Detection and Significance of Occult Axillary Metastatic Disease in Breast Cancer Patients

▪ Abstract: After clinical staging, the single most important prognostic factor for patients with newly diagnosed primary breast cancer is the presence or absence of detectable metastases to axillary lymph nodes when examined by conventional light microscopy. More sensitive methods of determination of lymph node status, such as evaluation of serial sections, immunohistochemical staining, and use of molecular biological assays increase the rate of detection of micrometastases. Although the feasibility of enhanced detection of occult axillary metastatic disease is well established, the prognostic significance of such detection is only recently starting to emerge. Furthermore, the enormous recent interest in the application of sentinel lymph node biopsy as an alternative to the evaluation of the entire axilla in patients with breast cancer makes the first-time detailed evaluation for micrometastases practically feasible. In this review the different methods of detecting micrometastatic disease in the axilla and the significance of such findings are discussed. ▪     

Axillary Node Sample to Evaluate the Axilla

Lymphatic drainage from the breast is principally to the ipsilateral axilla. In patients with breast cancer the status of the lymph nodes in the axilla is an important prognostic factor and can be used to determine local and systemic therapies. Clinical assessment of the axillary lymph nodes is unreliable, and imaging techniques, although they show some promise, are at present not practical. Standard policy for management of the axilla is clearance of the axillary lymph nodes (either level II or level III), which is justified on the grounds that it both stages and treats the axilla. In those who are axillary node-negative, however, it is an unnecessary operation and is associated with some morbidity. Various methods to obtain lymph nodes for histologic assessment in an attempt to stage the axilla have been tried. The pectoral node biopsy, where a single node is removed from the axillary tail, has been shown to be unreliable. A triple-node biopsy (pectoral node, apical node, internal mammary node) provides excellent prognostic data but is difficult to perform in patients who have been treated by breast conservation. The four-node sampling technique has been evaluated in Edinburgh in two randomized trials comparing node sampling to level III axillary clearance. It was shown to be reliable for staging the axilla; and in those who are node-negative no further treatment is required. Detailed morbidity has been assessed in patients who underwent axillary clearance; and node sampling plus radiotherapy and node sampling without radiotherapy showed that those with node sampling had the least morbidity. Those who had node sampling plus radiotherapy have reduced movement around the shoulder joint, and the axillary clearance group have increased swelling of the upper limb and slightly reduced abduction. The sentinel node biopsy is presently being assessed in several centers by randomized studies. Several large series have shown the technique to be accurate (98%) when the sentinel node is identified (around 90% of cases).     

Management of the Axilla in Women With Breast Cancer: Current Clinical Practice and a New Selective Targeted Approach

Background Axillary nodal status is the most important prognostic factor for patients with breast cancer. Clinical assessment and imaging modalities are not always reliable. Surgical removal and histopathological examination of axillary lymph nodes remain essential methods of staging the axilla. However, the optimal management of the axilla remains uncertain. Methods We performed Medline searches to identify relevant systematic reviews, meta-analysis, and nonrandomized and randomized controlled trials for the past 5 years (up to December 2007), as well as important historical articles and clinical guidelines relating to management of the axilla in women with breast cancer. Results Axillary lymph node dissection (ALND) has been the standard surgical approach for many years. It is, however, associated with marked morbidity; survival benefit remains uncertain. Axillary node sampling, widely practiced in the United Kingdom, is a reliable alternative procedure in staging the axilla, with less morbidity. Sentinel lymph node biopsy (SLNB) has become an accurate method for staging the axilla in women with operable, clinically node-negative breast cancer. SLNB alone appears to be a safe and acceptable procedure for patients with uninvolved SLNs. Completion ALND or axillary radiotherapy remains the standard treatment for patients with tumor-involved SLNs. SLNB is associated with less morbidity than ALND. However, long-term follow-up and therapeutic outcomes are being awaited from randomized controlled trials. Conclusions Several procedures are available for staging and treating the axilla. A tailored surgical approach, with careful assessment of risk-benefit and patient preference, is guiding the evolving modern management of the axilla for women with breast cancer.     

Sentinel lymph node biopsy or detection of micrometastasis in bone marrow: which might be an alternative to axillary lymph node dissection in breast cancer patients?

