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Sentinel Lymph Node Biopsy With Metastasis: Can Axillary Dissection Be Avoided in Some Patients With Breast Cancer?

From the Departments of Laboratory Medicine and Pathology, and Surgery, Mayo Clinic, Rochester, MN; and Departments of Biostatistics and Epidemiology, Surgery, Radiology, and Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA.

Address reprint requests to Carol Reynolds, MD, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St SW, Rochester, MN 55905; email reynolds.carol{at}mayo.edu

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
PURPOSE: Recent studies have suggested that the sentinel lymph node (SLN) biopsy is an accurate alternative staging procedure for women with breast cancer. The goal of this study was to identify a subset of breast cancer patients in whom metastatic disease was confined only to the SLN.

MATERIALS AND METHODS: From two institutions, we recruited 222 women with breast cancer for SLN biopsy. A SLN biopsy was performed in each patient, followed by an axillary dissection in 182 patients. Histologic and immunohistochemical cytokeratin stains were used on all SLNs.

RESULTS: The SLN was identified in 220 (97.8%) of the 225 biopsies. Evidence of metastatic breast cancer in the SLN was found in 60 (27.0%) of the 222 patients. Of these patients, 32 (53.3%) had evidence of tumor in the SLN only. By multivariate analysis, two factors were found to be significantly associated with a higher likelihood of tumor involvement in the non-SLNs: primary tumor size larger than 2.0 cm (P = .0004) and macrometastasis (> 2.0 mm) in the SLN (P = .002). Additional analysis revealed that none (0%; 95% confidence interval, 0% to 18.5%) of the 18 patients with primary tumors 2.0 cm and micrometastasis to the SLN had remaining axillary lymph node involvement.

CONCLUSION: The primary tumor size and metastasis size in the SLN are independent factors in predicting the incidence of tumor in the non-SLNs. Therefore, the SLN biopsy alone may be adequate for staging and/or therapy decision making in patients with primary breast tumors 2.0 cm and micrometastasis in the SLN.

	INTRODUCTION

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THE SENTINEL LYMPH node (SLN) is the first lymph node in a nodal basin to drain the primary tumor.¹ In theory, if the SLN does not contain metastatic cancer, the remainder of the nodal basin will be negative for metastases. Therefore, nodal dissection can be avoided in patients with negative SLN. In breast cancer, multiple studies have shown that the SLN is accurate in predicting the absence of nodal metastasis.^2-7 Furthermore, in 38% to 67% of cases with metastatic axillary nodes, the only positive lymph node will be the SLN.^1,2,6-10 The goal of this study was to identify a subset of breast cancer patients in whom metastatic disease is confined only to the SLN.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Patient Population
Two hundred twenty-two women from two institutions (105 women from the Mayo Clinic and 117 women from the University of Pennsylvania) who had breast cancer were invited to participate in institutional review board–approved protocols for SLN biopsy. Study candidates were patients undergoing axillary dissection at the Mayo Clinic from October 1997 to December 1998 and at the University of Pennsylvania from April 1997 to January 1999. The tumor-node-metastasis system of the American Joint Committee on Cancer was used to categorized the primary breast tumors.¹¹ All but 40 patients (six patients at the Mayo Clinic and 34 patients at the University of Pennsylvania) underwent SLN biopsy followed immediately by standard level I and level II axillary lymph node dissection (ALND).

Administration of Blue Dye and/or Radiotracer and Lymphoscintigraphy
Two different surgical approaches were used to identify the SLN. At the Mayo Clinic, all patients received intraoperative injections of 4 to 5 mL of 1% isosulfan blue (Lymphazurin; US Surgical Corp, Norwalk, CT) into the breast parenchyma adjacent to the primary tumor. For those patients who had undergone previous excisional biopsy, the blue dye was injected around the region adjacent to the excisional cavity. The breast was massaged for 5 to 10 minutes before a standard transverse axillary incision was made. The incision was deepened to the clavipectoral fascia, which was divided. The axillary tissue at the caudad end of the incision was spread with a fine clamp. Initially, a limited axillary incision and dissection was performed to identify the blue-green lymphatic channel connecting to the SLN. One, and rarely two to five, blue-stained SLN was identified in the axilla. After identification and excision of the SLN, a level I and level II ALND was completed and submitted separately from the SLN biopsy for histopathologic examination. Six patients refused an axillary dissection; therefore, complete axillary dissection was not performed. Three patients had a T1b tumor, two patients had a T1c tumor, and one patient had a T2 tumor. In each case, one to three SLNs were identified and all were negative for tumor.

