Skip to main content

Advertisement

You are viewing the new BMC article page. Let us know what you think. Return to old version

Review | Open | Published:

Clinical aspects of sentinel node biopsy

Abstract

Sentinel lymph node (SLN) biopsy requires validation by a backup axillary dissection in a defined series of cases before becoming standard practice, to establish individual and institutional success rates and the frequency of false negative results. At least 90% success in finding the SLN with no more than 5-10% false negative results is a reasonable goal for surgeons and institutions learning the technique. A combination of isotope and dye to map the SLN is probably superior to either method used alone, yet a wide variety of technical variations in the procedure have produced a striking similarity of results. Most breast cancer patients are suitable for SLN biopsy, and the large majority reported to date has had clinical stage T1-2N0 invasive breast cancers. SLN biopsy will play a growing role in patients having prophylactic mastectomy, and in those with 'high-risk' duct carcinoma in situ, microinvasive cancers, T3 disease, and neoadjuvant chemotherapy. SLN biopsy for the first time makes enhanced pathologic analysis of lymph nodes logistically feasible, at once allowing greater staging accuracy and less morbidity than standard methods. Retrospective data suggest that micrometastases identified in this way are prognostically significant, and prospective clinical trials now accruing promise a definitive answer to this issue.

Introduction

Some of the best ideas in clinical medicine are simple ones, and SLN biopsy is one of these. The hypothesis that one or a few lymph nodes receive the first drainage from a tumor site, and that a regional node dissection and its morbidity might be avoided if the SLNs prove negative, is logical and intuitive. First suggested by Cabanas [1] in the context of penile cancer and conceived in its modern form in a 1992 report by Morton et al [2], SLN biopsy is rapidly emerging as a new standard of care in melanoma and breast cancer. The procedure has promise but remains investigational in patients with head and neck, urologic, gynecologic, and colorectal cancers. SLN biopsy's immediate potential is greatest among patients with breast cancer, by far the most significant group numerically, and will be the focus of this overview. Among an estimated 184,200 new cases of breast cancer in the United States last year [3], about 60% (110,000) had disease limited to the breast and might have avoided a conventional axillary lymph node dissection (ALND) through SLN biopsy.

By the end of 1999, 41 peer-reviewed pilot studies using radioisotope [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19] or blue dye [20,21,22,23,24,25,26,27,28,29,30] methods, or a combination of both [31,32,33,34,35,36,37,38,39,40,41,42] (Table 1), report the results of SLN biopsy validated by a 'backup' ALND in breast cancer patients. SLNs were identified in 90% of cases, correctly identified 93% of axillary node-positive individuals, and were the only site of nodal metastasis in 47% of these. An increasing number of centers, having completed validation studies of SLN biopsy, offer patients the option of no further axillary surgery if the SLN is negative. Despite this encouraging debut, SLN biopsy is a new operation, has a definite learning curve, and is highly multidisciplinary, requiring the cooperation of nuclear medicine physicians, surgeons, and pathologists. The techniques pertinent to each specialty continue to evolve, and many of these aspects remain the subject of debate. We have performed more than 3000 SLN biopsy procedures since 1996, and the following represents a distillation of our experience, recently reviewed in detail [43], and that of other workers.

Table 1 Cumulative results of sentinel lymph node (SLN) biopsy, 1993-1999

Protocol design and learning curve issues

The benefit of SLN biopsy seems clear, but the technique is a new one, the long term consequences are not fully defined, and the medicolegal risks are unknown. Institutions beginning to perform this procedure should do so under a formalized Institutional Review Board protocol, in which selection and technique are carefully specified, patients are fully informed, a backup axillary dissection is carried out to validate the early experience, and careful audits of individual and institutional results (short and long term) are maintained. A success of 90-95% in finding the SLN and no more than 5-10% false negative results would seem reasonable targets for validation trials.

