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10.1245/ASO.2004.12.913
Annals of Surgical Oncology 11:222S-226 (2004)
© 2004 Society of Surgical Oncology
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SUPPLEMENT

Novel Techniques in Sentinel Lymph Node Mapping and Localization of Nonpalpable Breast Lesions: The Moffitt Experience

Charles E. Cox, MD, Ben Furman, MD, Elisabeth L. Dupont, MD, James W. Jakub, MD, Nicholas Stowell, BS, John Clark, BS and Mark Ebert, BS

From the Department of Surgery, Comprehensive Breast Cancer Program, H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa, Florida.

Correspondence: Address correspondence and reprint requests to: Charles E. Cox, MD, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612; Fax: 813-979-7287; E-mail: coxce{at}moffitt.usf.edu

ABSTRACT

The concept of lymphatic mapping has helped to redefine the clinical significance of lymph nodes with respect to breast cancer. The combination technique using both blue dye and radiocolloid is the most effective method of lymphatic mapping. The data in the literature support the concept that all patients undergoing lumpectomy or especially mastectomy should undergo lymphatic mapping if a diagnosis of invasive cancer is remotely possible. The low morbidity, high sensitivity, and specificity of mapping indicate its use for increasing numbers of patients thought initially not to be candidates for the procedure.

Key Words: Combination technique • Ductal carcinoma in situ • Lymphatic mapping • Radioactive seeds

Minimally invasive breast surgery combined with lymphatic mapping helps decrease morbidity and increase the comfort of patients with a diagnosis of breast cancer. Lymphatic mapping of sentinel lymph nodes in breast cancer is quickly becoming the standard of care at many institutions and is clearly changing the long-held paradigm of complete axillary lymph node dissection (CALND). There are a variety of techniques worldwide that employ various agents for lymphatic mapping. The use of isosulfan blue dye provides the surgeon with visual identification of sentinel nodes, while use of radiocolloid allows for radio-guided identification of sentinel nodes with use of a gamma probe.

The combination technique that employs both Tc99m-labeled sulfur colloid and isosulfan blue dye has been shown to be an effective method for lymphatic mapping.1 Our group was the first to report the combination technique using these two agents.2 This combination technique3,4 requires training for which we have demonstrated a learning curve. However, mastery of the combination technique has been demonstrated by our work and that of others to improve sentinel node detection and reduce false-negative assessments in comparison with single-agent techniques used in lymphatic mapping.5

SENTINEL NODE MAPPING IN PATIENTS WITH DCIS

Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous group of lesions with diverse clinical presentations, histological features, and malignant potentials. Before the mammographic era, the frequency of diagnosing DCIS was 1% to 5.6% of all breast cancers.6 However, major advances in high-quality mammography have dramatically increased the detection of DCIS. From 1983 to 1992, DCIS was the most rapidly growing subtype of breast cancer, with a growth rate of 500% in new breast cancer cases.7 DCIS now represents between 15% and 25% of all new breast cancer diagnoses. This represents between 28,000 and 46,000 new cases detected each year, of which only 2% (900) will lead to death.7

Management of this disease has progressed over the years. Modified radical mastectomy was used until the 1980s. Lumpectomy, with axillary lymph node removal and radiation therapy, was used until about 1994, when most had abandoned CALND. At present, lumpectomy plus or minus radiation is being offered to women on the basis of the size of the lesion removed, the newly proposed grading system for DCIS, and the margin of resection, as proposed by Silverstein and colleagues.7

The need for lymph node evaluation in the management of DCIS has been all but abandoned because of the low incidence of nodal disease (1% to 2%) and high morbidity of lymph node dissection. Our group switched from lymph node dissection to lymphatic mapping in 1994. We currently perform lymphatic mapping with the combination technique for patients with a diagnosis of DCIS, for several reasons. First, DCIS at diagnosis is frequently upstaged on final pathology to an invasive cancer, requiring mapping. Second, there are no predictive models in the literature to identify which DCIS patients will require mapping. Third, many patients require mastectomy as treatment for DCIS. If mastectomy is performed without mapping, those patients are consigned to CALND if they have invasive disease on final pathology. Mapping has little risk, negligible morbidity, and high accuracy and sensitivity when performed at the time of initial treatment.

