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NLN NATIONAL LYMPHEDEMA NETWORK LYMPHLink Article Reprint Vol 23 No 4 October - December 2011 RESEARCH PERSPECTIVE Advances in the surgical treatment of breast cancer: Can the risk of lymphedema be reduced? Sentinel lymph node biopsy and Axillary Reverse Mapping By: Janice N. Cormier, MD, MPH, Kate Cromwell, MS, Sheila Ridner, PhD, RN, FAAN S entinel lymph node biopsy (SLNB) has been the standard of care for the assessment of lymph node metastases in breast cancer patients since the 1990s.1 Sentinel lymph node mapping is a technique in which the region surrounding a patient’s primary breast tumor is injected with a traceable blue dye (e.g., isosulfan blue) and/or a radioisotope (e.g., technetium-labeled sulfur colloid). The tracer then travels through the lymphatic system to the regional lymph node basin to identify the first tumor-draining lymph node(s), the sentinel node(s). Sentinel nodes are identified using a probe to detect the radioactive tracer within the node and/or by direct visualization of a blue sentinel node through a small surgical incision.2 The identification, excision, and pathologic assessment of the sentinel node(s), which together is called a SLNB, is a commonly performed surgical procedure that has been shown to be highly effective in detecting micrometastatic disease in breast cancer patients.2 Patients whose nodes test negative for disease or have minimal metastatic disease can be spared a complete axillary node dissection.3 While SLNB has been shown to reduce the likelihood of lymphedema compared with axillary lymph node dissection, SLNB does not completely eliminate the risk of lymphedema.4-11 An evaluation of lymphedema studies from 2000 to 2007 revealed that 253 (about 6%) of 4,241 patients who had undergone SLNB subsequently developed lymphedema.4-11 With an estimated 207,090 cases of breast cancer diagnosed in 2010 and 20% to 30% of these patients requiring SLNB, as many as 3,700 could develop lymphedema. Axillary reverse mapping (ARM) was recently introduced as a procedure for identifying upper extremity lymphatics so surgeons can preserve them at the time of axillary lymph node dissection or SLNB in order to potentially reduce the risk of postsurgical lymphedema.13-15 During ARM, blue dye is injected in the ipsilateral (same side) upper inner arm along the intramuscular groove,16 travels in the lymphatics to the axilla, and serves to identify the lymphatic channels of the arm. It is believed that the identification of the upper extremity lymph nodes is possible because of the anatomic variation of the lymphatics of the upper extremity and breast.13 The ARM procedure was first evaluated by Klimberg et al.; during this evaluation, an initial group of 18 patients underwent the ARM procedure with the injection of 2.5 to 5.0 mL of isosulfan blue dye in the upper inner arm at the time of axillary lymph node dissection.14 In a subsequent group of patients undergoing SLNB, with radioactive tracer used to inject the tumor site and blue dye used to identify ARM nodes, only 3% of blue nodes contained radioactive tracer (from SNLB)17 and metastases were not detected in any of the blue ARM nodes. This is important because tumor involved nodes should not be left behind during the SLNB staging procedure even if they are demonstrated to also drain lymphatics from the upper extremity. However, while the feasibility of the ARM procedure has been demonstrated in several small studies,1, 14, 16, 18, 19 the efficacy of ARM and its reduction of the incidence of lymphedema have yet to be confirmed. More recent ARM studies have reported the identification of metastatic disease in up to 18% of the blue (ARM) lymph nodes which if preserved may lead to disease progression.18, 20 These results call into question the oncologic safety of the ARM technique. Studies evaluating ARM at the time of SLNB have had similar findings; a concordance between SLNB radioactive lymph nodes and ARM blue nodes of 18.9%, with one-third of those nodes containing metastases.21 Most studies report that ARM can identify lymphatics and nodes in 60% to 88% of patients. Other studies indicate that despite the identification of the nodes and/or lymphatics by ARM, it is not always possible to preserve these lymphatics.22 An additional problem with the technique is that some patients have reported temporary blue tattooing of the injection site, which has lasted from a few days to several months.16 Most importantly, the ARM technique has not been longitudinally studied with objective extremity measures; therefore the primary National Lymphedema Network, Inc. • 116 New Montgomery St., Suite 235 • San Francisco, CA 94105 Infoline: 1-800-541.3259 • Tel: 