We have found that success in localizing the SLN continued to improve over our first 500 cases, and that one-half of our false negative results occurred within the first six cases of each surgeon [44]. Cox et al [45] found that, to identify the SLN, surgeons required an average of 23 cases to achieve 90% success and 53 cases to achieve 95% success, although the SLN was falsely negative in only 2% of their node-positive patients [39]. While most authorities recommend that each surgeon initially perform 20-30 SLN procedures with a backup ALND, fewer validated cases may be necessary. McMasters et al [46], in a remarkable multi-institutional trial involving 806 patients and 99 surgeons, found that the frequency of successful mapping and of false negative results was identical whether the participating surgeons had prior experience of more than or fewer than 10 SLN operations.

SLN may be identified by either radioisotope or blue dye methods and, while each technique by itself enjoys the vocal support of a few investigators [10,21], an emerging international consensus (and our own experience [33,47,48]) supports the use of both methods in combination. We continue to find that about 10% of SLN, and 10% of positive SLN, are found by either dye or isotope alone, and presumably would have been missed by reliance on a single method. McMasters et al [46] demonstrate that false negatives occur half as often with a combined technique as with a single-agent SLN mapping technique.

Case selection

Most of the reported experience with SLN biopsy includes patients with clinical stage T1-2N0 invasive breast cancers. SLN biopsy has an emerging role in microinvasive cancers and in selected cases of duct carcinoma in situ, particularly those with a high risk of occult invasion (evidenced by a palpable mass or extensive disease requiring mastectomy). While neither group is normally considered for a conventional ALND, about 10% of microinvasive or high-risk duct carcinoma in situ patients harbor micrometastases in their SLN [49]. SLN biopsy is reasonable at the time of a prophylactic mastectomy, to avoid the need for reoperative ALND if invasive cancer is unexpectedly found in the breast (as is the case in perhaps 5% of prophylactic mastectomies). SLN biopsy works well for nonpalpable cancers requiring needle localization [50], and in the setting of a prior surgical biopsy [47]. While equally accurate for T1 and T2 cancers [51,52], high false negative rates occur in T3 cancers and in patients with surgical disruption of the axillary lymphatics by a large upper outer quadrant biopsy cavity. Diagnosis should, for this reason, be by fine-needle aspiration (FNA) or core needle biopsy whenever possible. Even in the setting of advanced disease, SLN biopsy may play a role in estimating response to neoadjuvant chemotherapy [53]. Finally, SLN biopsy is reasonable in selected patients with clinically palpable axillary nodes thought to be reactive, as long as the surgeon maintains a low threshold for default to conventional ALND.

Nuclear medicine aspects

Overall, radioisotope mapping of the SLN succeeds more often than blue dye (92% versus 81%; Table 1). Intuition would suggest that tracer injection into or directly adjacent to the tumor would most accurately identify the SLN. A number of studies, however, have found that SLN identified by intraparenchymal, 'subdermal', intradermal or subareolar injections [18,28,32,54,55] stage the axilla with comparable accuracy, and that the entire breast and its overlying skin function as a single lymphatic unit in most patients [56]. This may explain why such a wide variation in isotope techniques (dosage of isotope, carrier particle, route/timing/volume of injection, and definition of a successful result) produces such a similarity of outcome. We have achieved optimal success using blue dye injected intra-parenchymally and unfiltered [57] Tc-99m sulfur colloid in 0.05 cm3 saline injected intradermally [54] into a single site directly over the tumor, at a dose of 0.1 mCi for same-day and 0.5 mCi for day-before injection. In our most recent experience, we have identified the SLN in 97% of cases.

Preoperative lymphoscintigraphy is essential in the management of melanoma, and can indeed also show unexpected patterns of lymphatic drainage (supraclavicular, internal mammary, Rotter's node) in about 20% of breast cancer patients [58]. Because gross recurrence in these nonaxillary sites is a very rare event in early-stage breast cancer, the clinical relevance of this finding is uncertain, and the role of routine preoperative lymphoscintigraphy in breast cancer patients remains a matter of debate.

