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。     

Preoperative lymphoscintigraphy and dynamic sentinel node biopsy for staging penile cancer: results with pathological correlation

PURPOSE: We assessed the sensitivity of preoperative lymphoscintigraphy and dynamic sentinel node biopsy for staging the inguinal region of patients with penile cancer and no palpable inguinal adenopathy. MATERIALS AND METHODS: The records of 31 patients with invasive penile cancer and nonpalpable (29) or nonsuspicious (2) inguinal lymph nodes were reviewed. Preoperatively lymphoscintigraphy plus dynamic sentinel node biopsy with (99m)technetium labeled sulfur colloid and isosulfan blue dye was performed in 21 patients and dynamic sentinel node biopsy alone with blue dye only was done in 10. All patients underwent superficial lymph node dissection regardless of preoperative lymphoscintigraphy or dynamic sentinel node biopsy findings to establish pathological nodal status. RESULTS: Six of 32 groins that showed drainage on preoperative lymphoscintigraphy had inguinal node metastasis, as did 1 of 10 that was drainage negative. The sensitivity of preoperative lymphoscintigraphy drainage for cancer detection was 86%. Using dynamic sentinel node biopsy with blue dye plus radiotracer 5 sentinel lymph nodes were positive for cancer, although 2 false-negative results were obtained. Thus, the sensitivity of dynamic sentinel node biopsy per groin for cancer detection was 71%. CONCLUSIONS: In our experience preoperative lymphoscintigraphy and dynamic sentinel node biopsy as currently performed remain insufficient for detecting occult inguinal disease. Superficial lymph node dissection remains the gold standard for detecting inguinal microscopic metastasis in select patients.     

Management of the axilla in early breast cancer: is it time to change tack?

The standard surgical treatment of the axilla in patients with early breast cancer is about to undergo a radical change. Although axillary dissection is an excellent procedure for both staging and local control, particularly in the clinically positive axilla, it has considerable morbidity and may understage a significant proportion of patients, because it will usually miss micrometastases that can occur in approximately 10% of ‘node negative’ patients. An increasing number of patients whose tumours are either non‐invasive (ductal carcinoma in situ; DCIS), micro‐invasive, tubular cancers or low‐grade T_1a tumours without lymphovascular invasion may be spared axillary surgery because the risk of axillary disease is 0–3%. Many studies, both prospective trials and large retrospective series, show that axillary radiotherapy alone provides similar local control rates to axillary dissection in patients with clinically negative axillas. Primary treatment of the axilla with radiotherapy alone, however, does not allow appropriate staging. Sentinel lymph node biopsy is being increasingly used in patients with breast cancer to provide this information. When a sentinel node is identified it is equal to or better than axillary dissection for staging the axilla and, if the node is positive, it will help select patients who should then proceed to further axillary surgery or axillary radiotherapy. Although sentinel lymph node biopsy is being rapidly adopted in many centres worldwide, the results of randomized controlled trials are needed before it can be recommended as the standard of care.     

Surgical management of the axilla: do intramammary nodes matter?

Background

The therapeutic significance of intramammary lymph nodes is uncertain. The purpose of this study was to identify the appropriate surgical management of the axilla in intramammary node-positive patients undergoing sentinel lymph node (SLN) biopsy.

Methods

A retrospective review of consecutive patients staged between September 1996 and December 2004 was performed. Intramammary node identification and pathologic findings were compared with the status of axilla.

Results

Among 7,140 patients, intramammary nodes were identified in 151 (2%). Positive intramammary nodes were identified in 36 patients (24%). Axillary disease was identified in 61% of intramammary node-positive patients. No additional axillary disease was identified when axillary lymph node dissection was performed in intramammary node-positive patients with negative axillary SLN biopsy results.

Conclusions

The results suggest that completion axillary lymph node dissection may be based on the status of axillary SLN biopsies in clinically node negative patients when intramammary lymph node metastases are identified in the breast specimens.     