REPLACING NEEDLE LOCALIZATION WITH RADIO-GUIDED TECHNIQUES

Because of increased mammographic screening and improved imaging techniques, there has been a rapid increase in the detection of nonpalpable breast lesions. This has resulted in a greater proportion of lumpectomies and operative breast biopsies requiring radiographic localization. The current standard technique for preoperative localization of these lesions is wire localization (WL): a thin, hooked wire is guided through the skin to the lesion; the surgeon uses the wire to help guide the excision. This technique has several problematic features. First, the ideal skin-entry site that enables the radiologist to accurately position the wire’s tip at the lesion is often distant from the ideal skin-incision site for the surgeon. This results in extensive dissection or perhaps compromise in the positioning of the incision. In addition, the surgeon must base the incision site and the direction of dissection on the mammograms, with the wire serving mainly to confirm correct judgment. Another reported disadvantage is that the thin wire can be transected,8 in which case all guidance to the lesion is lost and foreign bodies can be left within the breast. Finally, because the wire protrudes extradermally from the breast, displacement of the wire has occurred during confirmatory mammography or patient transfers9,10; in addition, the excision must take place on the same day as the localization to reduce the incidence of infection.

Several techniques have been described to deal with some of the shortcomings of WL. Some have used intraoperative ultrasound in select cases. In 2000, Gennari et al.11 reported a new method of radio-guided breast biopsy using Tc99m-labeled albumin (a technique known as radio-guided occult lesion localization, or ROLL). Our group at H. Lee Moffitt Cancer Center has initiated various studies involving the use of radioactive seed localization (RSL).12 A titanium seed containing 0.29 µCi of iodine-125 (I125), most commonly used for prostate brachytherapy, is employed to localize nonpalpable breast lesions. The I125 can be used in conjunction with the Tc99m employed with lymphatic mapping.

RESULTS

Since its implementation at the Moffitt Cancer Center, 3174 lymphatic mappings have been done with the combination technique. Of these, 3095 (97.5%) were successful and 79 (2.5%) were failures. Over time the failure rate of lymphatic mapping (not able to locate a sentinel node) has decreased considerably (Fig. 1).



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  		FIG. 1. Overall learning curve for combination technique of lymphatic mapping at the H. Lee Moffitt Cancer Center.

 
Our data show that the combination technique is reliable for the detection of sentinel lymph nodes (Table 1). In our breast cancer database, a total of 3002 sentinel lymph nodes have been recorded as both hot and blue (visually and radiologically determined), hot only, blue only, or neither hot nor blue. Of the 3002 sentinel nodes, 1881 (63%) were both blue and hot, 329 (11%) were blue only, and 610 (20%) were hot only (Table 1). The remaining 182 nodes (6%) were neither hot nor blue; these nodes were completely replaced by cancer but had blue lymphatic channels.


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  		TABLE 1. Comparison of sentinel lymph node (SLN) identification rates and node characteristics
 
Past studies show that there is a learning curve associated with the combination technique. A certain number of cases are required for surgeons to adequately perform successful lymphatic mapping. Our experience indicates that 22 cases must be performed for the failure rate to drop below 10%, and 54 cases for it to drop below 5% (Fig. 2). Over a period of time the failure to locate a sentinel node can drop to less than 2.5%, as seen at our facility. Most of the unsuccessful mapping procedures occurred at the beginning of the Moffitt experience; over time, unsuccessful mappings are infrequent and are related more to patient factors (body mass index and age) than surgical skill. In fact, the failure rate for the last 500 mappings at Moffitt is only 1.8%, and after the first 1000 cases the failure rate decreased to less than 2% for all surgeons.



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  		FIG. 2. Composite combination technique lymphatic mapping learning curve: mean values for six surgeons.

 
Between November 1994 and May 2002, 437 patients had an initial diagnosis of DCIS, and 62 other patients had an initial diagnosis of DCIS with microinvasion (DCIS [Tmic]). As shown in Table 2, 33 patients (7.6%) in the DCIS group and 14 (22.6%) in the DCIS (Tmic) group had their tumors upstaged to invasive cancers at the time of definitive surgery. About 8.2% of patients with DCIS or DCIS (Tmic) had positive sentinel lymph nodes (Table 2).


