Overview Of The Sentinel Lymph Node Concept

In patients with breast cancer that has not yet obviously spread throughout the body, the presence or absence of tumor cells in the axillary (armpit) lymph nodes (LNs) is the most important predictor of future cancer recurrence and death. At the present time, the status of the axillary LNs is also an important consideration in deciding whether or not to recommend chemotherapy to patients.

The sentinel lymph node (SLN) concept was first applied to patients with melanoma, a type of skin cancer that can be cured if diagnosed early, but is deadly when the disease has spread beyond the primary tumor. The SLN concept proposed that the primary tumor drained into one or more "first" or "sentinel" LNs, and then drained secondarily into the remaining upstream regional LNs. In patients without obvious evidence of melanoma spread to the LNs, or to other parts of the body, the only means of detecting small deposits of tumor cells in the regional LNs, prior to the SLN concept, was to remove all of the regional LNs for the pathologist to study. In many patients, the regional LNs turned out to be free of tumor, but these patients were still placed at risk of developing the potential complications of major LN resection, including chronic swelling, discomfort, reduced mobility, and increased risk of infection.

Dr. Don Morton, then at UCLA, developed the SLN concept, and pursued elaborate LN mapping studies in animals in an effort to confirm the validity of the new concept. In 1991, Dr. Don Morton and colleagues reported on their early research on SLN mapping in animal models. They confirmed that SLN mapping could indeed reliably and accurately identify the first LN(s) that drained the primary tumor site, and that these SLN(s) could then be exhaustively analyzed for microscopic deposits of tumor cells. Because of time and cost constraints, pathologists are not able to thoroughly examine multiple slices of the many LNs removed during a traditional regional LN resection. However, the removal of only one or a few SLNs permits exceptionally fine assessment of the entire LN(s) by pathologists.

Subsequently, the SLN mapping procedure was refined by Dr. Morton and colleagues, and was then evaluated in human melanoma patients within the setting of a large international multi-institutional study. This study determined that SLN mapping could accurately stage the regional LNs of patients with melanoma, allowing the majority of patients with clinically early stage disease to avoid radical regional LN resection. Today, SLN mapping has become the standard-of-care approach to staging patients with melanoma in the absence of clinically apparent LN or distant disease.

In 1994, at the John Wayne Cancer Institute, Drs. Giuliano and Morton reported on their early experience with SLN mapping in patients with breast cancer. Giuliano and Morton showed that SLN mapping of the axillary LNs actually improved the ability to detect axillary LN metastasis when compared to standard axillary LN dissection (ALND). After further refinement of the procedure, Giuliano reported, in 1997, that SLN mapping, in experienced hands, could identify the SLN in 94% of breast cancer patients (all of these early study patients also underwent simultaneous ALND for comparison). In Giuliano's hands, the tumor status of the axillary SLN was confirmed to be highly accurate in staging the entire axilla of patients. In all cases where the SLN was negative for tumor, no tumor could be found in the remaining axillary LNs. While this 0% false-negative rate (i.e., having a negative SLN in the presence of positive non-SLNs) remains exceptional among reported studies to date, typical false-negative rates of 2 to 4% have been reported by other major breast cancer centers.

Although different techniques are being evaluated among various research centers, the SLN mapping procedure is relatively straightforward. Most centers use a radioactive tracer material, which is injected either into the area around the breast tumor or into the skin of the breast. This radioactive material decays very rapidly into non-radioactive substances, and subjects the patients to approximately the same radiation exposure as a routine chest x-ray. A special nuclear medicine camera is then used to follow the tracer material as it tracks within the lymphatic vessels on its way to the SLN(s). In most cases, 1 or 2 axillary SLNs are identified. Occasionally, SLNs adjacent to the sternum (breast bone) are also found. The patient is then taken to the operating room, and using a portable Geiger counter-like device to detect the radioactive tracer material, the surgeon can then hone in on the area of the SLNs. Many surgeons also use a special blue dye, which is also injected near the tumor or in the skin. The combination of increased radioactive "counts" in a LN (i.e., a "hot" LN) and blue discoloration (from the blue dye) confirm the presence of a SLN. If the blue dye is not used by the surgeon, then the "hot" LN is the SLN. All SLNs are removed through a very small incision in the armpit, and the pathologist then carefully examines them.

In addition to reducing the risk of complications when compared to ALND, the application of the SLN mapping concept to patients with breast cancer increases the pathologist's ability to detect even tiny deposits of tumor in the SLN. Patients with tumor-positive SLNs are usually offered complete ALND unless they wish to participate in one of several research trials that are looking at the prognostic impact of axillary LN disease. Outside of one of these approved multi-institutional research trials, patients with positive SLNs are recommended to undergo complete ALND at this time.

It should be noted that SLN mapping in breast cancer patients is not yet "standard-of-care," and more research needs to be done regarding the implications of both micro- and macro-metastatic disease in the SLN. Moreover, the procedure requires a bit of practice to master. Surgeons are generally advised that they should complete at least 30 SLN mapping cases under the supervision of an experienced surgeon. During these first 30 cases, ALND is also performed to allow the surgeon-in-training to compare his or her false-negative rates as the procedure is learned. Simply attending a weekend course, watching another surgeon "do it," or reading up on the subject are not sufficient. Moreover, surgeons offering patients "observation only" following the removal of tumor-positive SLNs should probably be avoided at this time outside of a research trial. The omission of complete ALND in such patients needs to be constrained to well-designed and monitored research protocols in order for all of us to learn about the potential implications of such a decision.

In summary, SLN mapping has revolutionized the care of patients with melanoma, and more recently, breast cancer patients as well. While more data needs to be collected in order to understand all of the implications of SLN mapping (with or without ALND), this is an exciting development for patients with breast cancer, as most such patients will be found not to have positive axillary SLNs following SLN mapping.

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Supportive Cancer Care: by Ernest H. Rosenbaum, MD & Isadora R. Rosenbaum, MA
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