Axillary Lymph Node Dissection Arm Research Articles

Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (OPBC-03/SAKK 23/16/IBCSG 57-18/ABCSG-53/GBG-101-TAXIS).

TPS611 Background: Axillary lymph node dissection (ALND) is standard of care for most patients with clinically node-positive breast cancer (cN+BC), either in the adjuvant setting or in case of residual nodal disease after neoadjuvant chemotherapy (NACT). At least one quarter of patients with breast cancer experience long term morbidity after ALND. The TAXIS trial was designed to investigate if axillary radiotherapy (ART) can replace ALND in patients with cN+ BC who underwent tailored axillary surgery (TAS), which is recognized as one of the most important uncertainties and controversies in axillary management of patients with breast cancer. Methods: To test the remaining indications for ALND in clinical practice, we designed the international, multicenter, phase-III, non-inferiority, randomized controlled TAXIS trial to be pragmatic (average PRECIS-2 score of 4.44). Accordingly, most study domains follow usual care conditions, including eligibility (following routine indications for ALND in clinical practice), surgical skills and techniques, and follow up. The radiation oncology protocol included detailed recommendations and an extensive quality assurance program, which was developed to address the limitations of prior landmark trials and increase acceptability among recruiters. The main objective of the trial is to demonstrate that treatment with TAS and ART is non-inferior to TAS and ALND in terms of disease-free survival (DFS) of patients with cN+ BC detected by imaging or palpation in the upfront surgery setting or in case of residual disease after NACT. Randomization at a 1:1 ratio is mainly performed intraoperatively to either use TAS followed by ALND and regional nodal irradiation excluding the dissected axilla as a target volume (arm A) or to use TAS followed by regional nodal irradiation including the full axilla (arm B). The sample size is based on the primary endpoint DFS. With a type I error of 5% and a power of 80%, 385 events will be needed to show non-inferiority of TAS and axillary RT in comparison to ALND with a non-inferiority hazard ratio of 1.289 (corresponding to a DFS at 5 years of 80% in the ALND arm and 75% in the TAS and axillary RT arm). The sample size was calculated to be 1500 patients (750 per arm). Enrolment started in July 2018 and will stop after reaching 1500 patients, which is expected to be completed by Q4/2025. With currently 51 active sites from Europe, Canada and Korea within the network of the Oncoplastic Breast Consortium (OPBC), >950 patients were randomized by January 2024. Another 14 sites in Europe, USA, and South America will join the trial in 2024. The interim analysis (after 20% of the required events) is expected for Q4/2024 and will be reviewed by the IDMC. The primary endpoint analysis is planned in Q4/2030. Clinical trial information: NCT03513614 .

Abstract PO4-20-05: An open label phase III randomized trial to evaluate the efficacy of Post-chemotherapy Axillary Conservation Surgery in breast cancer (PACS)

