False Negative Rate of Sentinel Lymph Node Biopsy in Multicentric and Multifocal Breast Cancers May be Higher in Cases with Large Additive Tumor Burden

Abstract:  We aimed to evaluate the feasibility of sentinel lymph node biopsy (SLNB) in multicentric/ multifocal breast cancer. In this prospective study, 23 women with multicentric/multifocal breast cancer underwent SLNB at our institution from April 2002 to February 2006. Presence of preoperative axillary metastases was confirmed by FNA. Patients underwent sub-areolar radiopharmaceutical injection ± isosulfan blue to perform SLNB, then completion ALND. The false-negative (FN) rate of SLNB was determined based upon final pathology. Twenty women with multicentric and three with multifocal invasive carcinoma were enrolled. The SLN identification rate was 100%. The overall FN rate of SLNB was 15% (95% CI 0.0466, 0.4281). Both cases with FN SLNB had multicentric disease, pathologic stage III breast cancer and a larger tumor burden compared with the study population. SLNB using sub-areolar injection is feasible for patients with multicentric/multifocal breast cancer yet may be associated with a higher FN rate in patients with large additive tumor burden.     

Axillary Lymph Node Status in Multicentric Breast Tumors and Breast Tumors with Nipple Involvement

Background

Axillary lymph node dissection plays an important role in breast cancer management in terms of staging, prediction of prognosis, determination of adjuvant therapy, and local control of the primary tumor. The objective of this study was to evaluate the axillary lymph node involvement in multicentric breast tumors and breast tumors with nipple involvement in comparison with unifocal tumors.

Patients and Methods

We reviewed the records of 267 patients with stage I or IIA disease. The rates of axillary lymph node metastasis (ALNM) in patients with unifocal tumors, multicentric tumors, or nipple involvement were compared.

Results

209 (78%) patients had unifocal tumors, 24 (8%) had multicentric tumors, and 34 (12%) had nipple involvement. The incidence of ALNM was 9.76% in patients with unifocal tumors, 24.84% in patients with multicentric tumors, and 36.71% in patients with nipple involvement. Hence, the incidence of ALNM was significantly higher in patients with nipple involvement or multicentric tumors than in patients with unifocal tumors.

Conclusion

Our data suggest that compared to unifocal tumors, breast tumors with nipple involvement or multiple foci show a significantly higher incidence of ALNM which is a predictor of a poor prognosis.     

乳腺癌腋窝淋巴结解剖术(附169例分析)

目的总结乳腺癌腋窝淋巴结解剖术(axillary lymph node dissection,ALND)的手术方法和经验。方法回顾性分析原发性乳腺癌行ALND的169例临床资料。结果本组163例行Ⅰ、Ⅱ平面解剖术,6例行Ⅰ～Ⅲ平面解剖术。切除标本共检出淋巴结4273枚;每例10～69枚,平均(25.28±10.23)枚。术后切口感染3例(1.78%),经引流治愈;患侧上肢水肿4例(2.37%),其中3例为切除Ⅲ平面淋巴结患者,1例为切除Ⅰ、Ⅱ平面淋巴结患者;腋窝淋巴漏1例(0.59%),为切除Ⅲ平面淋巴结病例;患侧上臂内侧及背侧皮肤麻木14例(8.28%),患侧胸肌萎缩5例(2.96%),多发生在先期诊治病例(1999年12月前)或切除Ⅲ平面淋巴结病例。结论ALND要求应用精细解剖技术,切除Ⅰ、Ⅱ平面淋巴结即可,人为扩大手术范围会增加特异性并发症发生率。     

Predictors to Assess Non‐Sentinel Lymph Node Status in Breast Cancer Patients with Sentinel Lymph Node Metastasis

Abstract: The next step of sentinel lymph node biopsy (SLNB) in breast cancer is to determine which patients need axillary lymph node dissection (ALND) following a positive SLNB. A prospective database of 239 patients who underwent SLNB followed by complete ALND at Keio University Hospital from January 2001 to June 2005 was reviewed. A total of 131 patients with one or more positive sentinel lymph nodes (SLNs) were further analyzed. A univariate analysis showed a significant correlation between non‐SLN involvement and lymphatic invasion, vascular invasion, number of tumor‐involved SLNs, radioactivity of SLNs, and size of SLN metastasis (p = 0.0002, p = 0.004, p = 0.006, p = 0.04, p = 0.03, respectively). By multivariate analysis, lymphatic invasion and the number of tumor‐involved SLNs remained significant predictors of non‐SLN involvement. In breast cancer patients with a positive SLN, lymphatic invasion and the number of tumor‐involved SLNs were both independent predictors of non‐SLN involvement.     