Surgical aspects

SLN biopsy is usually a straightforward and simple operation [43]. Before the procedure on the breast (excision or mastectomy), blue dye is injected into the breast just superolateral to the tumor (or biopsy) site, and isotope counts are taken from the axilla and the injection site in the breast using a hand-held gamma probe. An axillary incision is made, and the surgeon identifies and removes the SLN by looking for blue-stained lymphatic vessels or nodes and using the gamma probe to identify focally 'hot' nodes. All blue and/or hot nodes are removed until the axillary background counts fall below a threshold value; most authors report a median of two SLN per patient. Once the surgeon has passed the validation phase in which backup ALND is performed routinely, the SLN are submitted for frozen section and either tumor excision or mastectomy is performed while waiting for the pathologists's report. ALND is performed if the SLNs contain tumor or if there are clinically suspicious nonSLNs palpable at the time of surgery. Clinically suspicious nonSLNs were present in more than one-half of our false negative SLN biopsy procedures [43,47], suggesting that gross tumor involvement of the nodes may impair the uptake of both isotope and dye by the 'true' SLN. Careful intraoperative palpation of the axilla is an essential component of SLN biopsy, and the surgeon facing suspicious findings should not hesitate in defaulting to ALND.

Pathologic aspects

Frozen section analysis of the SLN, if positive, allows an immediate ALND, sparing the patient a reoperation. While limited in its ability to detect micrometastases (which predominate in the smallest invasive cancers), the frozen section of the SLN demonstrates sensitivity ranging from 40% for T1a to 60% for T2 cancers [59].

Lymph nodes in ALND specimens are normally examined by a single hematoxylin and eosin stained section. When nodes found to be negative by this standard method are further studied with serial sectioning and immunohistochemical stains for cytokeratins, missed metastases are found in 10-20% of cases [60]. The overwhelming majority of studies with adequate statistical power demonstrate that these missed metastases are prognostically significant, associated with a 10-15% worsening of disease-free survival [60,61,62]. SLN biopsy for the first time makes enhanced pathologic analysis logistically feasible, and allows the identification of a group of patients whose increased risk of systemic relapse might otherwise go unrecognized. While SLN biopsy is itself subject to a small percentage of false negative results, the proportion of false negatives with a conventional pathologic analysis of the axillary nodes is perhaps 10-fold greater.

A striking parallel to the presented findings arises from two German studies [63,64], in which the bone marrow of breast cancer patients harvested at the time of their surgery was examined for micrometastases using immunohistochemical staining. Both demonstrate, firstly, a strong correlation of micrometastases with stage of disease and, secondly, an 'independent' prognostic significance of bone marrow micrometastases that equals or exceeds that of axillary node status.

Breast cancer is a disease characterized by heterogeneity, and nowhere is this heterogeneity more apparent than at the level of the SLN. Enhanced pathologic analysis using immunohistochemical and serial sections may identify SLN containing single metastatic cells, tiny groups of cells, micrometastatic clusters, or even large macrometastases found on a directed retrospective review of the hematoxylin and eosin stained sections. These gradations suggest that not all nodal metastases are the same, but they rather represent a spectrum of risk, posing a dilemma for the oncologist trying to ascertain the necessity of systemic adjuvant treatment. Even with the maturity of clinical trials now in progress, the prognostic significance of occult SLN metastases will remain a matter of controversy.

Follow-up

The follow-up of patients after SLN biopsy, as for breast cancer patients in general, is for life. While local recurrence has been reported in the regional node basin after SLN biopsy for melanoma [65], no such recurrences have been observed in breast cancer patients after a negative SLN biopsy, either in our experience or that of others [66]. Such recurrences will recur, but we ultimately expect that that the rate of isolated axillary relapse after a negative SLN biopsy will be comparable with that after a conventional axillary dissection, 1% or less. We expect the other long term morbidities of SLN biopsy to also be substantially less than that of axillary dissection, if not zero. Early results from a prospective study of our own patients demonstrate a substantial reduction in postoperative sensory phenomena for SLN biopsy compared with axillary dissection; long term studies also address the relative risk of lymphedema and cellulitis.

Abbreviations

ALND =:

axillary lymph node dissection

FNA =:

fine-needle aspiration

SLN =:

sentinel lymph node.