Abstract Background- Axillary lymph nodes (ALN) status is the most important prognostic factor in breast cancer. Traditionally, a complete axillary lymph node dissection (ALND) has been standard of care for those patients who have a positive node pre-chemotherapy. However, lately axillary conservation is paving its way in the post-chemotherapy setting as well to avoid significant morbidity of ALND. Most sentinel node biopsy studies have failed to achieve the desired false negative rate(FNR). (Boughey JC et al, JAMA. 2013 Oct; Kuehn T et al, Lancet Oncol. 2013; Boileau JF et al, J Clin Oncol. 2015 Jan).We previously reported a low FNR of low axillary sampling (LAS) in the post-chemotherapy setting. (Parmar et al, JCO-GO, 2021) We are conducting a phase III, randomised controlled trial of LAS versus complete ALND in post-chemotherapy negative (ypN0) axilla. Aims and objectives- The primary objective is to assess the non-inferiority of LAS in patients who are rendered ypN0 by pre-operative chemotherapy with disease-free survival as primary end point. The secondary objectives are comparing the morbidity of ALND (lymphedema, paraesthesia, and shoulder dysfunction) in the LAS and ALND arms, and to evaluate the impact on overall survival, local, regional, and distant recurrence free survival and quality of life. Trial design- This is a prospective, open label, randomised, phase III trial where histologically proven, non-metastatic, cT1-4,N0-2 breast cancer patients who are rendered ycN0 after pre-operative systemic chemotherapy are being accrued. Patients with prechemo N3 disease, inflammatory breast cancer, recurrent disease, pregnancy associated breast cancer are being excluded from the study. The chemotherapy regimens and surgical assessment is as per standard institutional protocols. After obtaining informed consent, patients undergo LAS during surgery and lymph nodes(LN) are sent for frozen section analysis. If any LN is found to be involved, a complete ALND is carried out. If the staging procedure is negative, then patients are randomised into 2 groups- observation v/s complete ALND. Stratification factors are T stage, N stage, Hormone receptor status, Her2 receptor status and number of chemotherapy cycles taken. Morbidity assessment is done with- Constans shoulder score, arm volumetry, paraesthesia assessment, and a QOL questionnaire- Self-reported Breast cancer Lymphedema Symptom Experience Index (BCLSEI). A baseline assessment pre-surgery is followed by 6 monthly morbidity assessments and regular oncologically relevant follow-up up to 5 years. A two-sided log-rank test with an overall sample size of 2316 with a 10% dropout rate (1158 in ALND and 1158 in LAS group) achieves 80% power at a 0.05 significance level to detect a hazard ratio of 1.16 (upper limit of non-inferiority) when the proportion surviving in the control group is 0.71. An interim analysis will be carried out at 25% events and conditional power will be calculated. If the conditional power is below 20%, then the study will be discontinued for futility. The study has been approved by Institutional Ethics Committee (CTRI/2022/07/044461) Expected Study and Results- We started accrual in February 2023 and have screened 63 and randomized 45 patients until now. Ours is a first large randomised prospective study in the post-chemotherapy axillary management setting which will help us understand the efficacy of axillary conservation surgery in patients who are node negative post neoadjuvant chemotherapy. In future, lesser morbid procedures than LAS like targeted axillary dissection can be tested in the same trial. However, LAS as a technique of axillary conservation suits resource constraints and high volume setting such as ours. Citation Format: Shalaka Joshi, Jessicka Shah, Pallavi Daphale, Rohini Hawaldar, Anuradha Daptardar, Ayushi Sahay, Tanuja Shet, Palak Popat, Tabassum Wadasadawala, Nita Nair, Vani Parmar, Bipin Bandre, Shabina Siddique, Vaibhav Vanmali, Sudeep Gupta, Rajendra Badwe. An open label phase III randomized trial to evaluate the efficacy of Post-chemotherapy Axillary Conservation Surgery in breast cancer (PACS) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-20-05.

Prospective Analysis of Simulated Pneumatic Tourniquet Use and Oedema Following Axillary Lymph Node Dissection.

Background: Tourniquet use during upper extremity surgery in patients with a history of axillary lymph node dissection (ALND) remains controversial due to the perceived but unproven risk of lymphoedema. We prospectively evaluated upper extremity swelling in patients with a history of unilateral ALND using a standardised tourniquet model. Methods: A tourniquet was applied to the upper arm bilaterally, with the unaffected side serving as an internal control. Each arm was subsequently held in an elevated position to reduce swelling. Hand volume was measured using an aqueous volumeter. Results: The patients' ALND arms experienced slightly greater increases in volume following tourniquet application compared to their healthy control arms. However, this amount of oedema was temporary and reversible, as both arms experienced spontaneous resolution of swelling with no significant difference in residual hand volume at the conclusion of the study. Conclusions: Tourniquet use may be safe in patients with a history of ALND. Further investigation is needed to verify this in a surgical setting. Level of Evidence: Level II (Therapeutic).

Abstract PD15-11: PD15-11 Axillary dissection to determine nodal burden to inform systemic therapy recommendations in patients with clinically node-positive breast cancer: Pre-planned substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101)

