(Radiology. 1999;213:526-529.)
© RSNA, 1999
Sentinel Lymph Node Mapping for Breast Cancer: Analysis in a Diverse Patient Group1
Janet F. Eary, MD,
David A. Mankoff, MD, PhD,
Lisa K. Dunnwald, CNMT,
David R. Byrd, MD,
Benjamin O. Anderson, MD,
Raymond S. Yeung, MD and
Roger E. Moe, MD
1 From the Division of Nuclear Medicine (J.F.E., D.A.M., L.K.D.) and the Department of Surgery (D.R.B., B.O.A., R.S.Y., R.E.M.), University of Washington Medical Center, Box 356113, Seattle, WA 98195-6113. Received September 10, 1998; revision requested October 26; final revision received February 24, 1999; accepted April 6. Supported in part by grant CA72064 from the National Institutes of Health. Address reprint requests to J.F.E.
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Abstract
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PURPOSE: To evaluate sentinel lymph node mapping in patients with breast cancer.
MATERIALS AND METHODS: Sixty-two patients with breast cancer scheduled to undergo axillary nodal dissection underwent scintigraphic localization of sentinel lymph nodes with filtered technetium 99m sulfur colloid. At surgery, isosulfan blue was injected. Sentinel nodes were identifiable by blue color and by radioactivity with hand-held gamma probe. Results were analyzed statistically.
RESULTS: A sentinel lymph node was identified in 49 patients (79%). Lymph nodes were positive for metastatic disease in 26 patients (42%). The mapping success rate was 78% (n = 21) in the 27 patients with no prior surgery, 78% (n = 18) in the 23 patients with prior surgery, and 86% (n = 12) in the 14 patients with prior chemotherapy. Axillary nodes were positive in 11 (41%) of the 27 patients with no prior intervention, six (26%) of the 23 patients with prior surgery, and 10 (71%) of the 14 patients with prior chemotherapy. There were no false-negative findings in patients without prior intervention. Four patients with positive nodes had false-negative sentinel nodes.
CONCLUSION: Sentinel lymph node mapping and biopsy without axillary dissection is appropriate in patients with breast cancer who have not undergone prior intervention. Further study is necessary to ascertain the accuracy of the procedure for patients who have undergone presurgical chemotherapy or previous excisional biopsy.
Index terms: Breast neoplasms, 00.32 • Lymphatic system, neoplasms, 997.33 • Lymphatic system, radionuclide studies, 00.12961
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Introduction
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Sentinel lymph node mapping and biopsy is an established technique to assess the metastatic spread of melanoma in regional lymph nodes (1–3). This technique has been extended to breast cancer for evaluation of the axilla in disease staging (4–7). Breast cancer treatment planning relies on determining the presence of metastatic disease and the number of positive lymph nodes in the ipsilateral axilla. This is a topic that has generated much interest, as axillary dissection for lymph node staging in patients with breast cancer carries with it substantial levels of morbidity.
Preparing to offer this technique to patients with breast cancer in our clinical practice, we sought a conservative approach in our diverse patient population. This group includes patients with locally advanced disease, as well as patients with early breast cancer who previously have undergone an intervention such as excisional biopsy. Our analysis was carried out to determine which patient subgroup would be most appropriate for staging the axilla and avoiding axillary dissection. This analysis was also performed to determine the ability to accurately predict the disease status of the axillary lymph nodes with sentinel lymph node evaluation in the diverse population of patients with breast cancer.
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MATERIALS AND METHODS
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Patients
Patients who were scheduled to undergo axillary nodal dissection were referred from the University of Washington Breast Cancer Specialty Center, Seattle. Sixty-two patients with a mean age of 56.1 years (age range, 26–88 years) were examined. Fifty had tumors that were palpable masses or palpable cavities from recent excisional biopsy, and 12 had nonpalpable abnormalities that required mammographic or ultrasonographic localization for surgery. Twenty-seven of these patients had not undergone biopsy or had undergone only needle biopsy prior to the procedure. They included patients with T1 and T2 tumors. Twenty-three patients had previously undergone excisional biopsy, and 14 patients had undergone neoadjuvant chemotherapy for locally advanced breast cancer (typically T3 lesions or advanced axillary disease). Two patients had undergone both excisional biopsy and chemotherapy.
Patients signed informed consent documents approved by the University of Washington Human Subjects and Radiation Safety Committees.