References

  1. 1.

    Cabanas R: An approach for the treatment of penile carcinoma. Cancer. 1977, 39: 456-466.

  2. 2.

    Morton DL, Wen DR, Wong JH, Economou JS, Cagle LA, Storm FK, Foshag LJ, Cochran AJ: Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992, 127: 392-399.

  3. 3.

    Greenlee RT, Murray T, Bolden S, Wingo P: Cancer statistics, 2000. CA Cancer J Clin. 2000, 50: 7-33.

  4. 4.

    Krag DN, Weaver DL, Alex JC, Fairbank JT: Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol. 1993, 2: 335-340.

  5. 5.

    Veronesi U, Paganelli G, Galimberti V, Viale G, Zurrida S, Bedoni M, Costa A, de Cicco C, Geraghty JG, Luini A, Sacchini V, Veronesi P: Sentinel node biopsy to avoid axillary dissection in breast cancer with clnically negative lymph-nodes. Lancet. 1997, 349: 1864-1867. 10.1016/S0140-6736(97)01004-0.

  6. 6.

    Pijpers R, Meijer S, Hoekstra OS, Collet GJ, Comans EF, Boom RP, van Diest PJ, Teule GJ: Impact of lymphoscintigraphy on sentinel node identification with technetium-99m-colloidal albumin in breast cancer. J Nucl Med. 1997, 38: 366-368.

  7. 7.

    Roumen RMH, Valkenburg JGM, Geuskens LM: Lymphoscintigraphy and feasibility of sentinel node biopsy in 83 patients with primary breast cancer. Eur J Surg Oncol. 1997, 23: 495-502.

  8. 8.

    Galimberti V, Zurrida S, Zucali P, Luini A: Can sentinel node biopsy avoid axillary dissection in clinically node-negative breast cancer patients?. Breast. 1998, 7: 8-10. 10.1016/S0960-9776(98)90043-1.

  9. 9.

    Borgstein PJ, Pijpers R, Comans EF, van Diest PJ, Boom RP, Meijer S: Sentinel lymph node biopsy in breast cancer: guidelines and pitfalls of lymphoscintigraphy and gamma probe detection. J Am Coll Surg. 1998, 186: 275-283. 10.1016/S1072-7515(98)00011-8.

  10. 10.

    Krag D, Weaver D, Ashikaga T, Moffat F, Klimberg VS, Shriver C, Feldman S, Kusminsky R, Gadd M, Kuhn J, Harlow S, Beitsch P: The sentinel node in breast cancer - a multicenter validation study. N Engl J Med. 1998, 339: 941-946. 10.1056/NEJM199810013391401.

  11. 11.

    Crossin JA, Johnson AC, Stewart PB, Turner WW: Gamma-probe-guided resection of the sentinel lymph node in breast cancer. Am Surg. 1998, 64: 666-669.

  12. 12.

    Rubio IT, Kogourian S, Cowan C, Krag DN, Colvert M, Klimberg S: Sentinel lymph node biopsy for staging breast cancer. Am J Surg. 1998, 176: 532-537. 10.1016/S0002-9610(98)00264-5.

  13. 13.

    Gulec SA, Moffat FL, Carroll RG, Serafini AN, Sfakianakis GN, Allen L, Boggs J, Escobedo D, Pruett CS, Gupta A, Livingstone AS, Krag DN: Sentinel lymph node localization in early breast cancer. J Nucl Med. 1998, 39: 1388-1393.

  14. 14.

    Snider H, Dowlatshahi K, Fan M, Bridger WM, Rayudu G, Oleske D: Sentinel node biopsy in the staging of breast cancer. Am J Surg. 1998, 176: 305-310. 10.1016/S0002-9610(98)00207-4.

  15. 15.

    Winchester DJ, Sener SF, Winchester DP, Perlman RM, Gold-schmidt RA, Motykie G, Martz CH, Rabbitt SL, Brenin D, Stull MA, Moulthrop JM: Sentinel lymphadenectomy for breast cancer: experience with 180 consecutive patients: efficacy of filtered technitium 99m sulphur colloid with overnight migration time. J AmColl Surg. 1999, 188: 597-603. 10.1016/S1072-7515(99)00060-5.