At the University of Pennsylvania, all patients underwent lymphoscintigraphy on the day of surgery. For patients with palpable breast tumors, 1 mCi of radiolabeled tracer, either technetium-99m sulfur colloid or technetium-99m human serum albumin, was injected in 6-mL volumes around the primary tumor. For patients with nonpalpable breast tumors or those who had previous excisional biopsy, the radiotracers were injected outside the biopsy cavity under ultrasound guidance at the Breast Imaging Center, University of Pennsylvania. Patients were then imaged using a large field of view gamma camera with a high-resolution collimator (Model 2000; General Electric Medical Systems, Milwaukee, WI). Dynamic images were taken after the injection of radiotracer for 1 to 2 hours. After localization of the tracer, anterior-posterior and lateral static images were taken to document the site of the radiographically identified draining lymph nodes. All such nodes were marked on the overlying skin with indelible ink. Patients were then transported to the operating room where 4 to 6 mL of 1% lymphazurin blue dye (US Surgical) was injected around the primary tumor site. An intraoperative gamma-detecting probe (US Surgical) was used to identify the SLN. An SLN was positively identified if it was blue or the lymph node had in vivo counts at least twice the background counts or ex vivo counts at least three times the background count of lymph nodes or fat. After removal of the SLN, the remainder of the level I and level II ALND was completed and submitted separately for histopathologic examination. An institutional review board–approved registration trial for SLN biopsy was recently instituted and 34 subsequent patients did not undergo axillary dissection because a complete axillary dissection was performed only when the SLN was positive.

Pathologic Evaluation
Lymph nodes were marked as sentinel or nonsentinel. A preliminary frozen section was performed on the SLN and non-SLNs at the Mayo Clinic. If the SLN was negative for tumor, the node was embedded in paraffin and at least four additional levels were examined with hematoxylin and eosin (H&E) and cytokeratin antibody (AE1/3, monoclonal antibody, 1/250; Boehringer Mannheim, Indianapolis, IN), together with a negative control. The non-SLNs were further evaluated with standard H&E-stained sections. The SLN and non-SLNs removed at the University of Pennsylvania were embedded in paraffin and stained with H&E and evaluated as above. In all cases, the size of the metastasis in the SLN was measured using an ocular micrometer. A micrometastasis was defined as a tumor deposit of 2.0 mm. Metastases larger than 2.0 mm were considered macrometastases. If multiple tumor deposits were present in the SLN, the sum of the tumor deposits was used to classify the metastasis as micro- or macrometastasis. In cases where more than one SLN was positive for tumor, the patient was grouped according to the largest size of metastasis. In patients with primary tumors 2.0 cm and micrometastasis to the SLN, three to eight levels including cytokeratin immunohistochemical analysis were performed on all non-SLNs. Primary tumors or re-excision specimens were examined by routine histology. Primary tumor size, histologic type, nuclear grade, mitotic count, the presence of lymphovascular invasion, margin status, and estrogen and progesterone receptors were determined.

Statistical Evaluation
Percentages and 95% exact confidence intervals (CIs) were used to estimate the relative frequency of cases with positive SLN. In the subset of cases with positive SLN, percentages and 95% exact CIs were again used to estimate the relative frequency of cases with positive non-SLNs. One patient with bilateral disease (primary tumor > 2.0 cm on both sides) and positive SLN with macrometastasis on both sides was found to have positive non-SLNs on the right side but negative non-SLNs on the left side. All statistical analyses were repeated with the patient included as having positive non-SLNs or as having negative non-SLNs. The results of these analyses showed negligible differences, thus the results in this article reflect the patient as having positive non-SLNs.