Abstract Introduction: Chemotherapy is recommended for patients with luminal breast cancer and more than three positive nodes. In addition, recent landmark trials raised the question if the exact number of positive nodes is required to indicate genomic testing. In the neoadjuvant setting, response-driven therapy is increasingly used and may be influenced by surgical staging of the axilla. The present study addressed the role of axillary lymph node dissection (ALND) as decision aid for systemic therapy in a contemporary cohort of patients with clinically node-positive breast cancer in the adjuvant and neoadjuvant setting. Methods: The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614). The first 500 patients with clinically node-positive breast cancer who were randomized after tailored axillary surgery (TAS) to undergo ALND or axillary radiotherapy (ART) without ALND in the context of extended regional irradiation were included from August 2018 to June 2022. Clinically node-positive breast cancer was defined by confirmed nodal disease at the time of initial diagnosis; in case of neoadjuvant therapy, the finding of residual nodal disease was mandatory for randomization. TAS consisted of removal of palpably suspicious findings and the sentinel nodes with the option of image guidance. In the ART arm, the total number of positive nodes was not known. We analyzed the impact of ALND on rate and type of systemic therapy. Results: A total of 500 patients with a median age of 57 years (IQR: 48-69 years) were included at 44 breast centers from six European countries. Subtype was hormone receptor (HR) positive (+) and human epidermal growth factor receptor 2 (HER2) negative (-) in 393 (80.0%), HR+/HER2+ in 52 (10.6%), HR-/HER2+ in 5 (1.0%) and HR-/HER2- in 34 (6.9%) patients. Of 343 patients (68.6%) who were treated in the adjuvant setting, 297 had HR+/HER2- disease. Of these 297 patients, 145 (48.8%) underwent ART without ALND and 152 (51.2%) underwent ALND after TAS. In the ART arm, the median number of lymph nodes removed was five (IQR 4-8), three (IQR 1-4) of which were positive and in the ALND arm, the number was 19 (IQR 14-26), four (IQR 2-9) of which were positive (p < 0.001). The use of ALND had no significant impact on the rate of patients with HR+/HER2- disease undergoing adjuvant chemotherapy (51.0% in the ART and 57.9% in the ALND arm, p=0.2), and there were no significant differences in type of systemic therapy with the exception of tamoxifen, which was 18.4% with ALND versus 9.0% without (p=0.018). A total of 143 patients (28.6%) underwent neoadjuvant chemotherapy, 13 had neoadjuvant antihormonal treatment and one had neoadjuvant double HER2-blockade without chemotherapy. Of the 143 patients who received neoadjuvant chemotherapy, 71 (49.7%) underwent ART without ALND and 72 (50.3%) underwent ALND. In the ART arm, the median number of lymph nodes removed was four (IQR 3-6), one (IQR 1-3) of which was positive and in the ALND arm, the number was 16 (IQR 12-19), two (IQR 1-5) of which were positive (p < 0.001). The use of ALND in patients after neoadjuvant treatment had no significant impact on the rate of adjuvant systemic therapy (71.8% in the ART and 65.3% in the ALND arm, p=0.4), with no significant differences in type of chemotherapy (e.g., capecitabine: 11.3% vs 12.5%, p=0.8; T-DM1: 11.3% vs. 11.1%, p>0.9) or antihormonal therapy (e.g., aromatase inhibitors: 49.3% vs. 41.7%, p=0.4; tamoxifen: 11.3% vs. 5.6%, p=0.2). Discussion: This study showed that although ALND significantly increased the number of positive nodes removed in the adjuvant and neoadjuvant setting, it had no relevant impact on rate and type of adjuvant systemic therapy. Citation Format: Walter P. Weber, Zoltan Matrai, Stefanie Hayoz, Christoph Tausch, Guido Henke, Daniel R. Zwahlen, Günther Gruber, Frank Zimmermann, Thomas Ruhstaller, Simone Muenst, Markus Ackerknecht, Sherko Küemmel, Vesna Bjelic-Radisic, Viktor Smanykó, Conny Vrieling, Rok Satler, Inna Meyer, Charles Becciolini, Susanne Bucher, Colin Simonson, Peter M. Fehr, Natalie Gabriel, Robert Maráz, Dimitri Sarlos, Konstantin J. Dedes, Cornelia Leo, Gilles Berclaz, Hisham Fansa, Christopher Hager, Klaus Reisenberger, Ákos Sávolt, Christian F. Singer, Roland Reitsamer, Jelena Winkler, Giang Thanh Lam Lam, Mathias K. Fehr, Tatiana Naydina, Magdalena Kohlik, Karine Clerc, Valerijus Ostapenko, Florian Fitzal, Martin Heidinger, Nadia Maggi, Alexandra Schulz, Pagona Markellou, Loïc Lelièvre, Daniel Egle, Jörg Heil, Michael Knauer, Christian Kurzeder. PD15-11 Axillary dissection to determine nodal burden to inform systemic therapy recommendations in patients with clinically node-positive breast cancer: Pre-planned substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-11.

Preservation of Axillary Lymph Nodes Compared with Complete Dissection in T1-2 Breast Cancer Patients Presenting One or Two Metastatic Sentinel Lymph Nodes: The SINODAR-ONE Multicenter Randomized Clinical Trial.

The SINODAR-ONE trial is a prospective noninferiority multicenter randomized study aimed at assessing the role of axillary lymph node dissection (ALND) in patients undergoing either breast-conserving surgery or mastectomy for T1-2 breast cancer (BC) and presenting one or two macrometastatic sentinel lymph nodes (SLNs). The endpoints were to evaluate whether SLN biopsy (SLNB) only was associated with worsening of the prognosis compared with ALND in terms of overall survival (OS) and relapse. Patients were randomly assigned (1:1 ratio) to either removal of ≥ 10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). The trial started in April 2015 and ceased in April 2020, involving 889 patients. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB-only arm, respectively (p = 0.936). The 3-year survival and relapse rates of T1-2 BC patients with one or two macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND.