  16. 16.

    Feldman SM, Krag DN, McNally RK, Moor BB, Weaver DL, Klein P: Limitation in gamma probe localization of the sentinel node in breast cancer patients with large excisional biopsy. J Am Coll Surg. 1999, 188: 248-254. 10.1016/S1072-7515(98)00306-8.

  17. 17.

    Moffat FL, Gulec SA, Sittler SY, Serafini AN, Sfakianakis GN, Boggs JE, Franceschi D, Pruett CS, Pop R, Gurkok C, Livingstone AS, Krag DN: Unfiltered sulfur colloid and sentinel node biopsy for breast cancer: technical and kinetic considerations. Ann Surg Oncol. 1999, 6: 746-755.

  18. 18.

    Veronesi U, Paganelli G, Viale G, Galimberti V, Luini A, Zurrida S, Robertson C, Sacchini V, Veronesi P, Orvieto E, de Cicco C, Intra M, Tosi G, Scarpa D: Sentinel lymph node biopsy and axillary dissection in breast cancer: results in a large series. J Natl Cancer Inst. 1999, 91: 368-373. 10.1093/jnci/91.4.368.

  19. 19.

    Miner TJ, Shriver CD, Jaques DP, Maniscalco-Theberge ME, Krag DN: Sentinel lymph node biopsy for breast cancer: the role of previous biopsy on patient eligibility. Am Surg. 1999, 65: 493-499.

  20. 20.

    Giuliano AE, Kirgan DM, Guenther JM, Morton DL: Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994, 220: 391-401.

  21. 21.

    Giuliano AE, Jones RC, Brennan M, Statman R: Sentinel lymphadenectomy in breast cancer. J Clin Oncol. 1997, 15: 2345-2350.

  22. 22.

    Guenther JM, Krishnamoorthy M, Tan LR: Sentinel lymphadenectomy for breast cancer in a community managed care setting. Cancer J Sci Am. 1997, 3: 336-3340.

  23. 23.

    Flett MM, Going JJ, Stanton PD, Cooke TG: Sentinel node localization in patients with breast cancer. Br J Surg. 1998, 85: 991-993. 10.1046/j.1365-2168.1998.00746.x.

  24. 24.

    Kapteijn BAE, Nieweg OE, Petersen JL, Rutgers EJTh, Hart AAAM, Kroon BB: Identification and biopsy of the sentinel lymph node in breast cancer. Eur J Surg Oncol. 1998, 24: 427-430.

  25. 25.

    Dale PS, Williams JTIV: Axillary staging using selective sentinel lymphadenectomy for patients with invasive breast carcinoma. Am Surg. 1998, 64: 28-31.

  26. 26.

    Ratanawichtrasin A, Levy L, Myles J, Crowe JP: Experience with lymphatic mapping in breast cancer using isosulfan blue dye. J Womens Health. 1998, 7: 873-877.

  27. 27.

    Imoto S, Hasebe T: Initial experience with sentinel node biopsy in breast cancer at the National Cancer Center Hospital East. Jpn J Clin Oncol. 1999, 29: 11-15. 10.1093/jjco/29.1.11.

  28. 28.

    Kern KA: Sentinel lymph node mapping in breast cancer using subareolar injection of blue dye. J Am Coll Surg. 1999, 189: 539-545. 10.1016/S1072-7515(99)00200-8.

  29. 29.

    Morgan A, Howisey RL, Aldape HC, Patton RG, Rowbotham RK, Schmidt EK, Cimrell CR: Initial experience in a community hospital with sentinel lymph node mapping and biopsy for evaluation of axillary lymph node status in palpable invasive breast cancer. J Surg Oncol. 1999, 72: 24-31. 10.1002/(SICI)1096-9098(199909)72:1<24::AID-JSO6>3.3.CO;2-O.

  30. 30.