Fisher's exact test^12,13 was used to test for associations between the presence of positive non-SLNs or the presence of micrometastasis in the SLN and other factors, such as age, histologic type, nuclear grade, primary tumor size, lymphovascular invasion, mitotic count, estrogen and progesterone receptor status, and size of the SLN metastasis. All reported P values are two-sided.

Logistic regression¹⁴ was used to construct a multivariable model of independent factors associated with the presence of positive non-SLNs. Forward stepwise regression was used for factor selection and, because of the modest number of patients in the analysis, only factors that exhibited univariate significance levels of .05 or lower were examined. The factors examined were binary and coded 0 or 1. For each factor in the model, the likelihood of positive non-SLNs was estimated by the odds ratio (OR) and 95% CI. Model-estimated probabilities of having positive non-SLNs were calculated (probability = 1/ [1 + exp(-logit)]) for patient subsets. All analyses were performed using StatXact-3 (Cytel Software, Cambridge, MA) or SPSS for Windows (SPSS Inc, Chicago, IL) statistical software.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Patient Population
Two hundred twenty-two women with breast cancer were recruited for SLN biopsy from two institutions (Table 1). A total of 228 primary breast tumors were identified; three patients had bilateral tumors and three patients had two tumors within the same breast. Of the 228 primary tumors, 178 were T1 ( 2.0 cm), 47 were T2 (> 2.0 cm to 5.0 cm), and three were T3 tumors (> 5.0 cm; Table 1).

Sentinel Node Identification
A total of 225 SLN biopsies were performed (Table 1). An SLN was identified in 220 (97.8%) of the 225 biopsies. The predictive accuracy of SLN biopsy was 97.3%, determined in 182 patients in which a complete ALND was performed. Metastatic tumor was identified in the SLN biopsies of 60 patients, and the goal of this study was to further characterize this group of patients.

Histopathologic Results
Evidence of metastatic breast cancer in the SLN was identified in 60 (27.0%) of the 222 patients. Of these patients, 32 (53.3%) had evidence of tumor in the SLN only. Tumor was identified in the SLN by routine H&E-stained sections in 53 patients (88.3%). Seven patients had SLN biopsy specimens initially diagnosed as negative by standard H&E sections, which showed involvement by tumor after additional H&E levels or immunohistochemistry was performed. A micrometastasis was identified in each case. Five patients had primary tumors 2.0 cm or smaller and two patients had primary tumors larger than 2.0 cm.

Incidence of Metastasis by Primary Tumor Size
The SLN had tumor in 20.2% of biopsy specimens associated with primary breast tumors 2.0 cm (T1 tumor), and the incidence of metastases increased with primary tumor size: T1a = 4.3%, T1b = 19.5%, and T1c = 23.8%. For biopsy specimens associated with T2 and T3 tumors, 48.9% and 66.7%, respectively, had evidence of tumor in the SLN.

Relationship Between Clinicopathologic Features and Patients With Positive SLN Biopsy
Of the 60 patients with a positive SLN biopsy, 28 (46.7%) had tumor in the non-SLNs. Univariate tests of association between non-SLN status and various clinicopathologic features were analyzed (Table 2). Age, histologic type, nuclear grade, the presence of lymphovascular invasion, mitotic count, and progesterone receptor were not significantly associated with metastasis in the non-SLNs. Higher rates of tumor in the non-SLNs were associated with primary tumor size larger than 2.0 cm (P = .0001), macrometastasis (> 2.0 mm) in the SLN (P = .0008), and estrogen receptor negativity (P = .03). By stepwise regression, a multivariable logistic model was constructed, which indicated the increased likelihood of positive non-SLNs for patients with a primary tumor size larger than 2.0 cm (OR, 19.2; 95% CI, 3.7 to 99.2; P = .0004) and macrometastasis in the SLN (OR, 12.5; 95% CI, 2.4 to 63.6; P = .002). The logistic model took the form: logit = -2.76 + 2.95X₁ + 2.52X₂. X₁ and X₂ are binary variables for primary tumor size (0 = 2.0 cm and 1 = > 2.0 cm) and for size of metastasis in the SLN (0 = 2.0 mm and 1 = > 2.0 mm), respectively. Model-estimated probabilities of having positive non-SLNs were .06, .44, .55, and .94 for patients with primary tumors 2.0 cm or smaller and micrometastasis, primary tumors 2.0 cm or smaller and macrometastasis, primary tumors larger than 2.0 cm and micrometastasis, and primary tumors larger than 2.0 cm and macrometastasis, respectively.

