful to choose adjuvant treatment, if it is adequate to provide local control, and what is the significance of lymph node micrometastases on treatment and staging. Lymph node involvement has always been recognised as the most important prognostic factor in early-stage breast cancer, even if many other parameters have been evaluated in recent years. However, the lack of knowledge of nodal status in patients with false-negative SLNB seems to result in an undertreatment in a very low percentage of patients. Adjuvant chemotherapy and hormonal therapy with tamoxifen are associated with an absolute reduction of the risk of recurrence and death both in node-positive and in node-negative patients, then if patients are treated with modern adjuvant systemic therapy, any effect associated with false negative SLN should be minimised. The impact of axillary treatment on survival is still controversial, but in recent times axillary lymph node positivity is considered as an indicator for high risk of systemic diffusion of the disease rather than a possible origin of systemic metastases. The significance of occult sentinel lymph node metastases detected by immunohistochemistry (IHC) or molecular biology on prognosis is still uncertain. The new version of the staging system of breast cancer has recognised the need for a standard diagnostic approach and of a nomenclature system which also takes SLNB into account.     

精准治疗理念下乳腺癌患者腋窝淋巴结的评估与处理

腋窝淋巴结状态是乳腺癌分期、治疗决策以及预后判断的重要依据。精准医疗时代的到来更突显了腋窝淋巴结状态评估的重要性。除查体、超声等常规检查外,乳腺核磁、PET/CT以及近红外荧光、超顺磁性氧化铁、光声造影剂等新方法也可提供指导,其中前哨淋巴结活检是最重要的检查方法。新的临床证据表明前哨淋巴结阴性和前哨淋巴结1~2枚阳性的患者可以免除腋窝淋巴结清扫。炎性反应指标的比值可能是预测淋巴结转移的有用指标。部分高龄患者可以免除腋窝手术并获得良好预后。本文将围绕腋窝淋巴结的评估方法和处理争议进行梳理和总结,以期为精准治疗理念下乳腺癌患者腋窝淋巴结的处理提供新的指导。     

Risk of internal mammary lymph node metastases and its prognostic value in breast cancer patients

The risk of an internal mammary lymph node (IMN) metastasis and its prognostic value for patients with invasive breast cancer were assessed by evaluating 142 patients who had either a mastectomy with lymph node dissection or a biopsy of the IMN. By univariate analysis, overall survival significantly correlated with the patient's age, clinical axillary node status, tumor size, and DNA ploidy, as well as histologically confirmed axillary and IMN metastases. By multivariate analysis, however, only the presence of axillary and IMN metastases appeared to be an important independent factor affecting survival. However, the incidence of IMN metastases was associated significantly with age, clinical tumor and axillary node status, tumor size, axillary lymph node metastases, and DNA ploidy. Accordingly, the patient's age, tumor size, DNA ploidy, and axillary lymph node metastases proved to be effective variable for discrimination. Consequently, in predicting the presence of IMN metastases, a diagnostic accuracy of 82%, a sensitivity of 84%, and a specificity of 82% can be achieved by a discriminant function. We conclude that the discriminant function with these four variables is effective in assessing the risk of IMN metastases. © 1993 Wiley-Liss, Inc.     

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.     

Prognosis of breast cancer patients treated with sentinel node biopsy in Japan

BACKGROUND: Sentinel node biopsy predicts accurate pathological nodal staging. The survival of node-negative breast cancer patients should be evaluated between the patients treated with sentinel node biopsy alone and those treated with axillary lymph node dissection. METHODS: Ninety-seven patients with negative axillary nodes underwent sentinel node biopsy immediately followed by axillary lymph node dissection between January 1998 and June 1999 (the ALND group). Since then, if sentinel lymph nodes were negative on the frozen-section diagnosis, 112 patients underwent sentinel node biopsy alone without axillary lymph node dissection between July 1999 and December 2000 (the SNB group). We retrospectively observed the outcome of the two study groups. RESULTS: Median follow-up was 52 months in all patients. Relapse-free survival rates at 3 years in the ALND and SNB groups were 94% and 93%, respectively. Five of the 112 patients in the SNB group had overt axillary metastases. Three of them with axillary metastases alone were treated with delayed axillary lymph node dissection. These three patients have been free of other events for 3 years after local salvage treatment. CONCLUSIONS: Sentinel node biopsy will emerge as a standard method to diagnose axillary nodal staging for clinically node-negative breast cancer patients.     

T1 breast cancer: identification of patients at low risk of axillary lymph node metastases

Objective. The status of the axillary lymph nodes is one of the most important prognostic factors in patients with breast cancer. A panel of molecular markers of tumor aggressiveness in addition to conventional clinical and histopathologic features were analyzed in an attempt to identify a subgroup of patients with a low risk of axillary lymph node metastases. Material and methods. Data from 358 patients with T1 breast cancer who underwent level I/II axillary lymph node dissection (ALND) were investigated. Hormone receptor status, Ki-67, S-phase fraction, DNA ploidy, HER-2/neu, p53, epidermal growth factor receptor, urokinase type plasminogen activator, plasminogen activator inhibitor-1, bone marrow micrometastases as well as patient age, menopausal status, tumor site, tumor size, histologic type, tumor grade, carcinoma in situ, multifocality, and lymph vascular invasion (LVI) were studied to predict axillary lymph node status. Results. In a multivariate logistic regression analysis LVI (present v.s. not present), Ki-67 (18% v.s. <18%), tumor size (1.1–2 cm v.s. 1 cm), and histologic grade (G3 v.s. G1/2) were identified as independent predictive factors of axillary lymph node metastases. Approximately 13% of patients (n = 47) with well or moderately differentiated tumors less than or equal to 1 cm, no lymph vascular invasion, and a low Ki-67 staining were identified as having a low risk of axillary lymph node metastases of 4.3%. However, 20 patients with all four unfavorable predictive factors had a 75% incidence of axillary lymph node involvement. Conclusion. Primary tumor characteristics can be used to identify a subgroup of patients with a low risk of axillary lymph node metastases in T1 breast cancer. Preoperative risk assessment might be used to omit routine ALND in those patients at low risk of axillary lymph node metastases.     

Added value of ultrasound in screening the clinically negative axilla in breast cancer

BACKGROUND: For staging purposes in breast cancer it is current practice to perform a sentinel node biopsy in a clinically negative axilla, followed by an axillary lymph node dissection if metastases are found in the sentinel node. To limit the number of surgical procedures it is therefore of importance to try and identify as much patients as possible who have axillary metastases. Clinical staging of the axillary nodes in breast cancer is mainly based on palpation, but ultrasound has been shown to be of additional value in detecting pathological nodes. METHODS: In this paper, we report our results of screening 131 breast cancer patients without palpable axillary nodes through ultrasound. RESULTS: Out of the 53 patients with axillary node involvement, 18 were identified as such by our radiologist, resulting in a detection score of 34%. DISCUSSION: This high rate is probably reached because of the limited number of radiologists performing this procedure, thereby rapidly increasing their experience.