- Email: [email protected]
Axillary Reverse Mapping: A Prospective Study in Women with Clinically Node Negative and Node Positive Breast Cancer
consistent with the multiple retrospective reports of clinical series showing the benefit of resecting the primary tumor in select patients. In a recent report from The University of Texas MD Anderson Cancer Center1 evaluating 208 patients with stage IV breast cancer and an intact primary tumor, including 74 patients who underwent resection of their primary tumor, investigators reported that surgery was associated with improved overall survival. On multivariable analysis, having only a single focus of metastatic disease (ie, low overall tumor burden) was associated with improved overall survival. One of the more interesting aspects of the current article is data showing that mice in which the primary tumors were resected had
decreased MDSCs and increased CD4+ and CD8+ T-cells in their spleens. This suggests improved immune function after primary tumor resectiondan observation that requires further study. Although these authors showed that decreasing the overall tumor burden results in improved survival in their mouse model, they correctly pointed out that it would be premature to suggest that their findings should affect clinical decision making. To that end, patients should be encouraged to participate in the ongoing phase III Eastern Cooperative Oncology Group trial (E2108), a multicenter, prospective, randomized trial that will investigate the role of early surgery of the intact primary tumor in patients presenting with stage IV breast cancer.
Additional data regarding the role of surgery will be available from a registry study conducted by the Translational Breast Cancer Research Consortium (TBCRC 013) in which clinical management and outcomes of patients presenting with an intact primary tumor and stage IV breast cancer will be documented.
Axillary Reverse Mapping: A Prospective Study in Women with Clinically Node Negative and Node Positive Breast Cancer
(ALND) (group 1) and 57 ALNDs with/without SLNB (group 2). ARM lymphatics were not preserved if they were a SLN, directly entered a SLN, or were within ALND boundaries during ALND. Results.dSLN with radioisotope alone was successful in 92% of procedures (181 of 197). ARM identification was 47% (73 of 155) in group 1. Criteria were met in 30% (47 of 155) for preservation, and 25% (38 of 155) were preserved. Of those who met preservation criteria, 81% (38 of 47) were preserved. In group 2, ARM identification was 72% (41 of 57); 7 met criteria for preservation and were preserved. Of the ARM nodes, 10% (22 of 212) were SLNs (crossover). ARM nodes contained metastatic disease in one crossover and two nonsentinel ARM nodes in clinically node positive patients with N2/N3 disease. Conclusions.dARM is a feasible technique for identification and preser-
vation of axillary arm lymphatics with an acceptable incidence of SLN crossover. A larger sample size is needed to determine if ARM can reduce the incidence of lymphedema in patients undergoing SLNB alone and to confirm the absence of ARM metastases in clinically node negative patients undergoing ALND.
Connor C, McGinness M, Mammen J, et al (Univ of Kansas Med Ctr, Kansas City) Ann Surg Oncol 20:3303-3307, 2013
Background.dThe primary aim of axillary reverse mapping (ARM) is to prevent lymphedema by preserving arm versus breast axillary lymphatics. Concerns regarding feasibility and oncologic safety have limited the adoption of the technique. This prospective study was undertaken to investigate ARM in clinically node negative and node positive breast cancer patients. Methods.dA total of 184 patients underwent 212 ARM procedures: 155 sentinel lymph node biopsies (SLNB) without axillary lymph node dissection
E. A. Mittendorf, MD, PhD
Reference 1. Lang JE, Tereffe W, Mitchell MP, et al. Primary tumor extirpation in breast cancer patients who present with stage IV disease is associated with improved survival. Ann Surg Oncol. 2013;20:1893-1899.
In this study, Connor and colleagues evaluated the new ARM technique to determine whether vital arm lymphatics can be safely spared during axillary surgery in order to minimize the risk of subsequent lymphedema. Multiple institutions have investigated this technique to determine its feasibility and evaluate the spread of breast cancer to extremity nodes. Connor and colleagues demonstrated that the arm drainage system was identified 54% of the time overall: in 47% of patients undergoing SLNB and 72% of patients
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 1 2014
55
undergoing ALND. The ARM lymphatics were preserved in over 80% of patients (45/54), but preservation was achieved predominantly in the SLNB population (38/45), with only 7 cases preserved when ALND was performed. In studies evaluating ARM, a significant difference in the ability to identify extremity lymphatics has been demonstrated in the setting of SLNB as opposed to ALND, as well as a low crossover rate. This is presumed to be due to the deeper axillary location of the arm lymphatic channels.1 Furthermore, when SLNB is performed and the ARM nodes are also removed, the rate of the arm nodal involvement has been shown to be low, as was demonstrated in the study by Connor and colleagues as well. This would suggest that in the setting of SLNB, extremity lymphatics can be safely spared. Given the low rate of lymphedema after SLNB, it remains unclear how much this added surgical procedure would reduce this risk for patients, and when the ARM nodes are identified in only about half of cases, this further reduces the potential benefit. The conversion from ALND to SLNB was low-lying fruit in the effort to reduce lymphedema, and if further improvement is expected with the addition of ARM, then consistent methods of lymphedema measurement as well as confounding or contributing
factors such as patient characteristics and lymphatic irradiation must be considered. Even incidental irradiation with tangent fields can be controlled by the identification of axillary arm lymphatics.2 All these issues suggest that it may be difficult to ever show a significant lymphedema reduction in the SLNB population. The patients most likely to benefit from the sparing of ARM lymphatics are those requiring ALND. However, these are also the patients most likely to have involvement of the nodes identified by ARM. In this series, the 2 patients with positive ARM nodes both had extensive nodal involvement, which is similar to what other investigators have reported; hence, the use of ARM still may be reasonable in a carefully selected ALND population.3,4 But if the ARM techniques described by these authors and others are to be used, a consistent and higher ARM identification rate must be achieved, similar to what is currently obtained in SLNB. After that has been achieved, a large, well-defined ALND study population needs to be prospectively examined to ensure the safe sparing of ARM-defined lymphatics. Finally, the effect of neoadjuvant chemotherapy on the use of ARM needs further definition. In this study, threefourths of the ALND group and a quarter of the SLNB group received neoadjuvant
chemotherapy. Given the higher possibility of crossover involvement of the axillary arm nodes in patients with more extensive nodal involvement, this population should be analyzed separately from patients receiving de novo surgical management.