Axillary lymph node status has limited prognostic significance in breast cancer patients and much improvement can be made. Sentinel lymph node biopsy is emerging as an alternative to axillary lymph node dissection for staging, but its prognostic relevance is still uncertain. Detection of micrometastases in sentinel nodes and bone marrow may provide more information, but the clinical significance still needs to be confirmed by ongoing large trials. In this review, we focus on the possibility of sentinel lymph node biopsy or detection of bone marrow micrometastasis replacing traditional axillary lymph node dissection.     

Surgical axilla dissection. Technical standard or obsolete method?

Axillary lymph node status remains the single most important prognostic parameter and has crucial therapeutic implications in patients with breast carcinoma. Surgical dissection of the axilla is commonly regarded as the standard procedure of axillary staging, its sensitivity and specificity being 99% and 100%, respectively. Apart from giving reliable information on the individual prognosis axillary dissection also contributes to efficient local tumor control in the axilla, as it reduces the risk of local recurrence to less than 1.4% if more than 10 lymph nodes are removed. Alternative, less or non-invasive axillary staging methods have either not yet been sufficiently standardized (immunoscintigraphy, PET-scan, prediction of axillary lymph node status by means of individual risk factors) or are associated with a considerable risk of false-negative staging (up to 50% of patients with positive axillary lymph nodes are not detected by palpation alone, ultrasonography or CT-scan). The basic principles of axillary sampling and axilloscopic dissection are questionable because the number of lymph nodes removed during these procedures is commonly less than 10. With its sensitivity/specificity being comparable to that of standard axillary dissection sentinel lymph node biopsy represents a highly promising approach which will in the future potentially lead to significant optimization of the clinical management of patients with breast cancer, especially those diagnosed in early stages (T1 a, T1 b and T1 c).     

��״�ٰ��淶������������¼�������

??Standard, controversy and consensus of axillary lymph nodes dissection in breast cancer MA Rong, ZHANG Kai. Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan 250012, China
Corresponding author: MA Rong, E-mail: marongw2000@163.com
Abstract There are many effective methods for breast cancer treatment, surgery is the basis of management of breast cancer. Local control is the symbol of a successful operation. Lymph node status is not only the most important factor in predicting survival in breast cancer, but also the guider of further treatment. Axillary lymph node dissection and pathological examination remains standard management of the axilla and assessment of breast cancer patients. For clinical axillary lymph node metastasis patients, axillary lymph node dissection is critical. Sentinel lymph node biopsy has become standard care for management of the axilla in clinical axillary node-negative early breast cancer patients. It is clear that axillary lymph node dissection should be strongly considered in the management of the sentinel lymph node positive axilla. Omission of axillary lymph node dissection for breast cancer patients with 1-2 positive sentinel lymph nodes is still controversial .     

Sentinel lymph node drainage in multicentric breast cancers

Axillary lymph node status is the most important prognostic marker in patients with breast cancer; the presence of axillary metastases impacts prognosis as well as subsequent systemic therapy. Axillary lymph node dissection (ALND) is associated with significant morbidity and psychological distress; the introduction of sentinel lymph node (SLN) biopsy with lymphatic mapping affords the ability to identify those patients most likely to benefit from ALND, sparing node-negative patients. The lymphatic drainage of the breast is poorly understood, and the situation is further complicated by the lack of standardization of the SLN biopsy technique among institutions. Multicentricity has generally been considered to be a contraindication to SLN biopsy due to concerns about potential inaccuracies. Here we report five cases of patients with multicentric breast cancers (two tumors in two distinct quadrants). In each case, injection of one site with technetium-labeled sulfur colloid and the second site with isosulfan blue dye resulted in successful identification of at least one node that was both hot and blue within the axilla. These observations suggest that the lymphatic drainage of the entire breast coincides with drainage of the tumor bed, regardless of the quadrant. However, further studies are needed to validate the accuracy of SLN biopsy in multicentric breast cancers.     

Case report: complete lymphatic staging in breast cancer by lymphoscintigraphy and sentinel node biopsy

The status of the lymph nodes in the axilla and in the internal mammary chain are the most significant prognostic factors for survival in breast cancer. Lymphoscintigraphy shows lymphatic drainage outside the axilla, most often to the internal mammary nodes, usually in 20% to 30% of breast cancer patients, when intraparenchymal techniques of the radioactive tracer injection are used. Lymphoscintigraphy and sentinel node biopsy are potential tools for more accurate staging in breast cancer, because they provide additional information compared to axillary staging alone. We report a breast cancer case with 10 hot spots in five different lymphatic basins (axilla, internal mammary chain, intramammary, infraclavicular, and high interpectoral) in the lymphoscintigraphy.     

