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Background: Performing a sentinel lymph node biopsy (SLNB) is the standard of care for axillary nodal staging in patients with invasive breast cancer and clinically negative nodes. The procedure provides valuable staging information with few complications when performed by experienced surgeons. However, variation in proficiency exists for this procedure, and a great amount of experience is required to master the technique, especially when faced with challenging cases. The purpose of this paper was to provide a troubleshooting guide for commonly encountered technical difficulties in SLNB, and offer potential solutions so that surgeons can improve their own technical performance from the collective knowledge of experienced specialists in the field., Methods: Information was obtained from a convenience sample of six experienced breast cancer specialists, each actively involved in training surgeons and residents/fellows in SLNB. Each surgeon responded to a structured interview in order to provide salient points of the SLNB procedure., Results: Four of the key opinion surgical specialists provided their perspective using technetium-99 m sulfur colloid, and two shared their experience using blue dye only. Distinct categories of commonly encountered problem scenarios were presented and agreed upon by the panel of surgeons. The responses to each of these scenarios were collected and organized into a troubleshooting guide., Discussion: We present a compilation of 'tips' organized as a troubleshooting guide to be used to guide surgeons of varying levels of experience when encountering technical difficulties with SLNB.

The ACOSOG Z11 trial is rapidly changing use of axillary dissection, but it is not known how generalizable the Z11 results are. This study compares characteristics of the Z11 patients with the larger group of sentinel node-positive patients and evaluates two previously described Louisville algorithms to determine whether they might still be useful to predict extent of axillary node involvement and guide management of the axilla. The Yale Breast Center database was queried to calculate the Louisville prediction points for patients with a positive sentinel node and to compare the predicted with actual results. Of 1215 sentinel node biopsies performed between 2004 and 2010, 282 (23%) had at least one positive node. Thirty-one per cent of these patients would have been eligible for Z11. This group had much less axillary node involvement than the 69 per cent who were ineligible. The Yale data confirmed the accuracy of the two Louisville models and showed that tumor size, number of positive sentinel nodes, and proportion of positive sentinel nodes were all significant predictors. However, these results were much more robust if at least three sentinel nodes had been removed. The Z11 patients were clearly a good risk group. The data validate the two Louisville models and suggest that the models may be useful to select patients to avoid axillary dissection, both among the currently Z11-eligible and -ineligible populations. A modified algorithm is proposed in which all patients with a positive sentinel node have at least three total nodes removed.

Background: Sentinel lymph node (SLN) biopsy in patients undergoing prophylactic mastectomy (PM) remains controversial. We sought to determine the incidence of finding occult cancer and the frequency of SLN positivity in patients undergoing contralateral PM., Methods: Medical records of patients undergoing bilateral mastectomy at our institution from 2003 to 2008 were reviewed (n = 115). Eight patients (6.9%) had known bilateral cancer; an additional eight patients (6.9%) underwent BPM for risk reduction. The remaining 99 patients who had ipsilateral breast cancer and underwent contralateral PM formed the cohort of interest for this study. Univariate and multivariate analyses to determine factors correlating with occult malignancy and SLN positivity in the PM specimen were performed using SPSS ver. 17 (SPSS Inc., Chicago, IL)., Results: The median patient age was 50 y, and median ipsilateral tumor size was 1.7 cm. Occult contralateral malignancy was found in eight (8.1%); of these, six (75.0%) had DCIS only. A positive SLN was found on the prophylactic side in 2 (2.0%) patients. Both had ipsilateral inflammatory cancer, and over 15 positive ipsilateral lymph nodes post-neoadjuvant chemotherapy. Ipsilateral inflammatory breast cancer was correlated with the finding of invasive cancer in the contralateral PM (P = 0.006), and both the finding of ipsilateral inflammatory breast cancer and number of positive lymph nodes correlated with the finding of a positive contralateral SLN., Conclusion: The incidence of occult malignancy in PM is low (2%). However, patients with ipsilateral inflammatory cancer are at high risk of contralateral malignancy; SLN biopsy on the prophylactic side in these patients may be warranted., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to determine factors associated with lymph node metastasis among hormonally-responsive breast cancer patients > or = 70 years old, and to develop and validate a clinical prediction rule to predict the risk of lymph node metastasis in this population., Summary Background Data: Nodal evaluation in elderly women with breast cancer remains controversial. The ability to predict which elderly patients may be node-negative may spare them the morbidity of lymph node evaluation., Methods: Hormone-receptor positive breast cancer patients > or = 70 years old who participated in a prospective multicenter trial were divided into a training set (n = 554) and a test set (n = 146). Univariate and multivariate analyses were conducted to determine factors predictive of final nodal status. A clinical prediction rule was developed on the training set, and validated in the independent test set., Results: Median patient age was 76; median tumor size was 1.4 cm. 15.9% and 16.2% were LN+ in the training and test sets, respectively. On univariate analysis, patient age, tumor size, palpability, grade, and lymphovascular invasion predicted lymph node status. On multivariate analysis, patient age, tumor size, and lymphovascular invasion remained significant. A prediction rule was created; patients were categorized into quartiles by predicted risk. 5.4% and 0% of patients in the lowest quartile were node positive in the training and test sets, respectively., Conclusion: Some elderly breast cancer patients at low likelihood of lymph node metastasis may be spared lymph node evaluation.