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  		TABLE 2. The Moffitt experience with upstaged DCIS and lymph node metastases associated with DCIS
 
Two studies involving RSL breast biopsies and lumpectomies have been completed at Moffitt. In both studies 100% of radioactive seeds were retrieved, and no seeds were dislodged in 231 patients that underwent RSL. The first study compared RSL to WL and found it to be similar in its effects, except that the rate of positive surgical margins after reexcision was 26% with RSL, vs. 57% with WL (P = .02).12 In the second study, RSL effectively eliminated the need for a post-biopsy radiograph of the specimen in 98 (79%) of 124 patients.13 The tumor was grossly identified by the pathologist within the extracted specimen in these 98 patients, thus eliminating the need for the post-biopsy radiograph. The 26 remaining patients all required specimen radiographs because the pathologist could not grossly observe the lesion within the specimen. Of the 26 patients who required specimen radiographs, 22 (85%) had microcalcifications as their abnormality.

DISCUSSION

Breast cancer surgery has become a much less invasive technique. Lymphatic mapping to identify sentinel lymph node(s) is more cost-effective for the patient and helps to decrease the morbidity associated with CALND. The use of radiocolloid and blue dye in lymphatic mapping not only allows the surgeon to visually recognize the sentinel nodes but also allows confirmation of SLNs by the use of the gamma probe. The technique is easier to learn and more accurate than the blue dye or radiocolloid technique alone. After a certain level of proficiency is gained from the first 50 cases (5% failure rate), the long-term failure rate is around 2%.

Because mapping failure is mainly a result of a patient’s age and weight, elderly patients that have a high body mass index are at a higher risk of mapping failure (Fig. 3). Surgeons should not abandon good clinical judgment while employing lymphatic mapping; they should remain conscious of palpable abnormal lymph nodes that are neither hot nor blue, because of lymph node replacement by tumor, yet are still clearly sentinel nodes.



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  		FIG. 3. Nomogram relating lymphatic mapping success to age and body mass index (BMI).

 
The current standard of care for patients with a definitive diagnosis of DCIS does not include examination of regional lymph nodes for metastatic disease. However, patients with a biopsy diagnosis of DCIS prior to definitive treatment should undergo lymphatic mapping, so that the opportunity is not lost when the final diagnosis reveals invasive cancer. In our experience, 47 of 499 patients (9.4%) with a diagnosis of DCIS or DCIS (Tmic) had tumors that were eventually upstaged (Table 2). Those undergoing mastectomy would have required CALND if sentinel mapping had not been performed. The purpose of mapping these patients is not to find occult metastases in the lymph nodes but rather to eliminate the need for additional surgery due to upstaging to invasive cancer. Surgeons who do not employ lymphatic mapping for these patients will have to bring back roughly 10% of them to undergo less reliable mapping after lumpectomy or a CALND following mastectomy.14

Currently there is no method for determining which cases of DCIS are more likely to be upstaged to invasive ductal cancers. However, cases of DCIS (Tmic) are upstaged more frequently than normal DCIS cases. This lack of a definitive high-risk group calls for lymphatic mapping of all DCIS cases at the time of definitive lumpectomy or mastectomy.

Two prospective studies involving the use of a radioactive seed for localization of nonpalpable breast lesions have shown that RSL is an especially consistent technique. RSL is more effective than WL at decreasing the incidence of positive margins during lumpectomy or excisional biopsy. In addition, all WLs require post-sampling radiographs to show that the wire is intact and the lesion is within the specimen. RSL can grossly manifest to the pathologist that the lesion is within the specimen and can therefore decrease the need for post-sampling radiographs to only 21% (26 of 124 patients in the study13), compared with 100% for wire localizations. Elimination of the need for intraoperative radiographic analysis lowers costs and liberates more time in the operating room.