乳腺癌行腋窝淋巴结清扫规范、争议与共识

乳腺癌的有效治疗方法很多,但外科手术是公认的乳腺癌治疗的基础。手术成功与否的最根本标志是肿瘤手术区域的局部控制。腋窝淋巴结受累的程度是预测乳腺癌术后复发和生存,指导进一步个体化治疗的最为重要指标。规范的腋窝淋巴结清扫和病理检查对乳腺癌的治疗至关重要。术前判断存在腋窝淋巴结转移的乳腺癌病人,腋窝淋巴结清扫是乳腺癌手术的规范和要求。术前临床诊断无腋窝淋巴结转移（cN0）的早期乳腺癌病人,如果前哨淋巴结活检阴性可不做进一步的腋窝淋巴结清扫也已成为共识。对于前哨淋巴结1或2枚阳性的乳腺癌病人可以不行腋窝淋巴结的清扫的观点仍然存在争论。     

Axillary Dissection over the Years: Where To from Here?

Management of the axilla in breast cancer patients has been a subject of intense debate and controversy. Axillary lymph node status is still considered to be the single most important prognostic indicator in breast cancer patients. Despite a tendency toward a conservative approach for the surgery of primary breast carcinoma, axillary lymph node dissection (ALND) has remained an integral part of breast cancer management for more than a century. Among patients with T1/T2 tumors, up to 70% have a negative axillary dissection, and more than 50% of these node-negative patients develop morbidity related to ALND. It is ironic that the extent, morbidity, and cost of a staging procedure (ALND) is more than that of the surgical treatment of the primary tumor. We must readdress the question of axillary management in breast carcinoma in the light of information gained from the sentinel node biopsy trials around the world. We review the historical milestones and various modalities used for axillary management, discuss the concept of sentinel node biopsy for breast carcinoma, and propose a management plan.     

Axillary Irradiation as an Imperative Alternative to Axillary Dissection in Clinically Lymph Node-Negative but Sentinel Node-Positive Breast Cancer Patients?

At the moment, positive sentinel lymph node dissection (SLND) of the axilla is followed by axillary lymph node dissection (ALND) as standard of care. Recent data proves that omitting ALND after positive SLND in clinically lymph node-negative early stage breast cancer patients is feasible with low recurrence rates. The well known effect of radiotherapy to destroy occult tumor cells highly contributes to these results as a large extent of level I and II lymph nodes are unavoidably included in standard tangential radiation treatment fields. Reviewing the up to date published data on axillary lymph node treatment with radiotherapy, we hypothesize that full dosage coverage of level I and II of the axilla in early stage breast cancer will improve outcome and should be further evaluated.     

Prediction of non-SN involvement in patients with SN isolated tumor cells or micrometastases

Sentinel lymph node biopsy has allowed improved staging of the axilla with reduced morbidity in breast cancer patients. However, as with any new technology there are questions as to how to best implement the technique into clinical practice. Changes in the staging system for breast cancer have incorporated sentinel lymph node biopsy findings, resulting in questions as to how to manage the remainder of the axilla when there is low volume disease in the sentinel lymph nodes. The use of the sentinel lymph node to predict additional positive nodes and to direct surgical management of the axilla and adjuvant systemic and radiation therapy is reviewed.     

Clinical relevance of sentinel lymph nodes outside the axilla in patients with breast cancer