415-908-3681 • Fax: 415-908-3813 • Email: [email protected] • Website: www.lymphnet.org PAGE 1 OF 2 ARM-related benefit associated with a proposed reduction in the incidence of lymphedema has yet to be determined.18 For patients with breast cancer, SLNB has been shown to be a highly accurate staging procedure that reduces but does not eliminate the risk of lymphedema compared with axillary node dissection. However, given the annual incidence of breast cancer and the frequency with which SLNB is performed, even a small risk translates into thousands of women developing lymph-edema. These figures have prompted clinicians to investigate additional techniques such as the ARM procedure for lymphatic preservation.14 Although there is not sufficient evidence for the widespread adoption of ARM, further study is warranted to determine its safety, efficacy, and long-term benefits. 1.Noguchi M, Yokoi M, Nakano Y. Axillary reverse mapping with indocyanine fluorescence imaging in patients with breast cancer. J Surg Oncol; 101(3):217-21. 2.O’Hea BJ, Hill AD, El-Shirbiny AM, et al. Sentinel lymph node biopsy in breast cancer: initial experience at Memorial SloanKettering Cancer Center. J Am Coll Surg 1998; 186(4):423-7. 3.Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA 2011; 305(6):569-75. 4.Noguchi M. Axillary reverse mapping for breast cancer. Breast Cancer Res Treat 2009; 119(3):529-35. 5.Langer I, Guller U, Berclaz G, et al. Morbidity of sentinel lymph node biopsy (SLN) alone versus SLN and completion axillary lymph node dissection after breast cancer surgery: a prospective Swiss multicenter study on 659 patients. Ann Surg 2007; 245(3):452-61. 6.Mansel RE, Fallowfield L, Kissin M, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst 2006; 98(9):599-609. 7.Francis WP, Abghari P, Du W, et al. Improving surgical outcomes: standardizing the reporting of incidence and severity of acute lymphedema after sentinel lymph node biopsy and axillary lymph node dissection. Am J Surg 2006; 192(5):636-9. 8.Wilke LG, McCall LM, Posther KE, et al. Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial. Ann Surg Oncol 2006; 13(4):491-500. 9.Lucci A. Re: Clinical implications of sentinel nodes outside the axilla and internal mammary chain in patients with breast cancer, by van Rijk MC, Tanis PJ, Nieweg OE, et al. J Surg Oncol 2006; 94(4):266-8. 10.Purushotham AD, Upponi S, Klevesath MB, et al. Morbidity after sentinel lymph node biopsy in primary breast cancer: results from a randomized controlled trial. J Clin Oncol 2005; 23(19):4312-21. 11.Leidenius MH. Sentinel node biopsy in breast cancer. Acta Radiol 2005; 46(8):791-801. 12.Howlader N, Noone A, Krapcho M, et al. SEER cancer statistics review, 1975-2008. In Institute NC, ed., Vol. 2011. Bethesda, MD: SEER, 2011. 13.Noguchi M. Axillary reverse mapping for preventing lymphedema in axillary lymph node dissection and/or sentinel lymph node biopsy. Breast Cancer; 17(3):155-7. 14.Klimberg VS. A new concept toward the prevention of lymphedema: axillary reverse mapping. J Surg Oncol 2008; 97(7):563-4. 15.Toi M, Winer EP, Inamoto T, et al. Identifying Gaps in the Locoregional Management of Early Breast Cancer: Highlights from the Kyoto Consensus Conference. Ann Surg Oncol 2011. 16.Boneti C, Korourian S, Diaz Z, et al. Scientific Impact Award: Axillary reverse mapping (ARM) to identify and protect lymphatics draining the arm during axillary lymphadenectomy. Am J Surg 2009; 198(4):482-7. 17.Boneti C, Korourian S, Bland K, et al. Axillary reverse mapping: mapping and preserving arm lymphatics may be important in preventing lymphedema during sentinel lymph node biopsy. J Am Coll Surg 2008; 206(5):1038-42; discussion 1042-4. 18.Bedrosian I, Babiera GV, Mittendorf EA, et al. A phase I study to assess the feasibility and oncologic safety of axillary reverse mapping in breast cancer patients. Cancer 2010; 116(11):2543-8. PAGE 2 OF 2 19.Thompson M, Korourian S, Henry-Tillman R, et al. Axillary reverse mapping (ARM): a new concept to identify and enhance lymphatic preservation. Ann Surg Oncol 2007; 14(6):1890-5. 20.Nos C, Kaufmann G, Clough KB, et al. Combined axillary reverse mapping (ARM) technique for breast cancer patients requiring axillary dissection. Ann Surg Oncol 2008; 15(9):2550-5. 21.Kang SH, Choi JE, Jeon YS, al. E. Preservation of lymphatic drainage from arm in breast cancer surgery: is it safe? San Antonio Breast Cancer Symposium. San Antonio, Texas, 2008. 22.Casabona F, Bogliolo S, Valenzano Menada M, et al. Feasibility of axillary reverse mapping during sentinel lymph node biopsy in breast cancer patients. Ann Surg Oncol 2009; 16(9):2459-63. University of Texas MD Anderson Cancer Center, Houston, TX Vanderbilt University School of Nursing [email protected]