Purpose: An accurate, intraoperative sentinel lymph node (SLN) test could decrease delayed axillary dissections. Molecular tests may be more sensitive than current intraoperative tests but historically have not been rapid enough and have not been properly validated. We present the results from a large, prospective evaluation of the first rapid molecular SLN test, the Breast Lymph Node (BLN) Assay., Methods: A beta trial (n = 304) to determine the threshold levels of mammaglobin and cytokeratin 19 correlating with metastasis greater than 0.2 mm and a validation trial (n = 416) to validate the threshold cutoffs were conducted. Alternating portions from each SLN were processed for histology and the BLN Assay., Results: BLN Assay performance against extensive permanent-section histology verified by central pathology review was similar to that expected of standard permanent-section histology: sensitivity, 87.6%; specificity, 94.2%; positive predictive value, 86.2%; and negative predictive value (NPV), 94.9%. In 319 patients with both frozen-section hematoxylin and eosin results and BLN Assay results, the BLN Assay had higher sensitivity (95.6%) and NPV (98.2%) than frozen section (sensitivity, 85.6%; NPV, 94.5%). The assay can be performed in approximately 36 to 46 minutes for one to three nodes., Conclusion: The BLN Assay allows a rapid evaluation of 50% of each SLN. Comparison with permanent-section histology on adjacent node pieces evaluated by expert pathologists indicated that the BLN Assay was more sensitive than current intraoperative techniques while maintaining high specificity. These data indicate that the assay may be clinically useful for intraoperative or postoperative axillary lymph node dissection decisions.

Background: Although the sentinel lymph node (SLN) is defined as the first node draining a tumor, multiple nodes are often identified. Few SLNs are required for adequate staging; removal of more may be unnecessary. The objective of this study was to determine factors influencing the number of SLN identified., Methods: The University of Louisville Breast Sentinel Lymph Node Study was used to determine correlates of identifying greater than 4 SLNs by using univariate and multivariate analyses., Results: An SLN was identified in 3,882 of 4,131 patients (94%). The median number of SLN identified was 2 (range 1-18); 90% had < or = 4 SLNs identified. Palpable tumors, surgeon inexperience, and dermal injection were associated with greater than 4 SLNs identified. All 3 of these factors remained significant on multivariate analysis., Conclusions: Palpable tumors often have greater than 4 SLNs identified, and the use of intradermal injection increases this probability.

Background: Preoperative evaluation of the axilla using fine-needle aspiration biopsy (FNAB) and/or intraoperative evaluation of the sentinel lymph nodes (SLNs) may significantly decrease the number of operative procedures required for staging or local control of the axilla in breast cancer patients. The purpose of this study was to examine and determine the number of operative procedures that could be excluded using both approaches., Methods: A retrospective review of data was performed on 168 patients presenting with invasive clinical stage 1 to 3 breast cancer from March 2004 to March 2007., Results: Of the 168 patients, 57 (34%) underwent ultrasound-guided FNAB for suspicious-appearing nodes. Of these 57 patients, 40 (70%) had a positive FNAB, and 16 (28%) had a negative FNAB. The FNAB was suspicious in 1 (2%) patient. One hundred twenty patients (71%) with a normal axillary ultrasound or with a negative or suspicious FNAB underwent SLN mapping, of which 29 (24%) had an intraoperative diagnosis of metastatic tumor., Conclusions: Preoperative evaluation of the axilla using ultrasound-guided fine-needle aspiration biopsy spared 24% of patients the cost and morbidity of undergoing SLN biopsy. SLN mapping, along with intraoperative evaluation of nodes, spared an additional 17% of patients from having to undergo a second operative procedure.