BACKGROUND: Lymphatic mapping in patients with breast cancer can reveal sentinel lymph nodes that are not located at level I-II of the axilla. Little is known about the clinical relevance of these nodes. METHODS: Some 113 consecutive patients with clinical stage T1-3 N0 M0 breast cancer were studied. Based on preoperative lymphoscintigraphy, sentinel node biopsy was performed guided by a gamma probe and patent blue dye. All sentinel nodes that were visible on lymphoscintigraphy were sought. Pathological examination of the sentinel nodes included step-sections and staining with CAM 5. 2. Axillary node dissection was performed regardless of sentinel lymph node status. RESULTS: Twenty-one (19 per cent) of 113 patients had sentinel lymph nodes outside level I-II of the axilla, mostly in the internal mammary chain. Twenty-two of the 30 sentinel nodes at these sites were harvested. Three patients had sentinel nodes only outside the axilla. Four other patients had metastases outside the axilla. This changed postoperative treatment in three patients. No postoperative complication occurred. CONCLUSION: Sentinel lymph nodes outside level I-II of the axilla were present in 19 per cent of patients with breast cancer in this series. Biopsy of these nodes was technically demanding but was performed without additional morbidity. The clinical impact was limited; treatment changed in only 3 per cent. Presented to the 52nd annual meeting of the Society of Surgical Oncology in Orlando, Florida, USA, March 1999 and the First International Congress on the Sentinel Node in Diagnosis and Treatment of Cancer in Amsterdam, The Netherlands, April 1999, and published in abstract form as Eur J Nucl Med 1999; 26(Suppl): S71     

Reoperative sentinel lymph node biopsy in ipsilateral breast cancer relapse

Sentinel lymph node biopsy (SLNB) is controversial following ipsilateral breast tumour relapse (IBTR) and previous axillary surgery. We retrospectively assessed the feasibility, outcomes and utility of this procedure. Eighteen patients with IBTR who underwent reoperative SLNB were identified. Fifteen women had previously undergone axillary lymph node dissection and three SLNB for breast cancer. Twelve of 16 patients underwent successful lymphoscintigraphy (LSG). Lymphatic drainage patterns varied widely - ipsilateral axilla (5), contralateral axilla (5), and ipsilateral internal mammary (5). Two patients had drainage to more than one nodal basin. Nine of 12 patients demonstrated drainage outside of the ipsilateral axilla. Reoperative SLNB was successful in 12/18 of patients - 4 ipsilateral axilla, 1 ipsilateral internal mammary, 1 ipsilateral intramammary, 4 contralateral axilla. Two patients had sentinel nodes in multiple nodal basins. Positive sentinel node was found in one successful case (contralateral axilla) and isolated tumour cells in two (1 contralateral axilla, 1 ipsilateral internal mammary). In conclusion, reoperative SLNB is feasible. Lymphatic drainage patterns vary widely and preoperative LSG is vital to facilitate identification of sentinel nodes in unusual sites. Its prognostic and therapeutic significance warrants further study.     

Radical mastectomy with parasternal node dissection or radiation to the parasternal region for breast cancer of medial or central location

In order to establish a therapeutic approach for primary breast cancer of medial and central origin, we reviewed 183 patients who had been treated by one of the following three modalities at the Second Department of Surgery, Osaka University Medical School between January, 1965 and December, 1980. Group A (n=70): standard radical mastectomy alone; Group B (n=34): standard radical mastectomy followed by postoperative irradiation to the parasternal and supraclavicular regions, and; Group C (n=62): extended radical mastectomy that included removal of the parasternal lymph nodes. The background factors of the three groups were not significantly different. The overall survival five and ten years following surgery in the three groups were 91 per cent and 79 per cent in group A, 82 per cent and 67 per cent in group B, and 82 per cent and 70 per cent in group C, respectively, showing no significant difference in overall survival among the three groups. When the patients were classified according to the extent of axillary lymph node involvement, there was no difference in survival among the three treatments in patients who had less than three lymph node metastases in the axilla. However, treatment of the parasternal lymph nodes improved survival in the patients who had more than four lymph node metastases in the axilla. Parasternal lymph node involvement definitely worsened the prognosis, showing it to be a good prognostic factor. Thus, extended radical mastectomy should be considered for patients with breast cancer of medial or central location, when extended axillary lymph node involvement is found.     

Enhanced postoperative lymphatic staging of malignant melanoma by endoscopically assisted iliacoinguinal dissection