A Prediction Model for the Presence of Axillary Lymph Node Involvement in Women with Invasive Breast Cancer: A Focus on Older Women

Axillary lymph node (ALN) status at diagnosis is the most powerful prognostic indicator for patients with breast cancer. Our aim is to examine the contribution of variables that lead to ALN metastases in a large dataset with a high proportion of patients greater than 70 years old. Using the data from two multicenter prospective studies, a retrospective review was performed on 2,812 patients diagnosed with clinically node‐negative invasive breast cancer from 1996 to 2005 and who underwent ALN sampling. Univariate and multivariate logistic regression were used to identify variables that were strongly associated with axillary metastases, and an equation was developed to estimate risk of ALN metastases. Of the 2,812 patients with invasive breast cancer, 18% had ALN metastases at diagnosis. Based on univariate analysis, tumor size, lymphovascular invasion (LVI), tumor grade, age at diagnosis, menopausal status, race, tumor location, tumor type, and estrogen and progesterone receptor status were statistically significant. The relationship between age and involvement of axillary metastases was nonlinear. In multivariate analysis, LVI, tumor size and menopausal status were the most significant factors associated with ALN metastases. Age, however, was not a significant contributing factor for axillary metastases. Tumor size, LVI, and menopausal status are strongly associated with ALN metastases. We believe that age may have been a strong factor in previous analyses because there was not an adequate representation of women in older age groups and because of the violation of the assumption of linearity in their multivariate analyses.     

S-Classification of Sentinel Lymph Node Predicts Axillary Nonsentinel Lymph Node Status in Patients with Breast Cancer

Background One-half of breast cancer patients with positive sentinel lymph node (SN) have no further metastases in the axillary lymph node basin. The aim of the present study was to identify patients with positive SN who are unlikely to have further metastases in the axillary lymph node basin, using a new classification of SN, namely the S-classification. Methods Specimens of positive SN were subjected to a pathological review according to the previously published S-classification. S-stages of positive SN were correlated with the status of further metastases in the axillary lymph node basin after axillary lymph node dissection (ALND). Results Of 117 patients who underwent sentinel lymph node biopsy, 36 (30.8%) had a positive SN and were subjected to level I and II ALND. The occurrence of positive nonsentinel nodes was significantly related to the S-stage of SN. No patient with stage SI had additional metastases in the nonsentinel lymph nodes, while 14.3% of patients with SII stage disease and 60.9 % of patients with SIII disease had other non-SN that were metastatic. Conclusion S-stages of positive SN are highly predictive for axillary nonsentinel node status. Especially patients with SI sentinel node metastases appear to be at low risk for further nonsentinel node metastases.     

Predicting Axillary Nodal Positivity in 1,787 Patients with Invasive Breast Carcinoma

Abstract: Axillary lymph node status continues to be the single most important prognostic variable regarding breast cancer survival in spite of the development of numerous new tumor markers. All patients with invasive breast cancer who underwent axillary lymph node dissection as part of their treatment were stratified by the primary lesion's T category (TNM staging system) and whether or not the lesion was clinically palpable. Laboratory parameters and breast cancer specific survival were stratified by palpability and T category. Six hundred and forty-two of 1,787 (36%) axillary node dissections contained metastases. Overall, the probability of axillary node involvement was higher for all palpable lesions versus all nonpalpable lesions (42% versus 13%, p = 0.00001). Palpable lesions were less likely to be ER or PgR positive. They had a lower percentage of favorable histologic patterns, were less likely to be diploid, and were more likely to overexpress HER2/neu, have a high S-phase, exhibit high nuclear grade, and microscopically reveal lymphatic tumor emboli or vascular invasion. When tumors were stratified by size, the probability of nodal involvement was higher within each T category for palpable lesions when compared with nonpalpable lesions. The 10-year Kaplan-Meier survival for patients with palpable invasive breast cancer was 75% compared with 90% for patients with nonpalpable lesions (p = 0.00001). Palpability is a poor prognostic sign.     

