Lymphatic Mapping in the Treatment of Breast Cancer

Dr. Cox and his colleagues should be commended for sharing their appreciable experience in treating breast cancer patients with lymphatic mapping and sentinel lymphadenectomy, and for their contributions to the literature and the training of surgeons. They have added considerably to the evolution of a technique that can accurately stage patients with minimal morbidity.

The authors perform sentinel lymphadenectomy by using a preoperative technetium-labeled sulfur(Drug information on sulfur) colloid injection combined with intraoperative injection of blue dye. In this prospective study, the sentinel node could be identified in 94.4% of cases. This high success rate is similar to the 93.5% rate reported in our most recent series using blue dye alone,[1] and is also similar to the experience of others with radiocolloid alone.[2]

Cox et al reported a false-negative rate of 1/466 (0.21%), but not all of the study participants underwent complete axillary lymph node dissection if the sentinel node was negative and, therefore, the true false-negative rate is unknown. The authors attempted to compare identification rates of blue dye to radiocolloid, and found that blue dye detected sentinel lymph nodes in 59.8% of cases and radiocolloid in 67.8%.

In the first portion of this previously reported study, hot nodes were identified in 12 patients without any blue nodes being identified, and these were all free of metastases by hematoxylin and eosin staining.[2] It would be interesting to know whether any metastases could be detected in hot nodes that were not blue by the addition of immunohistochemistry performed on sections of the sentinel node. It is difficult to compare detection rates when neither technique was performed alone, however.

Why the Low Identification Rates?

A few technical points may be responsible for what we consider to be the authors’ low identification rate with blue dye, as well as with radiocolloid--both of which are lower than identification rates cited in other reports. First, it may be possible that preoperative injection of sulfur colloid, along with its 6 mL of saline, in patients operated on 1 hour later affects lymphatic uptake of blue dye.

Second, the elapsed time between isosulfan blue injection and the start of sentinel lymphadenectomy is not mentioned. Timing is critical for the successful use of blue dye. We inject isosulfan blue after the skin is prepared and the patient draped. We then compress the breast. The sentinel node dissection is started 5 minutes after injection if the primary lesion is in either outer quadrant or in the upper-inner quadrant. For lesions close to the axilla or lower-inner quadrant, dissection begins at 3 and 7 minutes after injection, respectively.

Finally, in our technique, sentinel lymph node dissection is always performed before lumpectomy. In the authors’ study, it is not stated clearly how many sentinel lymphadenectomies were performed after lumpectomy, which was "usually" done to remove residual radioactivity at the primary site to prevent false probe readings. This alone may have significantly altered blue dye transit to the axilla and interfered with blue node identification.

Using the blue dye technique that we have described,[3] the same results can be achieved without the added costs and issues related to radiation that arise with the use of radiocolloid. However, for surgeons who are just starting to try sentinel lymphadenectomy, the use of both radiocolloid and dye should increase the likelihood of finding a sentinel node.

The data presented for the detection of metastases are consistent with previous reports. If the 87 patients with ductal carcinoma in situ (DCIS) are excluded, the number of patients with positive sentinel nodes is 30.5%. It is not surprising that sentinel node positivity correlates with increasing tumor size, as has been found by others.

The use of specialized cytokeratin stains and precise pathologic interpretation that Cox and his group implemented after their initial study should lead to more accurate staging. These immunohistochemical techniques should be validated in their study by comparing the presence or absence of immunohistochemistry-detected micrometastases in the nonsentinel nodes to the sentinel node, analogous to the testing of the surgical procedure itself.[4]

Patients With Ductal Carcinoma in Situ

Patients with DCIS represent an interesting subgroup documented in this study. With immunohistochemistry, 4 (4.6%) of 87 DCIS patients were found to harbor metastases in the sentinel node; this is higher than the generally accepted historical rate of lymph node metastases of approximately 1%.

We agree with the authors’ recommendation that selected patients with DCIS, especially those with large tumors, high nuclear grade, and necrosis, should be entered into experimental sentinel lymphadenectomy protocols. We can only speculate that, in patients with DCIS, scrutiny of the sentinel node may be a simpler task for the pathologist than searching for a focus of microinvasion in extensive DCIS. If metastases are detected, microinvasion can be assumed.

Summary

In summary, this study confirms that lymphatic mapping and sentinel lymphadenectomy offer a practical alternative to complete axillary lymph node dissection. Although the technique of combined radiocolloid with intraoperative blue dye used by the authors is accurate, surgeons should use a technique with which they are comfortable and which they have confirmed at their own institution by performing sentinel lymphadenectomy followed by complete axillary lymph node dissection.

The authors have formulated guidelines for expanding the use of lymphatic mapping and sentinel lymphadenectomy to a wider scope of practicing surgeons. We concur strongly with Dr. Cox and his colleagues that surgeons using the technique at their own institution should validate each component of this multidisciplinary treatment procedure to ensure its accuracy. Only when that has been acomplished should surgeons offer sentinel lymphadenectomy without axillary lymph node dissection to their breast cancer patients.