Nuclear Medicine Mapping Procedures
Patients received injections of 1.0-mCi (37-MBq) technetium 99m sulfur colloid after passage through a 0.2-µm filter. The volume was adjusted to a total volume of 6 mL, which included 2 mL of sodium bicarbonate to adjust the pH to be neutral. Patients with palpable masses received four 1.5-mL midplane injections around the palpable mass. Injections in patients who had undergone excisional biopsy were in the four quadrants at the midplane of the resection cavity immediately outside the indicated area (determined with palpation). Patients with nonpalpable masses received a single 6-mL injection through a localizing wire introducer needle. Sterile tubing was attached to the needle hub in a sterile fashion over the free end of the localizing wire and was retained for use in surgery. Injection was followed by gentle massage of the injected area for approximately 3 minutes (Fig 1).
Immediately after injection, patients were put in the supine position, with the shoulder of the injected side propped up posteriorly at a 45° angle. The elbow was placed up, which allowed acquisition of a scintigraphic image of the axilla and lateral aspect of the breast (axillary plane view) at a straight lateral or steep oblique angle. In the instances where the breast injection site was visible in the imaging field, the injection site was shielded with a square 2 x 2-inch (5.1 x 5.1-cm) piece of lead foil.
Localized lymph nodes were then marked on the patient's skin with a radioactive marker by using the gamma camera (model 300AC; GE Medical Systems, Milwaukee, Wis). Scintigraphy was performed at 45° to ascertain the depth of the lymph node. The shift in the apparent location of the sentinel lymph node viewed at 45° from the axillary plane image indicated the nodal depth. A mark was placed on the skin to note this distance. By using simple geometry, the distance between the sentinel node mark on the skin in the axillary plane view and the node (skin) location at a 45° angle view approximately represented the depth to the visualized node from the skin surface. The lymph node location in the correct surgical anatomic position was confirmed by using a hand-held gamma probe (model 1500 Portable or Neo200; Neoprobe, Dublin, Ohio). Finally, an anterior chest scintigraphic view was acquired to note the presence of internal mammary nodes (Figs 2, 3).
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Figure 2. Left: Anterior axillary scintigraphic image. Right: Lateral axillary scintigraphic image. Images show a sentinel lymph node (arrows) for a left breast cancer. The injection site is visible as the large, irregular, medial area of uptake. The tail of activity that extends from the injection site is additional activity associated with this site.
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Figure 3. Left: Anterior axillary scintigraphic image. Right: Oblique axillary scintigraphic image. Images show a sentinel lymph node for a left breast cancer and the presence of an internal mammary sentinel node (arrowheads). The small focus of activity just below the marked nodal focus is activity in the injection site that shows up even with use of a lead shield (used to decrease injection site activity in the image for better contrast of labeled nodal foci).
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Surgery Methods
Approximately 5 mL of isosulfan blue 1% (Lymphazurin Dye; U.S. Surgical, Norwalk, Conn) was injected in the same locations as was the 99mTc sulfur colloid by the surgeons in the operating room. After an incision in the axilla, the sentinel node was localized, again by using the hand-held gamma probe and by visualizing blue dye in the lymph node. Sentinel node confirmation was by the presence of the blue color and/or by counts in the excised node of at least three times the surgical bed background. The sentinel node was removed and tagged separately for histopathologic analysis, which was followed by a level 1 or level 2 axillary dissection in all patients.
Data Analysis
We grouped patients according to whether the sentinel lymph nodes were identified with radiation detection, blue dye visualization, or both by consensus (L.K.D., D.A.M.) and the results of lymph node histopathologic analyses. In addition, patients and their results were grouped by using the categories of no prior intervention, prior surgery, and prior chemotherapy.
The significance of the difference in the rates of success in imaging the sentinel node was determined with the 
2 test (8). Differences with a P value of less than .05 were considered statistically significant. The number of positive lymph nodes and the false-negative metastasis rate were analyzed for each patient group.
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RESULTS
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The mean number of nodes removed during axillary dissection per patient was 18 (range, four to 40 nodes). Overall, 42% of patients had positive nodes, with a mean of 3.7 positive nodes per patient. In the patients with no prior intervention, 41% had lymph nodes positive for the presence of metastases; in patients with prior surgery, 26% had positive lymph nodes; and in patients with prior chemotherapy (with T3 tumors), 71% had positive lymph nodes (Tables 1, 2).