    Morrow M, Rademaker AW, Bethke KP, Talamonti MS, Dawes LG, Clauson J, Hansen N: Learning sentinel node biopsy: results of a prospective randomized trial of two techniques. Surgery. 1999, 126: 714-722. 10.1067/msy.2099.99951b.

  31. 31.

    Albertini JJ, Lyman GH, Cox C, Yeatman T, Balducci L, Ku NN, Shivers S, Berman C, Wells K, Rapaport D, Shons A, Horton J, Greenberg H, Nicosia S, Clark R, Cantor A, Reintgen DS: Lymphatic mapping and sentinel node biopsy in the patient with breast cancer. JAMA. 1996, 276: 1818-1822. 10.1001/jama.276.22.1818.

  32. 32.

    Borgstein PJ, Meijer S, Pijpers R: Intradermal blue dye to identify sentinel lymph node in breast cancer. Lancet. 1997, 349: 1668-1669.

  33. 33.

    O'Hea BJ, Hill ADK, El-Shirbiny A, Yeh SDJ, Rosen PP, Coit DG, Borgen PI, Cody HS: Sentinel lymph node biopsy in breast cancer: initial experience at Memorial Sloan-Kettering Cancer Center. J Am Coll Surg. 1998, 186: 423-427. 10.1016/S1072-7515(98)00060-X.

  34. 34.

    Barnwell JM, Arredondo MA, Kollmorgen D, Gibbs JF, Lamonica D, Carson W, Zhang P, Winston J, Edge SB: Sentinel node biopsy in breast cancer. Ann Surg Oncol. 1998, 5: 126-130.

  35. 35.

    de Cicco C, Chinol M, Paganelli G: Intraoperative localization of the sentinel node in breast cancer: technical aspects of lymphoscintigraphic methods. Semin Surg Oncol. 1998, 15: 268-271. 10.1002/(SICI)1098-2388(199812)15:4<268::AID-SSU16>3.0.CO;2-I.

  36. 36.

    Czerniecki BJ, Scheff AM, Callans LS, Spitz FR, Bedrosian I, Conant EF, Orel SG, Berlin J, Helsabek C, Fraker DL, Reynolds C: Immunohistochemistry with pancytokeratins improves the sensitivity of sentinel lymph node biopsy in patients with breast carcinoma. Cancer. 1999, 85: 1098-1103. 10.1002/(SICI)1097-0142(19990301)85:5<1098::AID-CNCR13>3.0.CO;2-N.

  37. 37.

    Van der Ent FWC, Kengen RAM, van der Pol HAG, Hoofwijk AGM: Sentinel node biopsy in 70 unselected patients with breast cancer: increased feasibility using 10 mCi radiocolloid in combination with blue dye tracer. Eur J Surg Oncol. 1999, 25: 24-29. 10.1053/ejso.1998.0594.

  38. 38.

    Schneebaum S, Stadler J, Cohen M, Yaniv D, Baron J, Skornick Y: Gamma probe-guided sentinel node biopsy — optimal timing for injection. Eur J Surg Oncol. 1998, 24: 515-519.

  39. 39.

    Bass SS, Cox CE, Ku NN, Berman C, Reintgen DS: The role of sentinel lymph node biopsy in breast cancer. J Am Coll Surg. 1999, 189: 183-194. 10.1016/S1072-7515(99)00130-1.

  40. 40.

    Burak WE, Walker MJ, Yee LD, Kim JA, Saha S, Hinkle G, Olsen JO, Pozderac R, Farrar WB: Routine preoperative lymphoscintigraphy is not necessary prior to sentinel node biopsy for breast cancer. Am J Surg. 1999, 177: 445-449. 10.1016/S0002-9610(99)00088-4.

  41. 41.

    Nwariaku FE, Euhus DM, Beitsch PD, Clifford E, Erdman W, Mathews D, Albores-Saavedra J, Leitch MA, Peters GN: Sentinel lymph node biopsy, an alternative to elective axillary dissection for breast cancer. Am J Surg. 1998, 176: 529-531. 10.1016/S0002-9610(98)00276-1.

  42. 42.