腔镜腋窝淋巴结清扫与传统腋窝淋巴结清扫对保乳手术美容效果影响的比较

目的探讨腔镜腋窝淋巴结清扫在乳腺癌保乳手术中的美容效果。方法2007年1月-2009年12月保乳手术中行腔镜腋窝淋巴结清扫术29例（EALND组）,并与同期33例传统腋窝淋巴结清扫（CALND组）进行比较,根据调查问卷和术后6个月以上站立位乳房照片评价术后乳房的美容效果。结果EALND组无中转开放手术,未发生意外损伤、皮下气肿、脂肪栓塞等并发症。EALND组清扫腋窝淋巴结（18．2±5．9）枚,显著多于CALND组（14．9±3．6）枚（t=2．694,P=0．009）。平均随访时间49．2月（36—69个月）。EALND组主观满意度优良率89．7％（26／29）,明显高于CALND组69．7％（23／33;Z=-2．509,P=0．012）;EALND组美容效果客观评分优良率86．2％（25／29）,明显高于CALND组75．8％（25／33;Z=-2．295,P=0．022）。结论腔镜腋窝淋巴结清扫术不仅能够达到传统腋窝淋巴清扫的治疗效果,而且具有缩小手术切口、改善保乳手术后乳房美容效果等优点。     

Multifocal and Multicentric Breast Cancer is Associated with Increased Local Recurrence Regardless of Surgery Type

Multifocal and multicentric breast cancers have been correlated with poor prognostic factors and worse outcomes versus unifocal disease. We evaluated the impact of multifocal and multicentric disease versus case controls with unifocal disease, matching for age, grade, T‐, and N‐stage. A total of 110 patients with multifocal (n = 93) or multicentric (n = 17) disease and 263 matched case controls were identified with a median follow‐up of 53 months and 64 months, respectively. The actuarial local control rates for the multifocal/multicentric and unifocal group were 88% and 97%, respectively at both 5 and 10 years (p < 0.001). On multivariate analysis, multifocal/multicentric disease remained associated with higher local recurrence after controlling for other covariates including surgery type. The disease‐free survival rates in the multifocal/multicentric group at 5 and 10 years were 75% and 71%, respectively, versus 87% and 78% at 10 years (p = 0.01). On multivariate analysis, multifocal/multicentric disease was no longer associated with worse disease‐free survival. There was no difference in the cohorts in terms of regional control, overall survival, or cancer specific survival. Our findings suggest that multifocal/multicentric disease may be associated with worse outcomes versus unifocal disease regardless of type of surgery. This suggests a more biologically aggressive cancer and may be an important consideration when managing these patients. Further studies are needed to better understand the impact of multifocal/multicentric breast cancers on outcomes.     

Incidence of Lymph Node Metastasis and its Impact on Long-term Prognosis in Clinically Localized Prostate Cancer

Background: Pelvic lymph node dissection (PLND) is an important staging method for men with clinically localized prostate cancer. We report our experience with staging PLND and the impact of lymph node metastasis on long-term prognosis.
Methods: One hundred forty-eight consecutive patients who underwent staging PLND for clinically localized prostate cancer were retrospectively studied. Patients were evaluated for the presence and number of lymph node metastases, treatment (prostatectomy vs. radiotherapy), and endocrine therapy, and analyzed with respect to disease progression and survival. The mean follow-up period was 52.9 months (range, 2.3 to 165.8 months).
Results: Thirty-two patients (21.6%) had pelvic lymph node metastases, the incidence of which markedly decreased from 32.3% in 1982 to 1987 to 6.7% in 1994 to 1997. The intervals to disease progression and cancer death were significantly shorter in patients with positive lymph nodes ( P < 0.001). In stage D1 disease, patients who underwent a radical prostatectomy tended to be free of progression longer than those receiving radiotherapy or conservative therapy ( P = 0.0546). Other factors, such as early endocrine therapy, the extent of lymph node involvement and the Gleason score of the primary tumor did not predict disease progression or survival.
Conclusion: These data suggest a decreasing trend in the incidence of lymph node metastasis in the PSA era. Although longer disease-free intervals were observed in radical prostatectomy-treated patients, the impact of an aggressive approach to stage D1 disease awaits further studies.     