Relationship Between Primary Tumor Size and Size of SLN Metastasis
To more closely examine the relationship of primary tumor size and the size of SLN metastasis to incidence of positive non-SLNs, we classified positive SLN patients by both features (Table 3). Eighteen patients (eight at the Mayo Clinic and 10 at the University of Pennsylvania) with primary tumors 2.0 cm or smaller had micrometastasis ( 2.0 mm) to the SLN, and none of these patients had metastasis to non-SLNs. An average of 2.5 SLNs (range, one to seven) were identified and 16 (76.2%) of the 21 SLN micrometastases were detected by H&E alone (Table 4). A total of 328 non-SLNs (average, 18.2; range, 10 to 31) were examined at three to eight levels together with immunohistochemical analysis using cytokeratin antibody. No additional tumor was identified in the non-SLNs in any of these patients. None of these patients had T1a tumors, five had T1b tumors, and 13 had T1c tumors. Nine (50.0%) of the 18 patients with primary tumors 2.0 cm or smaller and macrometastasis in the SLN (Table 3) had tumor in non-SLNs compared with those patients with primary tumors 2.0 cm or smaller with micrometastasis (P = .001). The tumor had also spread to other lymph nodes in six (66.7%) of the nine patients with primary tumors larger than 2.0 cm with SLN micrometastases compared with those patients with primary tumors 2.0 cm or smaller and micrometastasis (P = .0003). In patients with primary tumors larger than 2.0 cm and macrometastasis in the SLN, 13 (86.7%) of the 15 patients had a tumor in non-SLNs. Overall, a majority of the patients (79.2%) with primary tumors larger than 2.0 cm demonstrated metastases in non-SLNs independent of micrometastasis or macrometastasis in the SLN. Finally, neither primary tumor size nor other clinicopathologic features or combination of features was significantly associated with micrometastasis to the SLN (Table 5).

View this table: [in this window] [in a new window]   Table 4. Size of SLN Micrometastasis and Method of Identification of Metastasis in Patients With Primary Tumors 2.0 cm

	DISCUSSION

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The relationship between nodal metastases and primary tumor size is well established, with the histologic status of the axillary nodes as the single most important prognostic indicator of progression and survival in breast cancer patients.¹⁵ The increasing use of screening mammography over the past decade has dramatically changed the presentation of breast cancer with decreasing primary tumor size and lymph node positivity in patients with invasive breast cancer.¹⁶ Because of this, one of the most controversial issues with regard to breast cancer management is the role of the ALND in T1 tumors. The detection of axillary involvement by physical examination is inaccurate,^17,18 and even invasive breast tumors smaller than 1 cm have a risk of metastases that may approach 3% to 37%¹⁹; therefore, removal and histologic examination of the axillary lymph nodes has become the gold standard for determining whether lymph node metastases have occurred. However, ALND is a major operation and carries significant disadvantages, including cost, requirement of a general anesthetic, scarring, numbness, and occasional lymphedema.