An axillary recurrence of breast cancer following a negative sentinel lymph node biopsy

Abstract: In many parts of the United States, lymphatic mapping and sentinel lymph node biopsy has almost replaced axillary lymph node dissection (ALND) as the axillary staging procedure of choice for small, clinically node-negative breast cancers. However, the long-term outcome of patients undergoing a sentinel lymph node biopsy as the only axillary procedure in patients with tumor-free sentinel nodes remains to be determined. We present the first reported case of axillary recurrence in a patient with breast cancer following a tumor-negative sentinel lymph node biopsy. Whether sentinel lymph node biopsy can replace ALND in the management of patients with early breast cancer remains to be answered.     

Twenty‐five years of change in the management of the axilla in breast cancer

Sentinel lymph node (SLN) biopsy is now used worldwide. It has led to many changes in how we manage the axilla in patients with breast cancer. This review covers four areas of management of the axilla in breast cancer: assessing the clinically node‐negative axilla, managing the clinically negative axilla found to be involved at SLN biopsy, management of the clinically positive axilla in the context of neo‐adjuvant chemotherapy, and treatment of the diseased axilla when radical therapy is required. We suggest that the evidence supports an optimum number of 3 nodes to be removed for accurate SLN biopsy. Breast cancer departments that have not adopted Z0011 patient management cannot continue to avoid change. The evidence is clear: Not all patients with limited axillary nodal disease on sentinel node biopsy need axillary lymph node dissection. For patients who do need axillary treatment, axillary radiotherapy continues to be under‐used. Patients undergoing neo‐adjuvant chemotherapy can be safely assessed by post‐therapy SLN biopsy, with retrieval of any previously biopsied involved nodes by targeted axillary dissection. There is much to support the trend to doing less in the axilla. We are obliged to act based on the available robust clinical trial data in a way that limits morbidity while at the same time does not increase the risk of disease recurrence.     

The Role of Sentinel Lymph Node Biopsy with Blue Dye Alone in Breast Cancer Patients with Excisional Biopsy

Purpose : Sentinel lymph node biopsy (SLNB) appears to offer an excellent alternative method to routine axillary lymph node dissection for staging patients with breast cancer. The aim of this study is to evaluate the effect of excisional biopsy on identification and false negative rate of sentinel lymph node biopsy with blue dye alone in breast cancer patients with clinically negative axilla.

Material and Methods : From March 1998 to March 2003, 266 consecutive sentinel lymph node biopsies (SLNB) were performed using isosulfan blue dye alone. Patients were divided into two groups. One hundred and four patients (39.1%) had previously undergone an excisional biopsy (Group I); in 162 patients (60.9%), pre-operative diagnosis was obtained by either fine-needle aspiration biopsy (FNAB) or core biopsy (Group II). Following sentinel lymph node biopsy, all patients had axillary lymph node dissection (ALND). Data concerning patients, sentinel lymph nodes and the status of the axilla were collected and compared using Fisher’s exact test. A p value of less than 0.05 was considered statistically significant.

Results : The sentinel lymph node was successfully identified by blue dye in 94.3% (251/266) of patients. Mean lymph nodes removed from the axilla was 19 (range 11–36) and the mean number of sentinel nodes was 2 (range 1–5). The identification and false negative rate were unrelated to size, type or location of the tumour, or a previous surgical biopsy. Conclusions : SLNB with blue dye for evaluation of the axilla is a rapid and accurate technique that provides increased efficacy in the detection of lymphatic metastasis when careful pathologic evaluation with serial sections is performed. The risk-benefit analysis of lymphatic mapping with blue dye provides improvement in staging, with reduced morbidity and hospital stay, and the elimination of general anaesthesia. The technique may also be used safely and accurately in breast cancer patients with excisional biopsy.     

