How Should The Results Of SNB Be Utilized In Clinical Practice?
Can Full Axillary Lymph Node Dissection (ALND) be Avoided in Patients With Negative Findings on Sentinel Lymph Node Biopsy (SNB)?
The reported test performance characteristics of SNB vary widely across studies reported in the medical literature. However, when carried out by an experienced team, negative findings appear to be predictive of negative axillary nodes for most patients with breast cancer. Significant predictors of posttest probability include the percentage of patients in the study population with positive axillary nodes and the proportion of successful lymphatic mappings. In addition, the incidence of axillary recurrence after negative findings on SNB is comparable to that following ALND. On the basis of the available evidence, the Panel supports the use of SNB for staging disease in most women with clinically negative axillary lymph nodes. The concept of SNB has been so appealing to physicians and patients that the identification and biopsy of sentinel lymph nodes (SLNs) has largely replaced ALND for patients with clinically and histologically tumor-free lymph nodes. The Panel recommends that suspicious palpable nodes should also be submitted as SLNs, and that, in this context, the surgeon should have a low threshold for default to ALND, particularly for patients whose clinical presentation suggests a high risk of axillary metastasis. SNB works well, with a comparable false-negative rate in the setting of both mastectomy and breast-conserving surgery. Nevertheless, the Panel concluded that, on the basis of the available literature, there are compelling reasons for the operating surgeon to default to ALND, including a failed or technically unsatisfactory SNB procedure, and the presence of clinically suspicious nodes in the axilla after the removal of all SLNs. About half of patients in whom the identified SLN proves to be falsely negative will have had clinically suspicious nodes palpable at surgery, because gross tumor involvement may interfere with the uptake of both radiolabeled colloid and dye and deviate lymph flow to a node other than the true SLN.
Is Full ALND Necessary for All Patients With Positive Findings on SNB?
The recently reported meta-analysis demonstrates that, among patients with a positive SLN, 48.3% (95% CI, 35 to 62) were found to have additional node disease on ALND. Thus, the Panel recommends routine ALND for patients with a positive SLN according to routine histopathologic examination. More problematic is the management of patients for whom the SLN is positive only with use of special studies, primarily immunohistochemical (IHC) analysis with antibodies to cytokeratin. IHC evaluation can upstage disease for approximately 10% of patients who have a negative SLN, but whether this conversion to a higher stage is relevant remains unknown at this time. In the new American Joint Cancer Commission (AJCC) staging system, the node classification (pN0) is not altered by clusters of isolated tumor cells of 0.2 mm or less, regardless of the staining technique used to identify them.
It remains unclear whether isolated tumor cells or micrometastases (lymph node metastases larger than 0.2 mm but not larger than 2 mm) detected with hematoxylin and eosin (H&E) staining or special stains represents an adverse prognostic indicator and whether ALND should be carried out in all such cases. Likewise, there are insufficient data to determine whether the presence of isolated tumor cells or micrometastases should be a factor in treatment decisions. However, metastasis is found in nonsentinel nodes in approximately 10% of patients with isolated tumor cells in the SLN and in 20% to 35% of patients with micrometastases in the SLN. Until further studies addressing the clinical relevance of isolated tumor cells or micrometastases in the SLN are complete, the Panel recommends routine ALND for patients with micrometastases (>0.2 <2mm) found on SNB, regardless of the method of detection. Regarding the question of which patients with a positive SLN may be appropriately treated with breast or axillary radiation and which patients should have completion ALND, relevant studies have included short follow-up and small numbers of patients in retrospective series, and no results from randomized controlled trials (RCTs) are available. Therefore, the Panel concluded that there are insufficient data to answer this question.
What Is the Role of SNB in Special Circumstances in Clinical Practice?
On the basis of the available literature, the Panel concluded that SNB is not recommended for large or locally advanced invasive breast cancers (T3 and T4); inflammatory breast cancer; ductal carcinoma in situ (DCIS), when breast-conserving surgery is to be done; pregnancy, in the setting of prior nononcologic breast surgery or axillary surgery; and in the presence of suspicious palpable axillary lymph nodes. Data are available to support the use of SNB for smaller tumors (T1 and T2); multicentric tumors; DCIS, when mastectomy or immediate reconstruction is planned; for older or obese patients; in male breast cancer; and prior excisional or diagnostic biopsy. The recommendations and levels of evidence are provided in the Table below.