Hypothesis: It has recently been proposed that only 3 sentinel lymph nodes (SLNs) are required for an adequate SLN biopsy. Others have advocated removing all nodes that are blue, hot, at the end of a blue lymphatic channel, or palpably suspicious or that have radioactive counts of 10% or greater of the most radioactive SLN. Our objective was to determine the false-negative rate (FNR) associated with limiting SLN biopsy to 3 nodes., Design: Multicenter prospective study., Setting: Both academic and private practice., Patients: A total of 4131 patients underwent SLN biopsy followed by completion axillary node dissection., Main Outcome Measure: The FNR associated with 3-node SLN biopsy., Results: Of the 4131 patients in this study, an SLN was identified in 3882 (94.0%). The median number of SLNs identified was 2; more than 3 SLNs were removed in 738 patients (17.9%). Of the patients in whom a SLN was identified, 1358 (35.0%) were node positive. The overall FNR in this study was 7.7%. In 89.7% of node-positive patients, a positive SLN was found in the first 3 SLNs removed. If SLN biopsy had been limited to the first 3 nodes, the FNR would be 10.3% (P = .005 compared with removing >3 SLNs). The FNR increased with the strategy of limiting SLN biopsy to fewer SLNs (P<.001)., Conclusion: Removing only 3 SLNs cannot be recommended, because it is associated with a substantially increased FNR.

Background: The purpose of this study was to create a model that predicts which breast cancer patients will have sentinel lymph node (SLN)-only metastasis., Methods: SLN-positive breast cancer patients (N = 1,253) were analyzed. Multivariate analysis was performed to identify factors predicting SLN-only disease; a prediction rule was created., Results: Median tumor size was 2 cm. The median number of SLNs removed was 2; the median number of positive SLNs was 1. Multivariate analysis found tumor size, number of positive SLN, and proportion of SLN positive were significant predictors of SLN-only disease (P < .001). A prediction rule with 1 point being given for >1 positive SLN, 1 point for >50% of SLN positive, and up to 4 points for tumor size (T1a = 1, T1b or T1c = 2, T2 = 3, and T3 = 4) was established. Ninety-five percent of patients with 1 point had SLN-only disease (P < .0001)., Conclusion: An integer-based model may predict SLN-only disease and may be useful in determining whether completion axillary lymph node dissection is required.

Sentinel node biopsy has become well accepted as a minimally invasive means of accurately staging the axilla in breast cancer patients. Patients with metastases in the sentinel node(s) have traditionally proceeded to completion of axillary node dissection, whereas patients who are node negative can be spared the morbidity of this procedure. Recently, there has been some debate as to what constitutes node-positive disease and whether patients with metastasis in the sentinel node(s) require completion axillary dissection. This review addresses the controversies regarding the management of sentinel node-positive breast cancer patients.

Objective: To better understand the factors associated with the well-established gender difference in survival for patients with melanoma., Summary Background Data: Gender is an important factor in patients with cutaneous melanoma. Male patients have a worse outcome when compared with females. The reasons for this difference are poorly understood., Methods: This prospective multi-institutional study included patients aged 18 to 70 years with melanomas > or =1.0 mm Breslow thickness. Wide excision and sentinel lymph node (SLN) biopsy was performed in all patients. Clinicopathologic factors, including gender, were assessed and correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS)., Results: A total of 3324 patients were included in the covariate analyses; 1829 patients had follow-up data available and were included in the survival analyses. Median follow-up was 30 months. On univariate analysis, men (n = 1906) were more likely than women to be older than 60 years (P < 0.0001), have thicker melanomas (P < 0.0001), have primary tumor regression (P = 0.0054), ulceration (P < 0.0001), and axial primary tumor location (P < 0.0001). On multivariate analysis, age (P = 0.0002), thickness (P < 0.0001), ulceration (P = 0.015), and location (P < 0.0001) remained significant in the model. There was no difference in the rate of SLN metastasis between men and women (P = 0.37) on multivariate analysis. When factors affecting survival were considered, the prognosis was worse for men as validated by lower DFS (P = 0.0005), DDFS (P < 0.0001), and OS (P < 0.0001)., Conclusions: Male gender is associated with a greater incidence of unfavorable primary tumor characteristics without an increased risk for nodal metastasis. Nonetheless, gender is an independent factor affecting survival.

Background: Sentinel lymph node (SLN) biopsy examination is an accepted method of staging breast cancer patients. SLN biopsy examination in patients with drainage to the internal mammary chain (IMC) nodes is controversial., Methods: A prospective study of SLN biopsy examination followed by axillary dissection was analyzed to determine how surgeons manage patients with IMC drainage and the rates of axillary SLN identification and positivity in these cases., Results: Lymphoscintigraphy was performed in 2196 (53.2%) of the 4131 patients in this study. IMC drainage was noted in 80 patients (3.6%). An axillary SLN was identified in 29 of the 40 patients with IMC drainage alone (72.5%). The rate of finding a positive axillary lymph node did not differ based on the lymphoscintigraphic pattern (P = .470)., Conclusions: Most surgeons do not perform IMC SLN biopsy procedures. Even when lymphoscintigraphy shows isolated drainage to IMC nodes, axillary SLNs usually are identified. Lymphoscintigraphy therefore has limited usefulness.