Multiple studies have shown that the SLN can be identified in more than 90% of cases with greater than 95% accuracy in predicting the lymph node status of the axilla.^{1,3,4,6,10,20,21} The current study shows that the SLN was identified in 97.8% of patients with a 97.3% degree of accuracy in patients that underwent complete ALND. These data suggest that our performance of the SLN biopsy is an accurate reflection of the multiple studies published on the utility of this technique.^{1,3,4,10,20,21} Our study contained a significant proportion of patients with larger primary tumors (> 2.0 cm), and we found the identification and accuracy rates for performing SLN biopsy in these patients to be as reliable as in patients with small breast tumors (Bedrosian et al, manuscript submitted for publication). The type of technique used to identify the SLN, vital dye alone or preoperative lymphoscintigraphy, followed by intraoperative localization using a hand-held gamma probe and vital dye, seems equivalent in terms of identification rates and accuracy as reported by other studies.^1,4,5,10,22 However, both techniques have a learning curve because false-negative SLN biopsy specimens were found in five patients. Each occurrence was from a different surgeon early in their experience. Therefore, this technique should be rigorously tested by an individual surgeon before omitting the ALND and relying on SLN biopsy information only.

Numerous studies have shown that 38% to 67% of patients with breast cancer and positive SLNs have no other disease in non-SLNs.^1,2,6-10 In the current study, we sought to identify factors associated with predicting patients who have positive SLNs but were at a low risk of having disease in non-SLNs. Several researchers have looked at histologic or clinical features that would be useful for predicting which patients are at risk for having axillary metastases in early-stage breast carcinoma.^23-26 Our data demonstrated that the increasing size of the primary tumor and increasing size of the SLN metastasis were associated with non-SLN involvement by metastatic breast cancer. In one extreme, we found that 100% of patients with primary tumors larger than 3.0 cm and macrometastases in the SLNs had tumor involvement of non-SLNs (Bedrosian et al, manuscript submitted for publication), whereas in the other extreme, 100% of patients with primary tumors 2.0 cm or smaller (T1 tumors) with micrometastases in the SLNs had no evidence of tumor in the non-SLNs, despite rigorous examination of the non-SLNs by multiple H&E levels and cytokeratin immunohistochemical analysis. Moreover, 13 (72.2%) of the 18 patients in this group had T1c tumors and three patients had more than one SLN with metastatic tumor.

Several studies have concluded that patients with or without axillary micrometastases had no significant prognostic differences.^27-30 However, other studies have shown that patients with axillary micrometastases have a higher disease recurrence and lower overall survival than patients with tumor-free axillary nodes.^31-35 The prognostic significance of such nodal micrometastases is still uncertain,^31,36,37 and long-term follow-up data are needed to evaluate this issue. It is interesting to speculate about what role the size of the SLN metastasis may play in the development of other metastases. It is possible, given the data presented, that the SLN may serve as a source of metastasis to non-SLNs and other distant sites once a critical mass (> 2.0 mm) is achieved. Alternatively, the SLN may become infiltrated by tumor, thus causing other tumor emboli from the primary breast tumor to lodge in non-SLNs as well as distant sites. Whether there are any immunologic influences on the tumor in the SLN is unclear.

In light of the upcoming American College of Surgeons Oncology Group's trial, in which patients with invasive breast cancer and positive SLN will be randomized to complete ALND versus observation, the data from this study will provide useful information with respect to local control and odds of recurrence. We believe patients with small primary breast tumors and micrometastases in the SLNs will have extremely low rates of local recurrence, whereas those patients with primary breast tumors larger than 2.0 cm and macrometastases in the SLNs may be at higher risk for local failure despite adjuvant therapy. As the SLN technique becomes widely used as an alternative method of staging patients with breast cancer, it would seem advantageous to have pathologic data regarding the size of SLN metastasis to distinguish patients with a low risk from those patients with a high risk for axillary disease.

We propose that the completion ALND may not be necessary in women who have primary breast tumors 2.0 cm or smaller and micrometastasis in the SLN. This finding may have profound implications for clinical management of breast cancer, with greater emphasis placed on systemic treatment and a more individualized basis for surgical treatment. To determine whether removing only the SLN in the setting of micrometastatic disease impacts on survival will require long-term follow-up and randomized clinical trials.