乳腺癌腋窝淋巴结B超检查特异性回顾性分析

目的 探讨各辅助检查方法对乳腺癌腋窝淋巴结转移的诊断价值。方法 对天津医科大学附属肿瘤医院2009年3月至2009年6月253例经手术病理证实乳腺癌病人术前B超与钼靶、MRI、PET-CT资料进行回顾性分析,比较灵敏度、特异度、阳性及阴性预测值和准确性。结果 B超（253例）灵敏度,特异度,阳性及阴性预测值,准确性为70.6%,87.4%,84.8%,75.0%和79.1%;钼靶（220例）为14.6%,100%,100%,53.9%和57.3%;MRI（27例）为50.0%,100%,100%,71.4%,77.8%;PET-CT（23例）为90.0%,92.3%,90.0%,92.3%,91.3%。B超与病理对照的Kappa值为0.581,与病理的一致性一般;高年资组B超医师的灵敏度、特异度、准确性为与低年资组比较差异有统计学意义（P＜0.05）。结论 判断乳腺癌腋窝淋巴结转移状况B超优于其他检查,而且超声检查者的经验影响诊断结果。     

Survival Outcomes in Node-Negative Breast Cancer Patients Evaluated With Complete Axillary Node Dissection Versus Sentinel Lymph Node Biopsy

Background Sentinel lymph node (SLN) biopsy combined with microstaging-associated immunohistochemical staining for cytokeratin more accurately assigns patients to their corresponding diagnostic stage. The purpose of this study was to compare the survival outcomes of node-negative patients who received an SLN biopsy with historical control data of node-negative patients who received routine complete axillary lymph node dissection (CALND) in the pre-SLN biopsy era. Methods Under institutional review board approval, 2458 node-negative invasive breast cancer patients between the ages of 25 and 94 years (mean, 60 years) were treated at our institution from January 1986 to May 2004. Of these 2458 patients, 604 (25%) were evaluated with CALND, whereas 1854 (75%) were evaluated with SLN biopsy. All were treated according to the current stage-specific guidelines. Kaplan-Meier graphs of overall survival and disease-free survival were constructed for each group of patients, and the two groups were compared by using the log-rank test. Results Overall survival and disease-free survival for the CALND and SLN biopsy groups did not differ significantly (P = .98). The average number of lymph nodes extracted in the pre-SLN biopsy group was 18, whereas the average number of SLNs extracted in the post-SLN biopsy group was 3. Conclusions The survival rate among node-negative breast cancer patients who received an SLN biopsy alone has proven to have no significant difference (P = .98) from the survival rate among node-negative patients who received a CALND. SLN biopsy alone should replace CALND as the primary tool for axillary staging of breast cancer in node-negative patients.     

A Novel Segment Classification for Multifocal and Multicentric Breast Cancer to Facilitate Breast‐Conservation Treatment

Breast conservation treatment (BCT) is an appropriate alternative to mastectomy for the treatment of unifocal breast cancer. Multifocal and multicentric breast cancers (MFMCBC) challenge conventional indications for BCT and are often treated with mastectomy. Following progress in treatment strategies for unifocal tumors, there was a movement to evaluate the use of BCT for MFMCBC. Now a growing body of evidence from retrospective data has emerged, demonstrating acceptable local control and overall survival rates with BCT for MFMCBC. Prospective studies are needed to confirm these findings. One of the possible barriers to such trials is the absence of a standardized classification and nomenclature for MFMCBC at this point in time. A novel segment classification is presented in this article in an endeavor to overcome this deficiency and allow future work on this issue.     