Axillary staging using positron emission tomography in breast cancer patients qualifying for sentinel lymph node biopsy

Axillary lymph node dissection (ALND) is the standard of care for nodal staging of patients with invasive breast cancer. Due to significant somatic and psychological side effects, replacement of ALND with less invasive techniques is desirable. The goal of this study was to evaluate the clinical usefulness of axillary lymph node (ALN) staging by means of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in breast cancer patients qualifying for sentinel lymph node biopsy (SLNB). FDG-PET was performed within 1 week before surgery in 24 clinically node-negative breast cancer patients with tumors smaller than 3 cm. Sentinel lymph nodes (SLNs) were identified by preoperative lymphoscintigraphy following peritumoral technetium 99m-labeled colloid albumin injection, and by intraoperative gamma detector and blue dye localization. Following SLNB, a standard ALND was performed. Serial sectioning and immunohistochemistry of the SLN as well as standard histologic examination of the non-SLN was performed. FDG-PET detected all primary breast cancers. Staging of ALNs by PET was accurate in 15 of 24 patients (62.5%), whereas PET staging was false negative in 8 of 10 node-positive patients and false-positive in 1 patient. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for nodal status was 20%, 93%, 67%, and 62%, respectively. The mean diameter of false-negative ALN metastases was 7.5 mm (range 1-15 mm). Lymph node staging using FDG-PET is not accurate enough in clinically node-negative patients with breast cancer qualifying for SLNB and should not be used for this purpose.     

乳腺癌新辅助治疗前哨淋巴结处理原则

前哨淋巴结活检及新辅助治疗已成为乳腺癌综合治疗的重要措施，也是个体化治疗的重要体现。乳腺癌新辅助治疗具有较高的腋窝淋巴结控制率，如何在乳腺癌新辅助治疗病人中精准、高效实施前哨淋巴结活检引起越来越多的关注。新辅助治疗前后腋窝淋巴结状态的精准评估是实施前哨淋巴结活检的基础。对于新辅助治疗前腋窝淋巴结阴性的病人，推荐新辅助治疗后行前哨淋巴结活检。对于新辅助治疗前腋窝淋巴结阳性，新辅助治疗后淋巴结转阴的病人，需在双示踪、前哨淋巴结检出数≥3枚及阳性淋巴结靶向切除的前提下，进行前哨淋巴结活检，在我国医疗资源现状下，需结合示踪药物的可及性及技术条件，谨慎选择适宜病人。     

Failure of sentinel lymph node mapping in breast cancer patients qualified for treatment sparing axillary lymph nodes—Clinical importance and management strategy—One‐center analysis

Sentinel lymph node biopsy (SLNB) is a standard in diagnostic and therapeutic management of patients with nonadvanced invasive breast cancer. The aim of this paper was to evaluate the clinical importance of the failure of sentinel lymph node (SLN) identification during SLNB performed to spare axillary lymph nodes. A total of 5396 patients with invasive breast cancer qualified for SLNB, treated in a period from Jan 2004 to June 2018. All cases of the failure of SLN identification and reasons underlying this situation were analyzed retrospectively. In 196 (3.6%) patients, SLN was not identified (group I), and this resulted in a simultaneous axillary lymph node dissection. 48.5% patients from this group were diagnosed with cancer metastases to lymph nodes (vs 23.6% patients with SLN removed—group II, P < .00001)—stage pN1 in 44.2% of the cases, stage pN2 in 22.1% of the cases, and pN3 in 33.7% (in group II—73.4%, 19.5% and 7.1%, respectively), with a presence of extracapsular infiltration in 68.4% patients (vs 41.7% in group II) and with a significantly higher percentage of micrometastatic nature in group II (17.0%, vs 3.2% in group I). The failure of intraoperative sentinel lymph node mapping indicates a significantly increased risk of breast cancer metastases to the axillary lymph system. At the same time, it can also indicate higher cancer stage and its increased aggressiveness. For this reason, in such situation performance of axillary lymph node dissection still appears to be the approach most advantageous for patients.     

