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Predictors of Tumour Involvement in Remaining Axillary Lymph Nodes of Breast Cancer Patients With Positive Sentinel Lymph Node
were randomly assigned to undergo either sentinel lymph node biopsy or standard axillary surgery in this study. The authors examined multiple outcome measures, including the standard complications of axillary surgery such as lymphedema and sensory loss. Quality of life and arm functioning scores were also assessed in both groups. As one might expect, moderate or severe lymphedema was self-reported more often by patients in the standard axillary treatment group than by patients in the sentinel lymph node biopsy group at all time points after surgery. However, when objective circumferential measurements of the upper arm and forearm were taken, there was no statistically significant difference between the sentinel lymph node biopsy group and the standard axillary treatment group at 1 year after surgery. This finding has several possible explanations. Because this was an intention-to-treat analysis, 17% of the patients in the sentinel lymph node biopsy group underwent complete axillary clearance. It is quite possible that lymphedema may not occur until a longer time interval has passed from operative therapy, and 12 months may not have been enough
time to identify significant differences in arm circumference. Another possibility is that axillary lymph node dissection induces less arm swelling than previously thought, and there is a concomitant and real risk of arm swelling with sentinel lymph node biopsy. In any case, this is the second multicenter prospective randomized study (the American College of Surgeons Oncology Group Z0010 study1 was the other) to report an incidence of lymphedema of at least 5% after sentinel lymph node biopsy. In the current study, patient selfreported arm numbness or sensory deficit was common after standard axillary dissection but not after sentinel lymph node biopsy, as one would expect. Consistent with the reports of subjectively better scores for lymphedema and numbness in the sentinel lymph node biopsy group, quality-of-life instruments showed better scores at all time points after sentinel lymph node biopsy than standard axillary treatment. Furthermore, patients who underwent sentinel lymph node biopsy returned to normal activities sooner than patients who underwent standard axillary dissection. The ALMANAC study documents a better outcome and lower morbidity for
sentinel lymph node biopsy than standard axillary dissection. The authors hypothesize that these findings should translate not only into improved outcomes (and improved quality of life) for patients with breast cancer but that sentinel lymph node biopsy should reduce overall health care costs. They postulate that shorter hospital stays, faster return to normal activity, and lower morbidity from the procedure will reduce the overall health care costs of the patient with breast cancer. Documented reports of lower morbidity, better quality of life, and likely lower health care costs all support the use of sentinel lymph node biopsy as the preferred means of axillary staging for most patients with earlystage breast cancer and clinically negative axillary nodes. A. Lucci, Jr, MD
Reference 1. 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 13:491-500, 2006.
ANNOTATED BIBLIOGRAPHY Predictors of Tumour Involvement in Remaining Axillary Lymph Nodes of Breast Cancer Patients With Positive Sentinel Lymph Node Wada N, Imoto S, Yamauchi C, et al Eur J Cancer Surg 32:29-33, 2006 Wada and colleagues did a masterful job at reviewing their data and provide an excellent literature review on the topic of the predictive value of non-sentinel lymph node (NSLN) involvement. I agree with their conclusion that although they found 4 independent factors (primary tumor size, size of sentinel lymph node me-
182 182
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Breast Diseases: A Year Book Quarterly Vol 18 No 2 2007
tastasis, 100% involvement of all sentinel lymph nodes, and lymphovascular invasion) to be predictive of NSLN metastasis, it does not seem that even the combination of these factors is enough to justify omitting axillary lymph node dissection (ALND) safely. Of interest in the review of their data is the significant falsenegative rate of 25.4% in their first 160 patients for whom a complete ALND was performed, which was not calculated in the analysis of additional positive NSLN disease. Because the role of the surgeon is to achieve local control to the axilla and breast and to accurately stage the disease, it seems intuitive that every attempt be made surgically to achieve those end points. The exhaustive review of all the works done to determine
which patients do not need ALND when the SLN is positive seems counterintuitive to these goals. Even when the maximal statistical probability is that an additional NSLN would be negative, the fact of the matter is that this number has never been predicted much below the 6% threshold—except perhaps in the rare example of the 80+ year old with a grade 1 tubular carcinoma smaller than 1 cm that is nonpalpable on examination with no lymphovascular invasion1-2— and the number is still a 5% risk that additional nodes may be detected with disease. Furthermore, in this example, the information would be known in most cases only after a retrospective case analysis. Clearly, we have truly eliminated the need for complete ALND in 70% of all patients, thus improving their outcome and reducing the risk of axillary recurrence 10-fold, as seen in the era of routine complete ALND by performing a SLN biopsy and an immunohistochemical analysis. Indeed, the old adage “you can never make your mark in the surgical arena unless you do too little or too much surgery” seems to apply and to be the impetus for this hair-splitting routine to decide who else can be spared the additional removal of the axillary lymph nodes. A noncompromising position for complete ALND is to ensure the safety of the patient by surgically achieving maximal local control, thus greatly reducing long-term morbidity for those in whom the disease will eventually recur in the axillary basin while providing the benefit of accurate staging for adjuvant therapy. In effect, a complete ALND for all patients with a positive SLN would eliminate the risk in 30% of patients of an almost certain long-term axillary recurrence with its attendant complete ALND, radiation therapy, and lymphedema while subjecting the same group to an expectation of a 5% to 15% incidence of lymphedema—a net benefit of 2- to 6-fold over risk. C. E. Cox, MD
References
breast cancer. Sentinel lymph node biopsy (SLNB) accurately stages the axilla and, for the most part, has replaced traditional staging of axillary lymph node dissection. The choice and route of the injectable is variable and also surgeondependent. Initially, animal studies had demonstrated that methylene blue was unsuccessful as it was poorly taken up by the lymphatic system.1 However, albumin-bound isosulfan blue was readily taken up and retained by the lymphatic system. With the shortage of isosulfan blue, the use of methylene blue was re-studied, and Blessing and colleagues2 showed that methylene blue with radioisotope was equivalent to isosulfan blue with radioisotope. The route of injection has also been debated. Klimberg and colleagues3 were able to demonstrate that subareolar injection of technetium drained to the same lymph node as a peritumoral injection of blue dye. Layeeque and colleagues4 have also shown that the subareolar technique can be used for patients with multiple breast cancers, because cancers from different quadrants of the breast are likely to drain to the same SLN. As we strive for the ideal procedure that is the most accurate and associated with the least complications and morbidity, we continue to refine our technique of SLN mapping. Golshan and colleagues were able to demonstrate that methylene blue alone is indeed highly sensitive and can be used for SLN mapping. M. E. G. Thompson, MD R. S. Henry-Tillman, MD
References 1. Wong J, Cagle L, Morton D: Lymphatic drainage of the skin to a sentinel lymph node in a feline model. Ann Surg 214:637-641, 1991.
1. Jakub JW, Ebert MD, Diaz NM, et al: The effect of lymphatic mapping on diagnosis and treatment of patients with T1a, T1b favorable breast cancer. Ann Surg 237:838-843, 2003.
2. Blessing WD, Stolier AJ, Teng SC, et al: Comparison of methylene blue and isosulfan blue dyes for sentinel node mapping in breast cancer: A trial born out of necessity. Am J Surg 184:341345, 2002.
2. Silverstein MJ, Skinner KA, Lomis TJ, et al: Predicting axillary nodal positivity in 2282 patients with breast carcinoma. World J Surg 25:767-772, 2001.
3. Klimberg VS, Rubio IT, Henry R, et al: Subareolar versus peritumoral injection for location of the sentinel lymph node. Ann Surg 229:860-864, 1999.
Can Methylene Blue Only Be Used in Sentinel Lymph Node Biopsy for Breast Cancer?
4. Layeeque R, Henry-Tillman R, Korourian S, et al: Subareolar sentinel node biopsy for multiple breast cancers. Am J Surg 186:730-735, 2003.
Golshan M, Nakhlis F Breast J 127:428-430, 2006 The status of the axillary lymph node is the most important prognostic variable on which to base therapeutic decisions for patients with
®
Breast Diseases: A Year Book Quarterly Vol 18 No 2 2007
183 183
time to identify significant differences in arm circumference. Another possibility is that axillary lymph node dissection induces less arm swelling than previously thought, and there is a concomitant and real risk of arm swelling with sentinel lymph node biopsy. In any case, this is the second multicenter prospective randomized study (the American College of Surgeons Oncology Group Z0010 study1 was the other) to report an incidence of lymphedema of at least 5% after sentinel lymph node biopsy. In the current study, patient selfreported arm numbness or sensory deficit was common after standard axillary dissection but not after sentinel lymph node biopsy, as one would expect. Consistent with the reports of subjectively better scores for lymphedema and numbness in the sentinel lymph node biopsy group, quality-of-life instruments showed better scores at all time points after sentinel lymph node biopsy than standard axillary treatment. Furthermore, patients who underwent sentinel lymph node biopsy returned to normal activities sooner than patients who underwent standard axillary dissection. The ALMANAC study documents a better outcome and lower morbidity for
sentinel lymph node biopsy than standard axillary dissection. The authors hypothesize that these findings should translate not only into improved outcomes (and improved quality of life) for patients with breast cancer but that sentinel lymph node biopsy should reduce overall health care costs. They postulate that shorter hospital stays, faster return to normal activity, and lower morbidity from the procedure will reduce the overall health care costs of the patient with breast cancer. Documented reports of lower morbidity, better quality of life, and likely lower health care costs all support the use of sentinel lymph node biopsy as the preferred means of axillary staging for most patients with earlystage breast cancer and clinically negative axillary nodes. A. Lucci, Jr, MD
Reference 1. 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 13:491-500, 2006.