	ACKNOWLEDGMENTS

 
We thank Tammy Distad for her expertise in data management at the Mayo Clinic, Rochester, MN, and the staff in Nuclear Medicine and the Breast Imaging Center at the University of Pennsylvania, Philadelphia, PA, for their assistance.

	REFERENCES

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Submitted November 18, 1998; accepted February 16, 1999.

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				K. Motomura, C. Egawa, Y. Komoike, S. Nagumo, H. Koyama, and H. Inaji Three-Axillary Lymph Node Sampling for the Prediction of Nonsentinel Node Metastases in Breast Cancer Patients With Sentinel Node Metastases Ann. Surg. Oncol., July 1, 2006; 13(7): 985 - 989. [Abstract] [Full Text] [PDF]

				G.-C. Hsu, C.-H. Ku, J.-C. Yu, C.-B. Hsieh, C.-P. Yu, and T.-Y. Chao Application of intraoperative ultrasound to nonsentinel node assessment in primary breast cancer. Clin. Cancer Res., June 15, 2006; 12(12): 3746 - 3753. [Abstract] [Full Text] [PDF]

				G. Houvenaeghel, C. Nos, H. Mignotte, J. M. Classe, S. Giard, P. Rouanet, F. P. Lorca, J. Jacquemier, and V. J. Bardou Micrometastases in Sentinel Lymph Node in a Multicentric Study: Predictive Factors of Nonsentinel Lymph Node Involvement--Groupe Des Chirurgiens De La Federation Des Centres De Lutte Contre Le Cancer J. Clin. Oncol., April 20, 2006; 24(12): 1814 - 1822. [Abstract] [Full Text] [PDF]

				H. D. Bear Sentinel Node Micrometastases and Non-Sentinel Nodes in Breast Cancer: How Much Do We Need to Know? J. Clin. Oncol., April 20, 2006; 24(12): 1788 - 1790. [Full Text] [PDF]

				M. Schaapveld, E. G. E. de Vries, W. T. A. van der Graaf, R. Otter, J. de Vries, and P. H. B. Willemse The Prognostic Effect of the Number of Histologically Examined Axillary Lymph Nodes in Breast Cancer: Stage Migration or Age Association? Ann. Surg. Oncol., April 1, 2006; 13(4): 465 - 474. [Abstract] [Full Text] [PDF]

				L. A. Lambert, G. D. Ayers, R. F. Hwang, K. K. Hunt, M. I. Ross, H. M. Kuerer, S. E. Singletary, G. V. Babiera, F. C. Ames, B. Feig, et al. Validation of a Breast Cancer Nomogram for Predicting Nonsentinel Lymph Node Metastases After a Positive Sentinel Node Biopsy Ann. Surg. Oncol., March 1, 2006; 13(3): 310 - 320. [Abstract] [Full Text] [PDF]

				G. Falconieri, S. Pizzolitto, and G. Gentile Comprehensive Examination of Sentinel Lymph Node in Breast Cancer: A Solution Without a Problem? International Journal of Surgical Pathology, January 1, 2006; 14(1): 1 - 8. [Abstract] [PDF]

				K.-A. Joseph, M. El-Tamer, I. Komenaka, A. Troxel, B. A. Ditkoff, and F. Schnabel Predictors of Nonsentinel Node Metastasis in Patients With Breast Cancer After Sentinel Node Metastasis Arch Surg, June 1, 2004; 139(6): 648 - 651. [Abstract] [Full Text] [PDF]

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				K. M. McMasters The Eternally Enigmatic Axilla: Further Controversy About Axillary Lymph Nodes in Breast Cancer Ann. Surg. Oncol., December 1, 2003; 10(10): 1128 - 1130. [Full Text] [PDF]