    Jaderborg JM, Harrison PB, Kiser JL, Maynard SL: The feasibility and accuracy of sentinel lymph node biopsy for breast carcinoma. Am Surg. 1999, 65: 699-705.

  43. 43.

    Cody HS, Borgen PI: State-of-the-art approaches to sentinel node biopsy for breast cancer: study design, patient selection, technique, and quality control at Memorial Sloan-Kettering Cancer Center. Surg Oncol. 1999, 8: 85-91. 10.1016/S0960-7404(99)00029-8.

  44. 44.

    Cody HS, Hill ADK, Tran KN, Brennan MF, Borgen PI: Credentialing for breast lymphatic mapping — how many cases are enough?. Ann Surg. 1999, 229: 723-728. 10.1097/00000658-199905000-00015.

  45. 45.

    Cox CE, Bass SS, Boulware D, Ku NN, Berman C, Reintgen DS: Implementation of new surgical technology: outcome measures for lymphatic mapping of breast carcinoma. Ann Surg Oncol. 1999, 6: 553-561.

  46. 46.

    McMasters KM, Tuttle TM, Carlson DJ, Brown CM, Noyes RD, Glaser RL, Vennekotter DJ, Turk PS, Tate PS, Sardi A, Cerrito PB, Edwards MJ: Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used. J Clin Oncol. 2000, 18: 2560-2566.

  47. 47.

    Hill ADK, Tran KN, Akhurst T, Yeung H, Yeh SDJ, Rosen PP, Borgen PI, Cody HS: Lessons learned from 500 cases of lymphatic mapping for breast cancer. Ann Surg. 1999, 229: 528-535. 10.1097/00000658-199904000-00012.

  48. 48.

    Cody HS, Akhurst T, Fazzari M, Fey J, Mazumdar M, Yeung H, Yeh SDJ, Borgen PI: Complementarity of blue dye and isotope in sentinel node localization for breast cancer: univariate and multivariate analysis of 970 procedures. SSO Abstracts. 2000

  49. 49.

    Klauber-DeMore N, Tan LK, Liberman L, Kaptain S, Fey J, Borgen PI, Heerdt AS, Montgomery LL, Paglia M, Petrek JA, Cody HS, VanZee KJ: Sentinel lymph node biopsy: is it indicated in patients with high-risk DCIS or of DCIS with microinvasion?. Ann Surg Oncol. 2000, 7: 636-642.

  50. 50.

    Liberman L, Cody HS, Hill ADK, Yeh SDJ, Rosen PP, Borgen PI, Morris EA, Abramson AF, Dershaw DD: Sentinel lymph node biopsy after percutaneous diagnosis of nonpalpable breast cancer. Radiology. 1999, 211: 835-844.

  51. 51.

    Olson JA, Fey J, Winawer J, Borgen PI, Cody HS, Van Zee KJ, Petrek J, Heerdt AS: Sentinel lymphadenectomy is indicated for T2 breast cancer. J Am Coll Surg. 2000, 191: 593-599. 10.1016/S1072-7515(00)00732-8.

  52. 52.

    Bedrosian I, Reynolds C, Mick R, Callans LS, Grant CS, Donohue JH, Farley DR, Heller R, Conant E, Orel SG, Lawton TJ, Fraker DL, Czerniecki BJ: Accuracy of sentinel lymph node biopsy in patients with large primary breast tumors. Cancer. 2000, 88: 2540-2545. 10.1002/1097-0142(20000601)88:11<2540::AID-CNCR16>3.3.CO;2-1.

  53. 53.

    Kuerer HM, Sahin AA, Hunt KK, Newman LA, Breslin TM, Ames FC, Ross MI, Buzdar AU, Hortobagyi GN, Singletary E: Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Ann Surg. 1999, 230: 72-78. 10.1097/00000658-199907000-00011.

  54. 54.

    Linehan DC, Hill ADK, Akhurst T, Tran KN, Borgen PI, Cody HS: Intradermal radiocolloid and intraparenchymal blue dye injection optimize sentinel node identification in breast cancer patients. Ann Surg Oncol. 1999, 6: 450-454.