ANNOTATED BIBLIOGRAPHY Predictors of Tumour Involvement in Remaining Axillary Lymph Nodes of Breast Cancer Patients With Positive Sentinel Lymph Node Wada N, Imoto S, Yamauchi C, et al Eur J Cancer Surg 32:29-33, 2006 Wada and colleagues did a masterful job at reviewing their data and provide an excellent literature review on the topic of the predictive value of non-sentinel lymph node (NSLN) involvement. I agree with their conclusion that although they found 4 independent factors (primary tumor size, size of sentinel lymph node me-
182 182
®
Breast Diseases: A Year Book Quarterly Vol 18 No 2 2007
tastasis, 100% involvement of all sentinel lymph nodes, and lymphovascular invasion) to be predictive of NSLN metastasis, it does not seem that even the combination of these factors is enough to justify omitting axillary lymph node dissection (ALND) safely. Of interest in the review of their data is the significant falsenegative rate of 25.4% in their first 160 patients for whom a complete ALND was performed, which was not calculated in the analysis of additional positive NSLN disease. Because the role of the surgeon is to achieve local control to the axilla and breast and to accurately stage the disease, it seems intuitive that every attempt be made surgically to achieve those end points. The exhaustive review of all the works done to determine
which patients do not need ALND when the SLN is positive seems counterintuitive to these goals. Even when the maximal statistical probability is that an additional NSLN would be negative, the fact of the matter is that this number has never been predicted much below the 6% threshold—except perhaps in the rare example of the 80+ year old with a grade 1 tubular carcinoma smaller than 1 cm that is nonpalpable on examination with no lymphovascular invasion1-2— and the number is still a 5% risk that additional nodes may be detected with disease. Furthermore, in this example, the information would be known in most cases only after a retrospective case analysis. Clearly, we have truly eliminated the need for complete ALND in 70% of all patients, thus improving their outcome and reducing the risk of axillary recurrence 10-fold, as seen in the era of routine complete ALND by performing a SLN biopsy and an immunohistochemical analysis. Indeed, the old adage “you can never make your mark in the surgical arena unless you do too little or too much surgery” seems to apply and to be the impetus for this hair-splitting routine to decide who else can be spared the additional removal of the axillary lymph nodes. A noncompromising position for complete ALND is to ensure the safety of the patient by surgically achieving maximal local control, thus greatly reducing long-term morbidity for those in whom the disease will eventually recur in the axillary basin while providing the benefit of accurate staging for adjuvant therapy. In effect, a complete ALND for all patients with a positive SLN would eliminate the risk in 30% of patients of an almost certain long-term axillary recurrence with its attendant complete ALND, radiation therapy, and lymphedema while subjecting the same group to an expectation of a 5% to 15% incidence of lymphedema—a net benefit of 2- to 6-fold over risk. C. E. Cox, MD
References
breast cancer. Sentinel lymph node biopsy (SLNB) accurately stages the axilla and, for the most part, has replaced traditional staging of axillary lymph node dissection. The choice and route of the injectable is variable and also surgeondependent. Initially, animal studies had demonstrated that methylene blue was unsuccessful as it was poorly taken up by the lymphatic system.1 However, albumin-bound isosulfan blue was readily taken up and retained by the lymphatic system. With the shortage of isosulfan blue, the use of methylene blue was re-studied, and Blessing and colleagues2 showed that methylene blue with radioisotope was equivalent to isosulfan blue with radioisotope. The route of injection has also been debated. Klimberg and colleagues3 were able to demonstrate that subareolar injection of technetium drained to the same lymph node as a peritumoral injection of blue dye. Layeeque and colleagues4 have also shown that the subareolar technique can be used for patients with multiple breast cancers, because cancers from different quadrants of the breast are likely to drain to the same SLN. As we strive for the ideal procedure that is the most accurate and associated with the least complications and morbidity, we continue to refine our technique of SLN mapping. Golshan and colleagues were able to demonstrate that methylene blue alone is indeed highly sensitive and can be used for SLN mapping. M. E. G. Thompson, MD R. S. Henry-Tillman, MD
References 1. Wong J, Cagle L, Morton D: Lymphatic drainage of the skin to a sentinel lymph node in a feline model. Ann Surg 214:637-641, 1991.
1. Jakub JW, Ebert MD, Diaz NM, et al: The effect of lymphatic mapping on diagnosis and treatment of patients with T1a, T1b favorable breast cancer. Ann Surg 237:838-843, 2003.
2. Blessing WD, Stolier AJ, Teng SC, et al: Comparison of methylene blue and isosulfan blue dyes for sentinel node mapping in breast cancer: A trial born out of necessity. Am J Surg 184:341345, 2002.
2. Silverstein MJ, Skinner KA, Lomis TJ, et al: Predicting axillary nodal positivity in 2282 patients with breast carcinoma. World J Surg 25:767-772, 2001.
3. Klimberg VS, Rubio IT, Henry R, et al: Subareolar versus peritumoral injection for location of the sentinel lymph node. Ann Surg 229:860-864, 1999.
Can Methylene Blue Only Be Used in Sentinel Lymph Node Biopsy for Breast Cancer?
4. Layeeque R, Henry-Tillman R, Korourian S, et al: Subareolar sentinel node biopsy for multiple breast cancers. Am J Surg 186:730-735, 2003.
Golshan M, Nakhlis F Breast J 127:428-430, 2006 The status of the axillary lymph node is the most important prognostic variable on which to base therapeutic decisions for patients with
®
Breast Diseases: A Year Book Quarterly Vol 18 No 2 2007
183 183