The sentinel lymph node (SLN) is the lymph node that represents the 'gate-keeper' of the lymphatic basin; it is the first node to receive lymphatic drainage from the site of the primary tumor. SLN biopsy is a staging procedure and should be considered as such; it is not meant to be a therapeutic operation. The SLN can be mapped and biopsied using tracer agents (e.g. radiolabelled colloid and/or vital blue dye), which are injected around the primary tumor site. Pathologic analysis of the SLN using a combination of serial sectioning of the node, standard hematoxylin and eosin staining, and immunohistochemistry decreases the false-negative rate compared with traditional nodal processing. SLN biopsy is associated with lower morbidity than full lymphadenectomy. The SLN technique accurately reflects the metastatic status of the regional lymph-node basin; recurrent nodal disease in the mapped basin is rare following a tumor-free SLN biopsy result. The objectives of this review are to provide a current and concise overview of the current literature on SLN biopsy and describe its role in clinical oncology.

Background: Although sentinel lymph node (SLN) biopsy is widely accepted as a minimally invasive method of nodal staging, failure to identify an SLN mandates a level I/II axillary node dissection. The purpose of this study was to elucidate factors that independently predict failure to identify an SLN., Methods: Using a large multicenter prospective study of SLN biopsy for patients with invasive breast cancer, we performed univariate and multivariate regression analyses to determine clinicopathologic factors predictive of failure to identify an SLN., Results: Of the total 4131 patients in the study, an SLN was not identified in 249 (6.0%). Tumor location (P = .409), biopsy type (P = .079), surgery type (P = .380), and histologic subtype (P = .999) were not significant predictors of failure to identify an SLN. On multivariate analysis, age greater than 60 years (OR = 1.469; 95% CI, 1.116-1.934, P = .006), nonpalpable tumors (OR = 0.639; 95% CI, 0.479-0.852, P = .002), injection technique with blue dye alone (OR = 0.389, 95% CI, 0.259-5.86, P < .001), and surgical experience of less than 10 SLN biopsy cases (OR = 1.886; 1.428-2.492, P < .001) were significant independent predictors of failure to identify an SLN. Optimal SLN biopsy technique using an intradermal and/or subareolar injection of radioactive colloid and blue dye can improve SLN identification rates regardless of patient and tumor characteristics., Conclusions: Patient age and tumor palpability significantly affect the ability to identify an SLN in patients with breast cancer. Optimal injection technique can significantly improve sentinel node identification rate regardless of these factors.

Sentinel lymph node biopsy, popularized in melanoma, has revolutionized the management of breast cancer. While the morbidity associated with axillary node dissection was once thought to be a requisite risk in order to appropriately stage the axilla, large validation studies have demonstrated that sentinel lymph node biopsy is a minimally invasive technique that can accurately predict nodal status. This technique has become an accepted practice in many centers, but there remain many controversies surrounding the technique itself, the pathologic evaluation of the sentinel node and the optimal management of patients with minimal nodal disease. The historic roots of this technique are discussed, along with the controversial issues surrounding the technique and the clinical trials that are currently ongoing.

Over the last few decades, there have been unprecedented advances in the multidisciplinary management of breast cancer. Surgical principles have shifted away from the Halstedian concept of radical surgery towards more cosmetic breast-conserving procedures, and advances have been made in terms of oncologic and plastic surgical techniques for those opting for mastectomy and reconstruction. Sentinel lymph node biopsy has revolutionized the evaluation of patients' nodal status and has become widely accepted as "state of the art." Medical oncology has made tremendous advances and is no longer relegated to the patients with metastatic disease. It is well accepted that chemotherapy may play a role even in patients with small tumors. Certainly the impact of neoadjuvant chemotherapy for downsizing tumors and making them amenable for breast conservation is also widely accepted. The advent of anthracyclines and, more recently, taxane-based regimens has had a substantial impact on the management of breast cancer. In addition, newer hormonal therapies such as the aromatase inhibitors have rivaled the classic cornerstone of tamoxifen. Radiation therapy has evolved from the era of cobalt-based therapy to newer, less morbid, techniques. In addition to advances in external beam radiation, the concept of accelerated partial breast irradiation and intraoperative radiation therapy is evolving and continues to be the focus of research endeavors. The unparalleled advances in the management of breast cancer in the fields of surgical, medical, and radiation oncology over the last half century continue today with ongoing research and clinical trials. As we enter the new millennium, breast cancer management will continue to evolve.