Another facet of RSL is that it can be used in conjunction with the Tc99m because of the separation of the radioactive peaks. This allows simultaneous mapping and RSL biopsy or lumpectomy. An added benefit is that the training for lymphatic mapping can be modified to include the RSL technique, and surgeons can learn both techniques in the same training session.

CONCLUSIONS

Lymphatic mapping with the combined dye/radiocolloid technique universally applied is the most effective means of sentinel node biopsy. All patients diagnosed with invasive cancer should undergo lymphatic mapping in conjunction with lumpectomy or mastectomy. Patients at risk for an occult invasive cancer, including patients with a diagnosis of DCIS or patients undergoing prophylactic procedures who are contemplating mastectomy, should be offered lymphatic mapping. Many patients whose tumors are upstaged to invasive cancers on final diagnosis following their definitive procedures would not be able to undergo postsurgical mapping or would require CALND. RSL of breast lesions is more effective than WL at decreasing the incidence of positive surgical margins and decreasing the need for post-biopsy specimen radiographs.

FOOTNOTES

Lymphatic mapping of sentinel lymph nodes in breast cancer is quickly becoming the standard of care at many institutions and is clearly changing the long-held paradigm of complete axillary dissection.

Received for publication November 16, 2003. Accepted for publication December 25, 2003.

REFERENCES

  1. Cox CE. Lymphatic mapping in breast cancer: combination technique. Ann Surg Oncol 2001; 8 (9 Suppl): 67S–70S.[Medline]
  2. Albertini JJ, Lyman GH, Cox C, et al. Lymphatic mapping and sentinel node biopsy in the patient with breast cancer. JAMA 1996; 276: 1818–22.[Abstract]
  3. Cox CE, Bass SS, Ku N, et al. Sentinel lymphadenectomy: a safe answer to less axillary surgery. Recent Results Can Res 1998; 152: 170–9.
  4. Cox CE, Haddad F, Bass SS, et al. Lymphatic mapping in the treatment of breast cancer. Oncology 1998; 12: 1283–98.[Medline]
  5. Cox CE, Salud CJ, Cantor A, et al. Learning curves for breast cancer sentinel lymph node mapping based on surgical volume analysis. J Am Coll Surg 2001; 193: 593–600.[CrossRef][Medline]
  6. Rosener D, Bedwani RN, Vana J, et al. Noninvasive breast carcinoma. Results of a national survey by the American College of Surgeons. Ann Surg 1980; 192: 139.[Medline]
  7. Silverstein J. Ductal carcinoma in-situ of the breast. Annual Review of Medicine: Selected Topics in the Clinical Sciences 2000; 51: 17–32.
  8. Homer MJ. Transection of the localization hooked wire during breast biopsy. AJR Am J Roentgenol 1983; 141: 929.[Medline]
  9. Davis PS, Wechsler RJ, Feig SA, et al. Migration of breast biopsy localization wire. AJR Am J Roentgenol 1988; 150: 787.[Free Full Text]
  10. Homer MJ, Pile-Spellman ER. Needle localization of occult breast lesions with a curved-end retractable wire: technique and pitfalls. Radiology 1986; 161: 547.[Abstract/Free Full Text]
  11. Gennari R, Galimberti V, De Cicco C, et al. Use of technetium-99m-labeled colloid albumin for preoperative and intraoperative localization of nonpalpable breast lesions. J Am Coll Surg 2000; 190: 692–8; 698–9.[CrossRef]
  12. Gray RJ, Salud C, Nguyen K, et al. Randomized prospective evaluation of a novel technique for biopsy or lumpectomy of nonpalpable breast lesions: radioactive seed versus wire localization. Ann Surg Oncol 2001; 8: 711–5.[Abstract/Free Full Text]
  13. Cox CE, Furman B, Stowell N, et al. Radioactive seed localization breast biopsy and lumpectomy: can specimen radiographs be eliminated? Ann Surg Oncol 2003; 10: 1039–47.[Abstract/Free Full Text]
  14. Cox CE, Nguyen K, Gray RJ, et al. Importance of lymphatic mapping in ductal carcinoma in situ (DCIS): why map DCIS? Am Surg 2001; 67: 513–21.[Medline]



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