  55. 55.

    Boolbol SK, Fey J, Borgen PI, Heerdt AS, Montgomery L, Paglia M, Petrek JA, Cody HS, Van Zee KJ: Intradermal isotope injection: a highly accurate method of lymphatic mapping in breast carcinoma. Ann Surg Oncol. 2001, 8: 20-24. 10.1245/aso.2001.8.1.20.

  56. 56.

    Borgstein PJ, Meijer S, Pijpers R, van Diest PJ: Functional lymphatic anatomy for sentinel node biopsy in breast cancer; echoes from the past and the periareolar blue dye method. Ann Surg. 2000, 232: 81-89. 10.1097/00000658-200007000-00012.

  57. 57.

    Linehan DC, Hill ADK, Tran KN, Yeung H, Yeh SDJ, Borgen PI, Cody HS: Sentinel lymph node biopsy in breast cancer: unfiltered radioisotope is superior to filtered. J Am Coll Surg. 1999, 188: 377-381. 10.1016/S1072-7515(98)00314-7.

  58. 58.

    Jansen L, Doting MH, Rutgers EJ, de Vries J, Olmos RA, Nieweg OE: Clinical relevance of sentinel lymph nodes outside the axilla in patients with breast cancer. Br J Surg. 2000, 87: 920-925. 10.1046/j.1365-2168.2000.01437.x.

  59. 59.

    Weiser MR, Montgomery LL, Susnik B, Borgen PI, Cody HS: Is routine intraoperative frozen section of sentinel lymph nodes in breast cancer patients worthwhile?. Ann Surg Oncol. 2000, 7: 651-655.

  60. 60.

    Dowlatshahi K, Fan M, Snider HC, Habib FA: Lymph node micrometastases from breast carcinoma: reviewing the dilemma. Cancer. 1997, 80: 1188-1197. 10.1002/(SICI)1097-0142(19971001)80:7<1188::AID-CNCR2>3.0.CO;2-H.

  61. 61.

    International (Ludwig) Breast Cancer Study Group: Prognostic importance of occult axillary lymph node micrometastases from breast cancers. Lancet. 1990, 335: 1565-1568. 10.1016/0140-6736(90)91386-O.

  62. 62.

    Cote RJ, Peterson HF, Chaiwun B, Gelber RD, Goldhirsch A, Castiglione-Gertsch M, Gusterson B, Neville AM: Role of immunohistochemical detection of lymph-node metastases in management of breast cancer. International Breast Cancer Study Group. Lancet. 1999, 354: 896-900. 10.1016/S0140-6736(98)11104-2.

  63. 63.

    Diel IJ, Kaufmann M, Costa SD, Holle R, von Minckwitz G, Solomayer EF, Kaul S, Bastert G: Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status. JNCI. 1996, 88: 1652-1664. 10.1093/jnci/88.22.1652.

  64. 64.

    Braun S, Pantel K, Muller P, Janni W, Hepp F, Kentenich CRKMGS, Wischnik A, Dimpfl T, Kindermann G, Riethmuller G, Schlimok G: Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N Eng J Med. 2000, 342: 525-533. 10.1056/NEJM200002243420801.

  65. 65.

    Gershenwald JE, Colome MI, Lee JE, Mansfield PF, Tseng C, Lee JJ, Balch CM, Ross MI: Patterns of recurrence following a negative sentinel lymph node biopsy in 243 patients with stage I or II melanoma. J Clin Oncol. 1998, 16: 2253-2260.

  66. 66.

    Giuliano AE, Haigh PI, Brennan M, Hansen NM, Kelley MC, Ye W, Glass EC, Turner RR: Prospective observational study of sentinel lymphadenectomy without further axillary dissection in patients with sentinel node-negative breast cancer. J Clin Oncol. 2000, 18: 2553-2559.

Download references

Author information

Correspondence to Hiram S Cody III.

Rights and permissions

Reprints and Permissions

About this article

Keywords

  • breast cancer
  • lymph node metastasis
  • lymphoscintigraphy
  • sentinel node