超声定位下可疑淋巴结取样在早期乳腺癌手术中的临床研究

目的 探讨早期乳腺癌更为合理的腋窝淋巴结处理方法,明确腋窝可疑淋巴结取样结合前哨淋巴结活检(SLNB)替代单纯SLNB时的假阴性率是否明显降低,为临床应用提供依据.方法 采用传统的腋窝淋巴结外科学分群方法,对符合入组条件的42例早期乳腺癌患者术前行B超引导下钩丝定位,术中行腋窝SLNB和定位的可疑淋巴结活检,再行全腋窝...     

Factors Affecting Nodal Status in Invasive Breast Cancer: A Retrospective Analysis of 623 Patients

Abstract: With increasing numbers of early, screen‐detected breast cancers and the emergence of sentinel‐node biopsy, surgical management of the axilla is evolving. In recent years many authors have searched for favorable subcategories of tumors in which it may be possible to avoid axillary lymph node clearance. The aim of this study is to determine preoperative factors that might predict lymph node negative axillae. A retrospective analysis of 623 patients with invasive breast cancer was performed. A number of clinical and pathological variables were analyzed. Uni‐ and multivariate analysis was carried out to determine factors predictive for lymph node metastases. Age, tumor size, grade, histology and lymphovascular invasion were found to be independent predictors of nodal positivity but, contrary to other recent studies, we found no effect of ER/PR (estrogen‐receptor/progesterone‐receptor) or HER‐2 status. The strongest predictor of lymph node metastases was tumor size >50 mm (OR 2.33), followed by the presence of lymphovascular invasion (OR 1.33). Our results could be used for preoperative counseling and planning axillary surgery in patients with invasive breast cancer. We propose that the predictive factors identified in this study could be used in combination with axillary ultrasound to selectively target patients for sentinel‐node biopsy or to target the use of ultrasonographic assessment of the axilla. However, no consistent and reliable markers have been identified to predict patients that can safely avoid axillary surgery.     

Axillary Lymph Node Echo-Guided Fine-Needle Aspiration Cytology Enables Breast Cancer Patients to Avoid a Sentinel Lymph Node Biopsy. Preliminary Experience and a Review of the Literature

Purpose For many years, the status of the axillary lymph nodes has been determined by an axillary lymphadenectomy. However, a sentinel lymph node biopsy has been shown to effectively replace the need for an axillary lymphadenectomy in order to determine the axillary staging. This study presents the preliminary results regarding the efficacy of fine-needle aspiration cytology (FNAC) to identify metastatic axillary lymph nodes in the pre-operative phase. Methods One hundred lymph nodes from 100 patients with histologically and cytologically confirmed breast cancer (cT1–2 cN0) underwent echo-guided FNAC. The diagnostic accuracy (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV]) for the axillary metastases was evaluated based on the histological findings of either a sentinel lymph node biopsy or an axillary lymphadenectomy as a reference standard. Results It was possible to avoid a sentinel lymph node biopsy in 30% of the cases; the sensitivity was 68%, specificity 100%, PPV 100%, and NPV 65%. Echo-guided FNAC of the axillary lymph nodes should thus be included among the regular diagnostic procedures of presurgical staging. Conclusion This simple, inexpensive, and minimally invasive technique makes it possible to avoid the additional cost of a sentinel lymph node biopsy while also sparing the patient the stress of undergoing a second surgery.     

Experience of sentinel node biopsy alone in early breast cancer without further axillary dissection in patients with negative sentinel node