Increasing National Mastectomy Rates for the Treatment of Early Stage Breast Cancer
Ann Surg Oncol 20:1436-1443, 2013
256,081 women diagnosed with T1e2 N0e3 M0 breast cancer from 2000 to 2008. We evaluated therapeutic mastectomy rates by the year of diagnosis and performed a multivariable logistic regression analyses to determine predictors of mastectomy as the treatment choice.
Mahmood U, Hanlon AL, Koshy M, et al (Univ of Texas MD Anderson Cancer Ctr, Houston; Univ of Pennsylvania, Philadelphia; Univ of Chicago, IL; et al)
56
Background.dTo study national trends in the mastectomy rate for treatment of early stage breast cancer. Methods.dWe analyzed data from the Surveillance, Epidemiology, and End Results database, including
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 1 2014
I. A. Petersen, MD
References 1. Casabona F, Bogliolo S, Valenzano Menada M, Sala P, Villa G, Ferrero S. Feasibility of axillary reverse mapping during sentinel lymph node biopsy in breast cancer patients. Ann Surg Oncol. 2009;16:2459-2463. 2. Cheville AL, Brinkmann DH, Ward SB, et al. The addition of SPECT/CT lymphoscintigraphy to breast cancer radiation planning spares lymph nodes critical for arm drainage. Int J Radiat Oncol Biol Phys. 2013;85:971-977. 3. 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: 2550-2555. 4. Gobardhan PD, Wijsman JH, van Dalen T, et al. ARM: axillary reverse mapping - the need for selection of patients. Eur J Surg Oncol. 2012;38: 657-661.
decreased MDSCs and increased CD4+ and CD8+ T-cells in their spleens. This suggests improved immune function after primary tumor resectiondan observation that requires further study. Although these authors showed that decreasing the overall tumor burden results in improved survival in their mouse model, they correctly pointed out that it would be premature to suggest that their findings should affect clinical decision making. To that end, patients should be encouraged to participate in the ongoing phase III Eastern Cooperative Oncology Group trial (E2108), a multicenter, prospective, randomized trial that will investigate the role of early surgery of the intact primary tumor in patients presenting with stage IV breast cancer.
Additional data regarding the role of surgery will be available from a registry study conducted by the Translational Breast Cancer Research Consortium (TBCRC 013) in which clinical management and outcomes of patients presenting with an intact primary tumor and stage IV breast cancer will be documented.
Axillary Reverse Mapping: A Prospective Study in Women with Clinically Node Negative and Node Positive Breast Cancer
(ALND) (group 1) and 57 ALNDs with/without SLNB (group 2). ARM lymphatics were not preserved if they were a SLN, directly entered a SLN, or were within ALND boundaries during ALND. Results.dSLN with radioisotope alone was successful in 92% of procedures (181 of 197). ARM identification was 47% (73 of 155) in group 1. Criteria were met in 30% (47 of 155) for preservation, and 25% (38 of 155) were preserved. Of those who met preservation criteria, 81% (38 of 47) were preserved. In group 2, ARM identification was 72% (41 of 57); 7 met criteria for preservation and were preserved. Of the ARM nodes, 10% (22 of 212) were SLNs (crossover). ARM nodes contained metastatic disease in one crossover and two nonsentinel ARM nodes in clinically node positive patients with N2/N3 disease. Conclusions.dARM is a feasible technique for identification and preser-
vation of axillary arm lymphatics with an acceptable incidence of SLN crossover. A larger sample size is needed to determine if ARM can reduce the incidence of lymphedema in patients undergoing SLNB alone and to confirm the absence of ARM metastases in clinically node negative patients undergoing ALND.