Sentinel Node Biopsy Before Neoadjuvant Chemotherapy for Determining Axillary Status and Treatment Prognosis in Locally Advanced Breast Cancer

Background Treatment of locally advanced breast cancer with neoadjuvant chemotherapy assesses an in vivo tumor response while increasing breast conservation. Axillary clearance of nodal disease after treatment defines prognostic stratification. Our study objective was to show that sentinel node staging before treatment can optimize posttreatment prognostic stratification in clinically N0 patients. Methods Eighty-nine patients with locally advanced breast cancer were treated with neoadjuvant chemotherapy. Of these, 42 (47%) clinically palpable or image-detected nodes (cN+) were histologically confirmed before treatment (group 1), and 47 (53%) patients without palpable lymph nodes (cN0) had a sentinel lymph node (SLN) biopsy before treatment (group 2). Survival analysis was conducted with the Kaplan-Meier method. Results In groups 1 and 2, 82 (92%) of 89 patients had node-positive disease before treatment. Seven (8%) of 89 had negative SLNs and no completion axillary lymph node dissection, 24 (27%) patients had a complete pathologic axillary response (pCR^AX; 11 [26%] of 42 in group 1 and 13 [33%] of 40 in group 2), and 58 (65%) of 89 had residual disease in the axilla. Breast-conserving therapy was applied to 27 (30%) of 89 patients. The seven SLN-negative patients had no axillary recurrence at 25 months, and pCR^AX patients had a significantly higher overall survival than patients with residual disease. Conclusions This study validates the prognostic stratification of patients with a complete pathologic axillary response to neoadjuvant chemotherapy. The addition of SLN biopsy to cN0 patients before treatment increased accurate nodal staging by 53%, eliminated completion axillary lymph node dissection in 15%, and demonstrated an improved prognosis in 28% of pCR^AX patients. SLN biopsy before treatment provides accurate staging of cN0 patients; allows acquisition of standard treatment markers, prognostic biomarkers, and microarray analysis; and affords prognostic stratification after treatment.     

染料法前哨淋巴结活检治疗乳腺癌进展

本旨在复习前哨淋巴结活检术的发展过程和乳腺的淋巴引流解剖，总结染料法前哨淋巴结活检术在乳腺癌诊治中的临床意义。乳腺癌的淋巴转移常常首先到达腋窝前哨淋巴结，染料法前哨淋巴结活检术对腋窝淋巴结是否受累以及是否需行清扫有确切指导作用。当染料法前哨淋巴结活检阴性时，可不必常规行腋窝淋巴结清扫术，由此可避免后带来的并发症和痛苦。     

Second Biopsy of Axillary Sentinel Lymph Node for Reappearing Breast Cancer After Previous Sentinel Lymph Node Biopsy

Background Sentinel lymph node biopsy (SLNB) is a safe and accurate axillary staging procedure for patients with primary operable breast cancer. An increasing proportion of these patients undergo breast-conserving surgery, and 5% to 15% will develop local relapses that necessitate reoperation. Although a previous SLNB is often considered a contraindication for a subsequent SLNB, few data support this concern. Methods Between January 2000 and June 2004, 79 patients who were previously treated at our institution with breast-conserving surgery and who had a negative SLNB for early breast cancer developed, during follow-up, local recurrence that was amenable to reoperation. Eighteen of these patients were offered a second SLNB because of a clinically negative axillary status an average of 26.1 months after the primary event. Results In all 18 patients (7 with ductal carcinoma-in-situ and 11 with invasive recurrences), preoperative lymphoscintigraphy showed an axillary sentinel lymph node, with a preoperative identification rate of 100%, and 1 or more SLNs (an average of 1.3 per patient) were surgically removed. Sentinel lymph node metastases were detected in two patients with invasive recurrence, and a complete axillary dissection followed. At a median follow up of 12.7 months, no axillary recurrences have occurred in patients who did not undergo axillary dissection. Conclusions Second SLNB after previous SLNB is technically feasible and likely effective in selected breast cancer patients. A larger population and longer follow-up are necessary to confirm these preliminary data.     

Chylous Leak: A Rare Complication after Axillary Lymph Node Dissection

The authors present a case of a chylous leak after axillary lymph node dissection. Although this case has been treated conservatively, the authors discuss different treatment approaches.