Sentinel Lymph Node Biopsy for Management of Breast Cancer

Albert B Lowenfels, MD

Disclosures

November 18, 2003

Editorial Collaboration

Medscape &

Lymphatic mapping, a recent technique first developed for the management of melanoma, is based on the concept that information about the status of the entire lymphatic drainage from a tumor site could be obtained by identification and sampling of a "sentinel" node.[1] A 1994 report described the first use of sentinel lymph node biopsy (SLNB) in the management of breast cancer.[2] Since then, the procedure has rapidly been accepted and now is widely applied for staging of breast cancer.

A symposium on SLNB provided new information about the current role of this new procedure in the management of breast cancer. In his introductory remarks, Armando E. Giuliano, MD, FACS,[3] of Santa Monica, California, an originator of the use of SLNB for breast cancer, challenged panel members to answer several questions: What is the current role of SLNB in the overall management of breast cancer? What techniques have proven to be reliable? Are there any technical problems? Is axillary dissection necessary? If so, when should it be performed?

SLNB and Sentinel Lymph Node Dissection (SLND) for Breast Cancer: Current Status

Michael J. Edwards, MD, FACS,[4] of Little Rock, Arkansas, opened the discussion by reviewing the current status of SLNB. The goals for surgery are 3-fold: diagnosis, staging, and therapy. With respect to therapy, the ultimate goal is cure, but additional goals are to afford local and regional control, to increase survival, and, if necessary, to afford palliation. How can SLNB help achieve these goals?

SLND is performed after the diagnosis of breast cancer has been established by sampling or excision of the primary tumor, so its main role relates to staging. By sampling the sentinel node, we can immediately determine whether or not the primary breast cancer has spread outside the original area, and this information has tremendous value for prognosis and for determining the need for chemotherapy. The presence or absence of axillary nodes is a strong predictor of outcome and enormously helpful for selecting effective chemotherapy.

Technical factors are extremely important for both the pathologist and the surgeon. Formerly, pathologists would examine several nodes in a dissected axillary specimen, but only obtain a single section from each node. Now, the pathologist takes multiple sections from a single node, yielding results that are highly predictive of the presence or absence of axillary disease. In patients who have had both an SLNB and a complete axillary dissection, false-negative results are rare (< 5%) if the procedure is performed properly. But to achieve accurate results, the surgeon must be experienced. For surgeons who have performed less than 20 SLNB procedures, the false-negative rate is double the rate encountered by surgeons who have performed more than 20 procedures. Experience counts, as in every other area of surgery. Based on the excellent results obtainable when SLNB is performed in centers with experienced surgeons and pathologists, this procedure is likely to become the gold standard for determining axillary status. Decision analysis suggests that SLNB is the procedure of choice for breast tumors that are ≤ 4 cm in diameter.[5]

Dr. Edwards pointed out that the need for complete axillary dissection in patients with a positive sentinel node is questionable because there is little evidence that removing involved axillary nodes has any great survival benefit. At most, the impact of axillary dissection is likely to influence survival by only 3% to 5%.

Technical Considerations of SLNB: Current Controversies

One area of controversy concerns the correct method to detect the sentinel node, noted Monica Morrow, MD, FACS,[6] of Chicago, Illinois. Which is better: a dye or a radioactive tracer? Or, should both methods be used? In Dr. Morrow's opinion, it doesn't matter. Both methods are equally suitable for identifying the sentinel node, but blue dye identification alone is simpler, less expensive, and entirely suitable. It can be used effectively by surgeons who are learning the technique of SLNB.[7] Furthermore, where should the dye be injected: in and around the tumor, intradermally, or in the subareolar area? Again, it seems to make little difference, since lymphatic drainage from the breast nearly always goes through the sentinel node before flowing to other lymph nodes. Injecting the dye in the peritumor region is currently a popular method.

Another area of controversy concerns the selection of patients suitable for SLNB. Can it be performed in patients with multicentric breast cancer? Most of these tumors, even though they arise in different parts of the breast, drain to the same sentinel node, so that SLNB is acceptable. SLNB is also suitable for patients with ductal carcinoma in situ (DCIS), even though in this entity, axillary spread is uncommon.

What is the accuracy of SLNB in patients who have received neoadjuvant chemotherapy prior to surgery? Does preoperative chemotherapy affect the accuracy of this procedure? Dr. Morrow stated that SLNB might be less accurate after chemotherapy, although there are reports that SLNB is reliable even after preoperative chemotherapy.[8,9]

A final controversial point concerned the value of internal mammary node biopsy. Should it be done as a staging procedure? The rationale for adding this extra step is that it might improve overall staging accuracy. However, Dr. Morrow noted that only about 5% or less of breast cancer patients have isolated internal mammary node involvement. Thus, it is unlikely that sampling the internal mammary nodes would provide significant additional information about lymph node spread.

Is Axillary Staging Still Necessary?

Daniel F. Hayes, MD,[10] of Ann Arbor, Michigan, a medical oncologist, discussed the question of whether or not axillary staging is still necessary. Since removal of the axillary lymph nodes adds little to overall survival, its current role is simply to provide staging information. But perhaps detailed information about the primary tumor is sufficient to perform accurate staging. Although there are many prognostic factors available from the primary tumor, such as estrogen receptor status, Dr. Hayes believes that the presence or absence of axillary disease is still the most reliable way to stage breast cancer and gives the best information about survival. However, in some patients accurate staging may be unimportant. For example, chemotherapy is probably unnecessary for an 85-year-old woman with an estrogen-positive breast cancer, so why bother to look for axillary nodes?