Connor C, McGinness M, Mammen J, et al (Univ of Kansas Med Ctr, Kansas City) Ann Surg Oncol 20:3303-3307, 2013
Background.dThe primary aim of axillary reverse mapping (ARM) is to prevent lymphedema by preserving arm versus breast axillary lymphatics. Concerns regarding feasibility and oncologic safety have limited the adoption of the technique. This prospective study was undertaken to investigate ARM in clinically node negative and node positive breast cancer patients. Methods.dA total of 184 patients underwent 212 ARM procedures: 155 sentinel lymph node biopsies (SLNB) without axillary lymph node dissection
E. A. Mittendorf, MD, PhD
Reference 1. Lang JE, Tereffe W, Mitchell MP, et al. Primary tumor extirpation in breast cancer patients who present with stage IV disease is associated with improved survival. Ann Surg Oncol. 2013;20:1893-1899.
In this study, Connor and colleagues evaluated the new ARM technique to determine whether vital arm lymphatics can be safely spared during axillary surgery in order to minimize the risk of subsequent lymphedema. Multiple institutions have investigated this technique to determine its feasibility and evaluate the spread of breast cancer to extremity nodes. Connor and colleagues demonstrated that the arm drainage system was identified 54% of the time overall: in 47% of patients undergoing SLNB and 72% of patients
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 1 2014
55
undergoing ALND. The ARM lymphatics were preserved in over 80% of patients (45/54), but preservation was achieved predominantly in the SLNB population (38/45), with only 7 cases preserved when ALND was performed. In studies evaluating ARM, a significant difference in the ability to identify extremity lymphatics has been demonstrated in the setting of SLNB as opposed to ALND, as well as a low crossover rate. This is presumed to be due to the deeper axillary location of the arm lymphatic channels.1 Furthermore, when SLNB is performed and the ARM nodes are also removed, the rate of the arm nodal involvement has been shown to be low, as was demonstrated in the study by Connor and colleagues as well. This would suggest that in the setting of SLNB, extremity lymphatics can be safely spared. Given the low rate of lymphedema after SLNB, it remains unclear how much this added surgical procedure would reduce this risk for patients, and when the ARM nodes are identified in only about half of cases, this further reduces the potential benefit. The conversion from ALND to SLNB was low-lying fruit in the effort to reduce lymphedema, and if further improvement is expected with the addition of ARM, then consistent methods of lymphedema measurement as well as confounding or contributing
factors such as patient characteristics and lymphatic irradiation must be considered. Even incidental irradiation with tangent fields can be controlled by the identification of axillary arm lymphatics.2 All these issues suggest that it may be difficult to ever show a significant lymphedema reduction in the SLNB population. The patients most likely to benefit from the sparing of ARM lymphatics are those requiring ALND. However, these are also the patients most likely to have involvement of the nodes identified by ARM. In this series, the 2 patients with positive ARM nodes both had extensive nodal involvement, which is similar to what other investigators have reported; hence, the use of ARM still may be reasonable in a carefully selected ALND population.3,4 But if the ARM techniques described by these authors and others are to be used, a consistent and higher ARM identification rate must be achieved, similar to what is currently obtained in SLNB. After that has been achieved, a large, well-defined ALND study population needs to be prospectively examined to ensure the safe sparing of ARM-defined lymphatics. Finally, the effect of neoadjuvant chemotherapy on the use of ARM needs further definition. In this study, threefourths of the ALND group and a quarter of the SLNB group received neoadjuvant
chemotherapy. Given the higher possibility of crossover involvement of the axillary arm nodes in patients with more extensive nodal involvement, this population should be analyzed separately from patients receiving de novo surgical management.
Increasing National Mastectomy Rates for the Treatment of Early Stage Breast Cancer
Ann Surg Oncol 20:1436-1443, 2013
256,081 women diagnosed with T1e2 N0e3 M0 breast cancer from 2000 to 2008. We evaluated therapeutic mastectomy rates by the year of diagnosis and performed a multivariable logistic regression analyses to determine predictors of mastectomy as the treatment choice.
Mahmood U, Hanlon AL, Koshy M, et al (Univ of Texas MD Anderson Cancer Ctr, Houston; Univ of Pennsylvania, Philadelphia; Univ of Chicago, IL; et al)
56
Background.dTo study national trends in the mastectomy rate for treatment of early stage breast cancer. Methods.dWe analyzed data from the Surveillance, Epidemiology, and End Results database, including
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 1 2014
I. A. Petersen, MD
References 1. Casabona F, Bogliolo S, Valenzano Menada M, Sala P, Villa G, Ferrero S. Feasibility of axillary reverse mapping during sentinel lymph node biopsy in breast cancer patients. Ann Surg Oncol. 2009;16:2459-2463. 2. Cheville AL, Brinkmann DH, Ward SB, et al. The addition of SPECT/CT lymphoscintigraphy to breast cancer radiation planning spares lymph nodes critical for arm drainage. Int J Radiat Oncol Biol Phys. 2013;85:971-977. 3. 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: 2550-2555. 4. Gobardhan PD, Wijsman JH, van Dalen T, et al. ARM: axillary reverse mapping - the need for selection of patients. Eur J Surg Oncol. 2012;38: 657-661.