The overall success rate in lymph node mapping for sentinel lymph node identification at surgery was 79% (49 of 62 patients)(Table 3). Sentinel lymph nodes were identified as being both blue and radioactive at surgery in 55% of patients with successful cases, as only blue in 8%, and as only radioactive in 37%. The success rate, by category, was 78% in the group without prior intervention, 78% in the group with prior surgery, and 86% in the group with prior chemotherapy (with T3 tumors) (not a significant difference). The mean time to lymph node visualization after injection and patient positioning was 27 minutes (range, 2–120 minutes). The mean number of sentinel lymph nodes visualized at imaging was 1.5 (range, one to four sentinel lymph nodes).
Twenty-two patients with sentinel nodes identified had lymph nodes positive for metastases at axillary dissection. The sentinel node was positive in 18 of these 22 patients. The false-negative rate for predicting metastases by analyzing the sentinel node at axillary dissection was 0% (n = 0) in the 21 patients with no prior intervention who had successful lymphatic mapping, 6% (n = 1) in the 18 patients with prior surgery and successful lymphatic mapping, and 25% (n = 3) in the 12 patients with prior chemotherapy and successful lymphatic mapping. In the 27 patients in whom the sentinel node was identified as both radioactive and blue, 7% (n = 2) had false-negative results; in the 18 patients in whom the node was identified only because of radioactivity, 11% (n = 2) had false-negative results; and in the four patients in whom the node was identified only because of blue color, 0% (n = 0) had false-negative results (Table 4).
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DISCUSSION
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These study findings showed a high success rate in identifying the sentinel lymph node in the axillae of patients with breast cancer. This held true even in many patients with prior intervention. These rates of successful identification of the sentinel lymph nodes are similar to those previously published for larger series (4,6,9). However, at our tertiary care hospital the addition of patients with locally advanced disease (the chemotherapy group) at presentation was to our knowledge unknown for axillary staging by using this procedure. Of interest is the high false-negative rate in patients in this group. These patients, with known large-volume disease and probable lymph node metastases, received presurgical chemotherapy in accordance with current treatment practices (10–12). Therefore, they presented a diagnostic challenge, with tumor shrinkage and attendant changes in tissue characteristics as a result of chemotherapy. It is not surprising that false-negative results were observed in these patients.
These data also confirm results from previous studies (4,5,9) that show accurate staging in patients without prior intervention. Our overall false-negative rate was only 8%; however, the small number of patients in our study warrants further investigation in the subset of patients with prior surgery. We demonstrated the ability to distinguish sentinel lymph nodes in patients with no intervention. The similarity of the false-negative rate and imaging results with those of previously reported series allowed us to conclude that patients with no prior intervention could be subjected to the sentinel node biopsy procedure safely.
The results of this study have had an effect on clinical practice at our institution. We now offer sentinel node mapping and biopsy without axillary dissection for patients with T1 (<2.0-cm) tumors who have not undergone prior intervention. Further, sentinel mapping is avoided in patients who have received prior chemotherapy. We will continue to study specific groups of patients under our study protocol who have had prior surgery and those with T2 or larger lesions.
The results of this study confirm our conviction that a conservative approach to introducing this technique to the various subgroups of patients with breast cancer at presentation warrants careful study. It is our belief that a premature shift in standard practice to only sentinel node biopsy by surgeons just beginning this technique may result in missed positive axillary nodes. This could lead to undertreatment or to a delayed axillary tumor recurrence. In our wish to avoid this serious possibility, this conservative approach of using this new procedure in our patient population enabled us to proceed with confidence in offering sentinel lymph node mapping and biopsy as an alternative to axillary dissection for staging early breast cancer.
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Acknowledgments
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We acknowledge the assistance of Finbarr O'Sullivan, PhD, in data analysis.
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Footnotes
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Author contributions: Guarantor of integrity of entire study, J.F.E.; study concepts, J.F.E., D.A.M., D.R.B., B.O.A., R.S.Y., R.E.M.; study design, J.F.E., D.A.M., D.R.B.; definition of intellectual content, J.F.E.; literature research, J.F.E., D.A.M., D.R.B.; clinical studies, J.F.E., D.A.M., D.R.B., R.E.M., B.O.A., R.S.Y.; data acquisition and analysis, L.K.D.; statistical analysis, L.K.D.; manuscript preparation, J.F.E.; manuscript editing and review, all authors.
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Abstract
Introduction
