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Originally published as Ann Surg Oncol Early Release 10.1245/ASO.2003.10.905 on November 10, 2003

Annals of Surgical Oncology 10:1131-1132 (2003)
© 2003 Society of Surgical Oncology
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EDITORIALS

Sentinel Lymph Node Biopsy for Breast Cancer: Does Anybody Not Need One?

Hiram S. Cody, III, MD

From the Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York.

Correspondence: Address correspondence to: Hiram S. Cody III, MD, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021; Fax: 212-794-5812 ; E-mail: codyh{at}mskcc.org

Ten years after the pioneering reports of Krag1 and Giuliano,2 sentinel lymph node (SLN) biopsy has become a new standard of care for axillary node staging in breast cancer. A substantial literature documents that SLN biopsy (1) is feasible and accurate, (2) works well in a wide range of practice settings, (3) is sufficiently robust to withstand variations in technique, (4) increases staging accuracy by allowing enhanced pathologic analysis, (5) has less morbidity than axillary lymph node dissection (ALND), and (6) gives local control comparable to that of ALND. These findings, entirely the result of observational studies, are now supported by the first level I evidence, a landmark prospective, randomized comparison of SLN biopsy and ALND, by Veronesi et al.3

Despite the progress mentioned above, case selection remains a subject of debate. In the developmental phase of SLN biopsy, all procedures were validated by a "backup" ALND and patients were selected based both on a low anticipated risk of axillary metastasis and the absence of other putative "contraindications." Most authors unanimously exclude patients with the "major contraindications" listed below, and variably exclude patients for other reasons as well (Table 1).


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  		TABLE 1. "Contraindications" to SLN biopsy
 
This level of caution, entirely appropriate for a new and unproved operation, is no longer necessary, and few (if any) contraindications remain. The success of SLN biopsy is independent of the method of breast biopsy,4 the timing of biopsy,5 tumor size,6–8 multicentricity,9 palpability,10 and volume of tissue excised.5 SLN biopsy is reasonable for prophylactic mastectomy11 (a setting where unsuspected invasive cancer will be found in approximately 5% of cases) and for extensive ductal carcinoma in situ [DCIS] requiring mastectomy12 (a setting where 10% to 15% of patients will be found to have invasive cancer in the surgical specimen13). Prior axillary surgery is not a contraindication; SLN biopsy appears to work well in the reoperative setting14 (especially in patients with fewer than 10 nodes removed at the earlier operation), and following previous radiotherapy. These findings are particularly relevant for patients with recurrence in the conserved breast, whose cancer was previously staged by SLN biopsy. SLN biopsy appears to be accurate following neoadjuvant therapy,15 although it may be less accurate for inflammatory (vs. noninflammatory) cancers.16 SLN biopsy would seem to be safe even in pregnancy; radiation exposure from the typical radiotracer dose of 99mTc (0.1 to 1 mCi, 3.7 to 37 MBq) is small,17 as is the risk of a hypotensive allergic reaction to blue dye (0.5%).18 Finally, SLN may prove useful even in patients with a clinically positive axilla. Previous studies19 from the era of ALND show that clinical examination finding of the axilla is falsely negative or falsely positive in approximately 25% of cases, and we have recently made the same observation (personal communication, M. Specht); among SLN biopsy patients with unequivocally positive clinical examination by two experienced surgeons, 22% proved node-negative. The risk of a false-negative clinical axillary examination is well recognized, but the risk of a false-positive examination is not, and SLN biopsy deserves a larger role in this context.

In this issue of the Annals of Surgical Oncology, Intra et al.20 address one more aspect of case selection for SLN biopsy, that of DCIS with microinvasion. They found a positive SLN in 9.7% (4/41) of patients with microinvasive DCIS, results similar to our own. Three of four had disease limited to the SLN, but two of four had macrometastases (>=2 mm), and one of these had four additional positive nodes on completion ALND. The authors conclude that SLN biopsy is indicated for microinvasive DCIS, "a true invasive breast carcinoma with metastatic potential," and we agree entirely.

Of interest, in a companion study,21 they reported the results of SLN biopsy for pure DCIS and reach a different conclusion. By excluding even those patients found in retrospect to have microinvasion (i.e., information not available before definitive surgery), they found a positive SLN in 3.1% (7/223); six of seven had disease limited to the SLN, and none had positive nodes on completion ALND. They conclude that SLN biopsy is not indicated for pure DCIS, except for lesions at increased risk of occult invasion (i.e., those that are extensive or require mastectomy). Again, we would agree (and currently perform SLN biopsy in approximately 25% of our DCIS patients) but would add a significant caveat.

Is SLN biopsy really indicated for a 10%, but not for a 3%, probability of a positive result? If so, where should we draw the line? Many patients will accept substantial surgical22 or chemotherapy-related23 morbidity for a survival advantage as small as 1% (or even for prognostic information that will not alter therapy), and we would argue that the decision to perform SLN biopsy in DCIS must be shared with the patient. The prognostic significance of a positive SLN in DCIS, of course, is unknown and will require long-term follow-up to resolve; this information too must be shared with the patient. All of us, physicians and patients alike, manage uncertainty differently and in the ways that work best for us.