AIMS: The aims of surgical therapy of breast cancer are loco-regional tumour control and staging. Axillary staging is still considered the single most important prognostic indicator in breast cancer. Surgical removal of axillary nodes remains the standard way to assess their involvement in most centres. The morbidity associated with axillary dissection (AD) is well recognized. In recent years sentinel node biopsy (SNB) has evolved. Multiple studies suggest it has the same accuracy as AD in axillary staging and less morbidity in early breast cancer (EBC). SNB has become the standard of practice in EBC in many parts of the world. In Australia, the preference has been to wait for the results of the Sentinel Node versus Axillary Clearance (SNAC) trial as well as other international trials before accepting SNB as a standard of care. The experience of a single surgeon with SNB alone in EBC without further completion axillary dissection (CAD) in negative sentinel node (SLN) is described in the present paper. METHODS: An audit was done of the senior author's prospective data from the Royal Australasian College of Surgeons database. Other information was added retrospectively from case notes. RESULTS: Between December 2000 and December 2003, 154 EBC cases (153 patients) underwent SNB alone. An average of four SLN was removed. Of these cases, 31.8% had positive SLNs (excluding 2.6% cases that had isolated tumour cells), of these, 93.9% had metastases (39.1% micro- and 60.9% macro-metastases) in axillary-SLN (ASLN) and almost all of these had CAD. ASLNs were the only positive nodes in 73.9%. Extra-ASLN retrieved in 68.8% of 34% demonstrated on lymphoscintigraphy. Of these, 12.1% were positive (6.1% micro- and macro-metastases each), all internal mammary. Mean follow up was 22.1 months. There was one local-regional-systemic and one systemic recurrence over this time. CONCLUSION: SNB has a valid role in staging of the axilla particularly in low-risk patients. After adequate self audit, SNB offers a minimal morbidity and reliable method of axillary staging. Patients choosing SNB alone must understand that the long-term results of the randomized controlled trial are still pending for level I evidence of long-term efficacy.     

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. ▪     

Failure to harvest sentinel lymph nodes identified by preoperative lymphoscintigraphy in breast cancer patients

Abstract: Selective sentinel lymphadenectomy dissection has been demonstrated to have high predictive value for axillary staging in breast cancer patients. Preoperative lymphoscintigraphy can localize and facilitate the harvesting of sentinel lymph nodes (SNLs) with a high success rate. The failure rate of selective sentinel lymphodenectomy ranges between 2% and 8%. Details of the failures were seldom addressed. This study analyzes the causes of failure to harvest SLNs in spite of positive preoperative lymphoscintigraphy. From November 1997 through November 2000, 201 female patients with histologically confirmed and operable breast carcinoma underwent selective sentinel lymphadenectomy at the University of California, San Francisco (UCSF) Carol Franc Buck Breast Care Center. Among these patients, 183 (91%) received preoperative lymphoscintigraphy to identify axillary lymph nodes. The causes of failure to harvest the SLNs in this group of patients despite successful preoperative lymphoscintigraphy were analyzed. In our series, the failure rate of SLN identification was 7.0% (14/201). The failure rate for our first year was 11.1% (6/54), second year 9.1% (7/77), and third year 1.4% (1/70). The incidence of failure in spite of positive preoperative lymphoscintigraphy was 3.5% (6/170). The shine-through effect of the primary injection site and failure to visualize a blue lymph node were the main reasons for technical failure. Most of these cases occurred during our learning curve of the procedure. The possibility of failure to get the SLN should be explained to patients before surgery. Axillary lymph node dissection (ALND) should be done if selective SLN dissection is not successful.      

Lymphatic Mapping of the Breast: Locating the Sentinel Lymph Nodes

When the concept of sentinel lymph node biopsy was described in patients with melanoma, researchers quickly started to use lymphatic mapping techniques in breast cancer patients in an attempt to locate the sentinel node in the axilla. We have been performing mammary lymphoscintigraphy in this role for 6 years and have now studied 159 patients. Like others, we have found that most breast cancers (93%) have lymphatic drainage that includes the axilla, and we have found an average of 1.4 axillary sentinel nodes in these patients. Surgical biopsy of the axillary sentinel nodes accurately staged the node field in 96% of patients. We have also found, however, that the pattern of lymphatic drainage from the cancer site is unpredictable; and in 49% of patients lymphatic drainage occurred across the center line of the breast to axillary or internal mammary sentinel nodes. In more than half of our patients (56%) lymphatic drainage occurred to lymph nodes outside the axilla including the internal mammary (45%), supraclavicular (13%), and interpectoral and intramammary interval nodes (12%). These nodes are also sentinel nodes, and their presence indicates that a sentinel node biopsy procedure that stages only the status of the axillary lymph nodes has the potential to understage about half the patients with breast cancer. High quality lymphoscintigraphy allows accurate mapping of peritumoral lymphatic drainage in most patients with breast cancer. It is possible that in the future accurate nodal staging in each individual will involve biopsy of all sentinel lymph nodes, regardless of their location.     