				K. J. Van Zee, D.-M. E. Manasseh, J. L. B. Bevilacqua, S. K. Boolbol, J. V. Fey, L. K. Tan, P. I. Borgen, H. S. Cody III, and M. W. Kattan A Nomogram for Predicting the Likelihood of Additional Nodal Metastases in Breast Cancer Patients With a Positive Sentinel Node Biopsy Ann. Surg. Oncol., December 1, 2003; 10(10): 1140 - 1151. [Abstract] [Full Text] [PDF]

				B. D. Badgwell, S. P. Povoski, S. F. Abdessalam, D. C. Young, W. B. Farrar, M. J. Walker, L. D. Yee, E. E. Zervos, W. E. Carson III, and W. E. Burak Jr Patterns of Recurrence After Sentinel Lymph Node Biopsy for Breast Cancer Ann. Surg. Oncol., May 1, 2003; 10(4): 376 - 380. [Abstract] [Full Text] [PDF]

				D. K. Blanchard, J. H. Donohue, C. Reynolds, and C. S. Grant Relapse and Morbidity in Patients Undergoing Sentinel Lymph Node Biopsy Alone or With Axillary Dissection for Breast Cancer Arch Surg, May 1, 2003; 138(5): 482 - 488. [Abstract] [Full Text] [PDF]

				R. F. Hwang, S. Krishnamurthy, K. K. Hunt, N. Mirza, F. C. Ames, B. Feig, H. M. Kuerer, S. E. Singletary, G. Babiera, F. Meric, et al. Clinicopathologic Factors Predicting Involvement of Nonsentinel Axillary Nodes in Women With Breast Cancer Ann. Surg. Oncol., April 1, 2003; 10(3): 248 - 254. [Abstract] [Full Text] [PDF]

				G Cserni Complete sectioning of axillary sentinel nodes in patients with breast cancer. Analysis of two different step sectioning and immunohistochemistry protocols in 246 patients J. Clin. Pathol., December 1, 2002; 55(12): 926 - 931. [Abstract] [Full Text] [PDF]

				M A den Bakker, A van Weeszenberg, A Y de Kanter, F H Beverdam, C Pritchard, T. H van der Kwast, and M Menke-Pluymers Non-sentinel lymph node involvement in patients with breast cancer and sentinel node micrometastasis; too early to abandon axillary clearance J. Clin. Pathol., December 1, 2002; 55(12): 932 - 935. [Abstract] [Full Text] [PDF]

				M P G Leers, R H M G Schoffelen, J G M Hoop, P H M H Theunissen, J W A Oosterhuis, H v. Bijl, A Rahmy, W Tan, and M Nap Multiparameter flow cytometry as a tool for the detection of micrometastatic tumour cells in the sentinel lymph node procedure of patients with breast cancer J. Clin. Pathol., May 1, 2002; 55(5): 359 - 366. [Abstract] [Full Text] [PDF]

				F. D. Rahusen, H. Torrenga, P. J. van Diest, R. Pijpers, E. van der Wall, J. Licht, and S. Meijer Predictive Factors for Metastatic Involvement of Nonsentinel Nodes in Patients With Breast Cancer Arch Surg, September 1, 2001; 136(9): 1059 - 1063. [Abstract] [Full Text] [PDF]

				S. L. Wong, M. J. Edwards, C. Chao, T. M. Tuttle, R. D. Noyes, C. Woo, P. B. Cerrito, K. M. McMasters, and for the University of Louisville Breast Cancer Sen Predicting the Status of the Nonsentinel Axillary Nodes: A Multicenter Study Arch Surg, May 1, 2001; 136(5): 563 - 568. [Abstract] [Full Text] [PDF]

				M. R. Weiser, L. L. Montgomery, L. K. Tan, B. Susnik, D. Y. H. Leung, P. I. Borgen, and H. S. Cody III Lymphovascular Invasion Enhances the Prediction of Non-Sentinel Node Metastases in Breast Cancer Patients With Positive Sentinel Nodes Ann. Surg. Oncol., March 1, 2001; 8(2): 145 - 149. [Abstract] [Full Text] [PDF]