Recommendations and Levels of Evidence
| Clinical Circumstance |
Recommendation for Use of Sentinel Node Biopsy |
Level of Evidence* |
| T1 or T2 tumors |
Acceptable |
Good |
| T3 or T4 tumors |
Not recommended |
Insufficient |
| Multicentric tumors |
Acceptable |
Limited |
| Inflammatory breast cancer |
Not recommended |
Insufficient |
| DCIS with mastectomy |
Acceptable |
Limited |
| DCIS without mastectomy |
Not recommended except for large DCIS (>5 cm) on core biopsy or with suspected or proven microinvasion |
Insufficient |
| Suspicious, palpable axillary nodes |
Not recommended |
Good |
| Older age |
Acceptable |
Limited |
| Obesity |
Acceptable |
Limited |
| Male breast cancer |
Acceptable |
Limited |
| Pregnancy |
Not recommended |
Insufficient |
| Evaluation of internal mammary lymph nodes |
Acceptable |
Limited |
| Prior diagnostic or excisional breast biopsy |
Acceptable |
Limited |
| Prior axillary surgery |
Not recommended |
Limited |
| Prior non-oncologic breast surgery (reduction or augmentation mammoplasty, breast reconstruction, etc) |
Not recommended |
Insufficient |
| After preoperative systemic therapy |
Not recommended |
Insufficient |
| Before preoperative systemic therapy |
Acceptable |
Limited |
Abbreviations: DCIS, ductal carcinoma-in-situ; SNB, sentinel lymph node biopsy; ALND, axillary lymph node dissection.
*Levels of Evidence: Good: Multiple studies of SNB test performance based on findings on completion ALND; Limited: Few studies of SNB test performance based on findings on completion ALND or multiple studies of mapping success without test performance assessed; Insufficient: No studies of SNB test performance based on findings on completion ALND and few if any studies of mapping success.
What Factors Affect the Success of SNB (Including Low Rates of Complications and False Negative Findings)?
The ability to evaluate individual or institutional accuracy with SNB on the basis of the proportion of successful mappings and the false-negative rate has enabled the procedure to gain widespread acceptance without prospective randomized trials. As SNB continues to replace ALND for staging of breast cancer, the Panel believes that appropriate training in the procedure and issues of quality control are very important. The strongest predictor of the false-negative rate across trials appears to be the proportion of patients for whom mapping is successful. In addition, the greatest proportion of successful mappings and the lowest false-negative rates were associated with studies in which both blue dye and radiolabeled colloid were used. While the Panel does not believe that American Society of Clinical Oncology (ASCO) should present separate guidelines for surgeons or institutions about the performance of this procedure, the Panel strongly supports the Guidelines for Performance of Sentinel Lymphadenectomy for Breast Cancer developed and updated in 2003 by the American Society of Breast Surgeons (http://www.breastsurgeons.org/officialstmts/sentinel.shtml). The American Society of Breast Surgeons recommends a rate of SLN identification of 85% with a false-negative rate of 5% or less in order to abandon axillary dissection. This Society maintains that performance of a minimum of 20 SNB procedures in combination with axillary dissection or with mentoring is necessary to minimize the risk of false-negative results. The Panel also recommends that surgeons (a) take a formal course on the technique, with didactic and hands-on training components; (b) have an experienced mentor; (c) keep track of individual results, including the proportion of successful mappings, false-negative rates, and complication rates; and (d) maintain follow-up on all patients over time. The Panel believes that these issues are important quality control measures as they could meaningfully impact on false-negative rates. While awaiting further results from RCTs, the Panel believes that high false-negative rates may have a direct adverse impact on patient care including accurate staging, treatment decision making, and long-term outcomes including survival. Clearly, the potential for both local as well as systemic undertreatment of patients increases as the false-negative rate increases. Case volume and experience are clearly important determinants of success, but there are insufficient data to recommend specific volume levels to maintain proficiency. However, the systematic review indicates that the proportion successfully mapped represents the strongest predictor of false-negative rate and may serve as a reasonable quality indicator for this procedure. In addition, the review demonstrates the anticipated reduction in the predictive value of a negative SNB with an increasing lymph node–positive rate in the population studied. Therefore, caution is required when applying the SNB procedure in patients at considerably increased risk for lymph node-positive disease.
Finally, the SNB procedure is very much a team effort with active skilled involvement of multiple disciplines including surgery, pathology, radiology, nuclear medicine, nursing, and pharmacy, among others. In addition to the individual training and experience required of all team members, optimal results with the SNB requires the integrated and highly coordinated effort that comes with experience and frequent application of the procedure. Importantly, pathologists evaluating SNB specimens should be trained and experienced in the detection of the minimal amount of disease that is characteristically found in SLNs (See Appendix 3 of original guideline document).
What Are the Potential Benefits and Harms of SNB?
The reported incidence of lymphedema following ALND varies widely and is dependent on many variables, including definition of lymphedema, the extent of surgery, use of radiation therapy, and length of follow-up, among others. SNB is thought to be associated with fewer complications such as infection (cellulitis) of the chest wall and arm, sensory changes, and lymphedema than conventional ALND. The Panel recommends that, as with any medical procedure, written informed consent be obtained from all patients before SNB. The benefits and harms of the procedure, including the potential for a false-negative result should be explained to the patient. Written patient educational materials should provide accurate information on the risk of complications, contraindications for the procedure, the need for a multidisciplinary team (surgeon, nuclear medicine technician, and pathologist), the potential costs (which may be offset by fewer complications and less follow-up care), the lack of long-term survival data, the risk of radiation exposure, and the follow-up protocols for each procedure. A comparison of the data in an understandable format will help to clarify some of the issues for patients making treatment choices.