Contralateral axillary sentinel lymph node in breast cancer recurrence

The rare but significant reports of aberrant lymph node drainage outside of the ipsilateral axilla in patients with breast cancer necessitate a review of the staging and treatment strategies for these patients. Current staging modalities continue to describe this phenomenon as a stage IV cancer, which could have profound implications for clinical management. We report a case of a patient with recurrent right breast invasive ductal carcinoma whose preoperative lymphoscintigraphy revealed sentinel lymph node drainage to the contralateral axilla. This discovery subsequently altered surgical planning and her ultimate stage.     

Ratio of positive to total number of sentinel nodes predicts nonsentinel node status in breast cancer patients

Selective sentinel lymphadenectomy (SSL) has replaced axillary lymph node dissection (ALND) for many patients with early breast cancer and negative sentinel lymph nodes (SLNs). Yet many patients with a positive SLN are undergoing unnecessary ALND, as no further disease is found in the axilla. The aim of our study was to determine factors associated with additional positive lymph nodes in the axilla in patients who have a positive SLN. This was a retrospective study of patients undergoing SSL with ALND as part of their treatment for breast cancer at a single institution from November 1997 to August 2003. Only patients with one or more positive SLNs were selected for this study. There were 86 patients who fit our study criteria. Of these, 38% had further positive lymph nodes upon ALND. More than one positive SLN and a ratio of positive SLNs to total SLNs of greater than 0.5 were found to be predictors for additional axillary nodal involvement in both univariate and multivariate analyses. The number of positive SLNs and the ratio of positive SLNs to total SLNs is an indication of total tumor burden in the sentinel nodes and may be a reflection of the propensity of the tumor for further lymphatic invasion in the axillary basin.     

Preoperative Lymphoscintigraphy Predicts the Successful Identification but Is Not Necessary in Sentinel Lymph Nodes Biopsy in Breast Cancer

Background Although preoperative lymphoscintigraphy in sentinel lymph node biopsy (SLNB) for breast cancer patients is undergone commonly, its clinical significance remains controversial. Methods We retrospectively analyzed our database that contained 636 consecutive breast cancer patients who received preoperative lymphoscintigraphy before SLNB. Results The sentinel lymph nodes (SLNs) of 86.5% of patients were well imaged by lymphoscintigraphy, and SLN were located extra-axilla in 5.3% patients. The visualization of SLN in lymphoscintigraphy was not associated with histopathologic type, location, and stage of primary tumor, as well as the time interval from injection of radiocolloid to surgery. The negative lymphoscintigraphy results were associated with excision `biopsy before injection of radiocolloid and positive axillary node statues. The SLN was successfully detected in 625 (98.3%) enrolled patients. Failure of surgical identification of axillary SLN was associated with whether hot spot was imaged by lymphoscintigraphy. However, we identified axillary SLN in 90 (90.9%) out of 99 patients with negative axillary findings in lymphoscintigram. The false negative rate of SLNB in our study was 16.0% (15 of 94) among patients of training group, and there was no significant difference in the false negative rate between patients who had axillary hot spot in lymphoscintigram and those who had not (P = .273). Conclusions Visualization of SLN in preoperative lymphoscintigraphy predicted the successful SLN identification. However, it was less informative for the location of SLN during operation. Considering the complexity, time consumed, and cost, lymphoscintigraphy should at present be undergone for investigation purposes only.