Radical lymphadenectomy for malignant melanoma continues to be controversial. In order to reduce morbidity but preserve prognostic informations, a minimally invasive technique for the iliac part of dissection was developed. We evaluated the practicability of this intervention under routine conditions as well as its prognostic impact. A total of 106 patients with tumor cell involvement of at least one inguinal lymph node underwent open inguinal dissection combined with a minimally invasive iliac dissection. Perioperative and postoperative data on morbidity, survival, and histopathological features of the primary and the dissected specimens were collected. Histopathological data were evaluated statistically for their prognostic relevance. Of the 106 patients, 38 showed evidence of additional metastases in the resected specimen, of which 11 cases were related to the iliac portion. Detection of lymph node metastases in the specimen was significantly correlated with a poorer prognosis, while out of all factors implicated, a new prognostic factor comprising iliac tumor involvement and primary tumor ulceration showed the strongest statistical correlation with prognosis. The median dissection time was 137 min, 58 min devoted to the iliac part. Complications necessitating reoperation (n = 7) related only to the inguinal wound area. Minimally invasive iliac lymph node dissection is ready for clinical routine. The additional information obtained by the iliac dissection—in particular, in combination with primary tumor ulceration—is of important prognostic relevance. Further development of this technique performing a completely minimally invasive ilioinguinal dissection may confer additional advantages.     

肝内胆管癌淋巴结清扫的热点与争议

肝内胆管癌是一种高度侵袭性的恶性肿瘤,近年来发病率逐年升高,根治性手术切除被认为是可能治愈的唯一方法.淋巴结转移是手术预后的高危因素,在肝内胆管癌根治性切除术中,淋巴结清扫问题仍存在很多争议,其中淋巴结清扫与否,淋巴结清扫的方式和范围,以及清扫的意义和价值更是当下研究的热点.本文就肝内胆管癌淋巴结清扫的热点与争议进行了...     

Non-sentinel lymph node metastases in breast cancer patients with metastatic sentinel nodes

BACKGROUND: Sentinel lymph node biopsy (SLNB) has been shown to be relatively accurate in axillary nodal staging in breast cancer. In more than half of the patients with metastatic sentinel lymph node (SLN), the SLN was the only lymph node involved in the axilla. Methods: A retrospective analysis was performed for those female Chinese breast cancer patients who underwent SLNB. All patients had axillary dissection after SLNB. Those patients with metastatic SLN were selected for analysis. Various tumour factors and SLN factors were analysed to study the association with residual lymph node metastasis. Results: A total of 139 SLNB was performed. The success rate of SLN localization, false negative rate and accuracy were 92%, 9% and 95%, respectively. Fifty-five patients had metastases in the SLN. In 38 patients (69%), SLN was the only lymph node involved in the axilla. Tumours <3 cm, a single metastatic SLN, presence of micro metastases and the absence of extracapsular spread in the SLN were associated with the absence of metastasis in the non-sentinel lymph nodes. Conclusion: Sentinel lymph node biopsy is accurate in the nodal staging of Chinese breast cancer patients. Several factors such as tumour <3 cm, a single metastatic SLN, micro metastases and the absence of extracapsular spread in the sentinel node(s) are useful predictors for the absence of residual disease in the axilla. With further studies and verification, these factors may prove to be important in determining which patients with metastatic SLN will require further axillary treatment. Until such information is available, axillary dissection should be performed when positive sentinel nodes are found.     

Sentinel Node Biopsy in Breast Cancer: An Overview

The most powerful predictor of survival in breast cancer is the presence or absence of lymph node metastases. Lymphatic mapping and sentinel node biopsy is a new technique that provides more accurate nodal staging compared to routine histology for women with breast cancer without the morbidity of a complete lymph node dissection. Sentinel lymph node biopsy is a more conservative approach to the axilla that requires close collaboration between the surgical team, nuclear medicine, and pathology. National trials are investigating the clinical relevance of the upstaging that occurs with a more intense examination of the sentinel node. Since complaints due to the axillary node dissection are a common occurrence after definitive breast cancer surgery, if the side effects of the level I and II node dissection can be avoided, particularly in the node-negative population, a major advance in treating this disease will be made.     

The role of lymph node sampling and radiotherapy in the management of the axilla in early breast cancer

Management of the axilla in early breast cancer is an issue of ongoing debate. We reviewed our experience in 312 patients who underwent axillary lymph node sampling between 1994 and 1998, of whom 81 patients (24%) had axillary lymph node metastasis. There have been two axillary recurrences, one associated with local recurrence to the breast and one presenting with distant metastasis. There were no patients with isolated axillary disease as their only site of recurrence and no axillary failures in the node-positive group treated with axillary sampling and radiotherapy. Axillary lymph node sampling effectively stages the axilla. This can safely be followed by radiotherapy to the axilla in case of lymph node metastasis. Axillary lymph node sampling forms a sound basis to develop new techniques, such as sentinel lymph node biopsy currently investigated by ongoing trials.