Dr. Hayes also presented data showing that breast cancer mortality for women aged 50-69 years is decreasing. In his view, effective chemotherapy is the main reason for this gratifying result; however, other panel members disagreed, and attributed most of the decrease in mortality to more widespread use of mammography.

Blake Cady, MD, FACS,[11] of Providence, Rhode Island, also believes that breast cancer mortality is finally decreasing, probably attributable to earlier diagnosis. Currently in Rhode Island, only 26% of all breast cancer patients have positive axillary nodes, a decrease most likely to have been brought about by more widespread screening. On the basis of current data, only 25% of all breast cancer patients would receive any benefit from axillary node dissection. For patients who are SLNB negative, the false-negative rate is low. For example, Dr. Cady's group followed 206 SLNB-negative women for a median period of 26 months. During this interval, only 3 axillary recurrences occurred, giving a false-negative rate of 1.4%.[12]

With respect to the need for axillary dissection when the SLNB is positive, Dr. Cady pointed out that axillary dissection does not seem to have much impact on overall survival. Why is this? Presumably because when the axillary nodes are positive, there is an increased probability of distant metastatic spread. Thirty-six percent of all breast cancer patients have evidence of epithelial cancer cells in their bone marrow, which increases the risk of death from breast cancer by a factor of about 4.[13] The issue of the need for axillary dissection when SLNB is positive is currently unresolved, and awaits the results of the Z11 study, currently being conducted by the American College of Surgeons.

Summary

During the discussion period, several questions arose:

  • Is the surgeon obligated to offer SLNB? The panel concurred that SLNB is currently the procedure of choice, and may be the "gold standard" for staging, but that there are important training issues. Many surgeons are not familiar with the procedure, and if they perform SLNB, they may be unable to locate the correct node.

  • Several surgeons asked about the advisability of axillary dissection if the SLNB is positive. In this situation, most surgeons are performing axillary node dissection, even though the evidence for any benefit is inconclusive.

  • Can lymphedema occur after SLNB? Yes, but predictably it is much less common than after standard axillary dissection.[14]

  • How much radioactive tracer is necessary to identify the sentinel node? The dose is tiny. One panelist suggested 0.5 millicuries, which is much less than the 20 millicuries required for a bone scan.

In summary, all participants in this symposium believed that SLNB is now the procedure of choice for determining axillary status, but that for accurate results, the surgeon must be experienced in identifying the correct node, and the pathologist must carefully examine the resected specimen. The issue of whether or not a complete axillary dissection should be performed when the SLNB is positive remains unresolved, but SLNB clearly provides valuable staging information with less morbidity than a standard axillary dissection. In the future, the same information currently supplied by SLNB may be obtained solely by sophisticated multigene analysis of the primary breast cancer.

References
  1. Tanis PJ, Nieweg OE, Valdes Olmos RA, Rutgers EJ, Kroon BB. History of sentinel node and validation of the technique. Breast Cancer Res. 2001;3:109-112. Abstract

  2. Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994;220:391-398. Abstract

  3. Giuliano AE. Sentinel lymph node biopsy for breast cancer. Program and abstracts of the American College of Surgeons 89th Clinical Congress; October 19-23, 2003; Chicago, Illinois.

  4. Edwards MJ. Current status of sentinel lymph node biopsy for breast cancer. Program and abstracts of the American College of Surgeons 89th Clinical Congress; October 19-23, 2003; Chicago, Illinois.

  5. Wong SL, Abell TD, Chao C, Edwards MJ, McMasters KM. Optimal use of sentinel lymph node biopsy versus axillary lymph node dissection in patients with breast carcinoma: a decision analysis. Cancer. 2002;95:478-487. Abstract

  6. Morrow M. Technical aspects and controversies: Sentinel lymph node biopsy for breast cancer. Program and abstracts of the American College of Surgeons 89th Clinical Congress; October 19-23, 2003; Chicago, Illinois.

  7. Morrow M, Rademaker AW, Bethke KP, et al. Learning sentinel node biopsy: results of a prospective randomized trial of two techniques. Surgery. 1999;126:714-720. Abstract

  8. Mamounas EP. Sentinel lymph node biopsy after neoadjuvant systemic therapy. Surg Clin North Am. 2003;83:931-942. Abstract

  9. Julian TB, Dusi D, Wolmark N. Sentinel node biopsy after neoadjuvant chemotherapy for breast cancer. Am J Surg. 2002;184:315-317. Abstract

  10. Hayes DF. Do tumor features obviate the need for axillary staging? Program and abstracts of the American College of Surgeons 89th Clinical Congress; October 19-23, 2003; Chicago, Ilinois.

  11. Cady B. Is axillary dissection necessary? The management of the sentinel node-positive patient. Program and abstracts of the American College of Surgeons 89th Clinical Congress; October 19-23, 2003; Chicago, Ilinois.

  12. Chung MA, Steinhoff MM, Cady B. Clinical axillary recurrence in breast cancer patients after a negative sentinel node biopsy. Am J Surg. 2002;184:310-314. Abstract

  13. Braun S, Pantel K, Muller P, et al. Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N Engl J Med. 2000;342:525-533. Abstract

  14. Blanchard DK, Donohue JH, Reynolds C, Grant CS. Relapse and morbidity in patients undergoing sentinel lymph node biopsy alone or with axillary dissection for breast cancer. Arch Surg. 2003;138:482-487. Abstract

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