In summary, breast cancer is a heterogeneous disease and SLN biopsy increasingly appears to encompass this heterogeneity. It is a reasonable option for most breast cancer patients with nonmetastatic disease. For a subset of patients at both ends of the spectrum, those with low risk DCIS and those with inflammatory cancer, the jury is still out.

Received for publication October 1, 2003. Accepted for publication October 16, 2003.

REFERENCES

  1. Krag DN, Weaver DL, Alex JC, et al. Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol 1993; 2: 335–40.[CrossRef][Medline]
  2. Giuliano AE, Kirgan DM, Guenther JM, et al. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 1994; 220: 391–401.[Medline]
  3. Veronesi U, Paganelli G, Viale G, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 2003; 349: 546–53.[Abstract/Free Full Text]
  4. Wong SL, Edwards MJ, Chao C, et al. The effect of prior breast biopsy method and concurrent definitive breast procedure on success and accuracy of sentinel lymph node biopsy. Ann Surg Oncol 2002; 9: 272–7.[Abstract/Free Full Text]
  5. Haigh PI, Hansen NM, Qi K, et al. Biopsy method and excision volume do not affect success rate of subsequent sentinel lymph node dissection in breast cancer. Ann Surg Oncol 2000; 7: 21–7.[Abstract]
  6. Chung MH, Ye W, Giuliano AE. Role for sentinel lymph node dissection in the management of large (> or = 5 cm) invasive breast cancer. Ann Surg Oncol 2001; 8: 688–92.[Abstract/Free Full Text]
  7. Bedrosian I, Reynolds C, Mick R, et al. Accuracy of sentinel lymph node biopsy in patients with large primary breast tumors. Cancer 2000; 88: 2540–5.[CrossRef][Medline]
  8. Olson JA, Jr, Fey J, Winawer J, et al. Sentinel lymphadenectomy accurately predicts nodal status in T2 breast cancer. J Am Coll Surg 2000; 191: 593–9.[CrossRef][Medline]
  9. Tousimis E, Van Zee KJ, Fey JV, et al. The accuracy of sentinel lymph node biopsy in multicentric and multifocal breast cancers. J Am Coll Surg 2003; 197: 529–35.[CrossRef][Medline]
  10. Liberman L, Cody HS, III. Percutaneous biopsy and sentinel lymphadenectomy: minimally invasive diagnosis and treatment of nonpalpable breast cancer. AJR Am J Roentgenol 2001; 177: 887–91.[Abstract/Free Full Text]
  11. Dupont EL, Kuhn MA, McCann C, et al. The role of sentinel lymph node biopsy in women undergoing prophylactic mastectomy. Am J Surg 2000; 180: 274–7.[CrossRef][Medline]
  12. Klauber-DeMore N, Tan LK, Liberman L, et al. Sentinel lymph node biopsy: is it indicated in patients with high-risk ductal carcinoma-in-situ and ductal carcinoma-in-situ with microinvasion? Ann Surg Oncol 2000; 7: 636–42.[Abstract]
  13. 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: 513–9.[Medline]
  14. Port ER, Fey J, Gemignani ML, et al. Reoperative sentinel lymph node biopsy: a new option for patients with primary or locally recurrent breast carcinoma. J Am Coll Surg 2002; 195: 167–72.[CrossRef][Medline]
  15. Breslin TM, Cohen L, Sahin A, et al. Sentinel lymph node biopsy is accurate after neoadjuvant chemotherapy for breast cancer. J Clin Oncol 2000; 18: 3480–6.[Abstract/Free Full Text]
  16. Stearns V, Ewing CA, Slack R, et al. Sentinel lymphadenectomy after neoadjuvant chemotherapy for breast cancer may reliably represent the axilla except for inflammatory breast cancer. Ann Surg Oncol 2002; 9: 235–42.[Abstract/Free Full Text]
  17. Waddington WA, Keshtgar MR, Taylor I, et al. Radiation safety of the sentinel lymph node technique in breast cancer. Eur J Nucl Med 2000; 27: 377–91.[CrossRef][Medline]
  18. Montgomery LL, Thorne AC, Van Zee KJ, et al. Isosulfan blue dye reactions during sentinel lymph node mapping for breast cancer. Anesth Analg 2002; 95: 385–8.[Abstract/Free Full Text]
  19. Fisher B, Wolmark N, Banes M. The accuracy of clinical nodal staging and of limited axillary dissection as a determinant of histologic nodal status in carcinoma of the breast. Gynecol Obstet 1981; 152: 765–72.
  20. Intra M, Zurrida S, Maffini F, et al. Sentinel lymph node metastasis in microinvasive breast cancer. Ann Surg Oncol 2003: 10; 1160–5.[Abstract/Free Full Text]
  21. Intra M, Veronesi P, Mazzarol G, et al. Axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast. Arch Surg 2003; 138: 309–13.[Abstract/Free Full Text]
  22. Galper SR, Lee SJ, Tao ML, et al. Patient preferences for axillary dissection in the management of early-stage breast cancer. J Natl Cancer Inst 2000; 92: 1681–7.[Abstract/Free Full Text]
  23. Simes RJ, Coates AS. Patient preferences for adjuvant chemotherapy of early breast cancer: how much benefit is needed? J Natl Cancer Inst Monogr 2001; 146–52.



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