Axillary lymph node dissection vs. sentinel node biopsy for early-stage clinically node-negative breast cancer: a systematic review and meta-analysis.

ΟBJECTIVE: This study aimed at comparing survival outcomes between systematic axillary lymph node dissection (ALND) vs sentinel lymph node and axillary lymph node dissection only if sentinel positive (SLN ± ALND) in early-stage, clinically node-negative breast cancer patients. ΜETHODS: A systematic review and meta-analysis adhered to PRISMA guidelines was performed. Included studies were prospective randomized controlled trials (RCTs) comparing survival outcomes of ALND vs. SLN ± ALND in early-stage, node-negative breast cancer patients. Patients enrolled were only those with tumor size lower than 4cm, clinically negative nodes and treated with breast-conservative surgery. Primary endpoints were locoregional recurrence, overall death and cancer-related death. RESULTS: There were four studies included in the analysis, enrolling overall 2982 patients, of which 1494 in ALND arm and 1488 in the SLN ± ALND arm. No statistically significant difference was observed in locoregional recurrence, breast cancer-related death and overall death. Locoregional recurrence was observed in 2.8% (ALND) vs. 4.1% (SLND ± ALND), (RR 0.69, 95% CI 0.20-2.30). Overall death rate was 7.0% vs. 6.8% respectively, (RR 1.00, 95% CI 0.73-1.39, I2 = 28.7%). Breast cancer-related death was 3.6% vs. 3.5%, respectively (SLN ± ALND), (RR 1.11, 95% CI 0.70-1.78, I2 = 0%). No statistically significant difference was observed in any of secondary study outcomes. CONCLUSIONS: Systematic axillary axillary lymph node dissection provides no survival benefit compared with sentinel lymph node dissection for early-stage clinically node-negative breast cancer patients.

Axillary lymph node and non-sentinel lymph node metastasis among the ACOSOG Z0011 eligible breast cancer patients with invasive ductal, invasive lobular, or other histological special types: a multi-institutional retrospective analysis.

Given the histological special types (HST) of breast carcinoma accounted for minority of the Z0011 study population, this study aimed to assess the rates of axillary lymph node (ALN) involvement and non-sentinel lymph node (SLN) metastasis in patients with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), or other HST. Patients with cT1-2N0M0 breast cancer treated between 2009 and 2018 were retrospectively included from a multi-institutional database. Rates of nodal involvement were analyzed among different histological subgroups. The impact of ALN dissection (ALND) on adjuvant treatment decisions and prognosis were also analyzed among patients with 1-2 + SLNs. A total of 8294 patients were included: 6854 (82.6%), 257 (3.1%), and 1183 (14.3%) patients with IDC, ILC, and other HST, respectively. IDC patients had a significantly higher rate of ALN metastasis compared with ILC or other HST (31.9% vs. 22.6% vs. 16.4%, P < 0.001). However, in patients with 1-2 + SLNs, rates of non-SLN metastasis were similar among three groups (IDC: n = 182, 28.6% vs. ILC: n = 5, 31.2% vs. other HST: n = 29, 34.9%, P = 0.481). For patients with 1-2 + SLNs, rates of adjuvant chemotherapy and the estimated 3-year recurrence-free survival were similar between the SLN biopsy and ALND arms, regardless of the histological types. Among patients with 1-2 + SLNs, ILC or other HST had similar rates of non-SLN metastasis compared with IDC. Omission of ALND may not influence adjuvant chemotherapy usage or disease outcome regardless of histological types.

Abstract OT3-01-02: Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes: A multicenter randomized clinical trial. Sinodar One Study

Abstract Introduction Sentinel lymph node (SLN) staging is currently used to avoid complete axillary lymph node dissection (ALND) in breast cancer (BC) patients with negative SLNs without jeopardizing survival or regional control. International guidelines keep recommending ALND in the presence of positive (+) SLNs. However SLN is the only site of axillary metastasis (MTS) in many cases (60%). Retrospective studies have also shown a low risk of locoregional relapse in patients with SLNs+ not receiving ALND.This latter finding was recently confirmed in a randomized trial comparing SLN biopsy (SLNB) alone with SLNB followed by ALND in patients with 1-2 SLNs+. However the observation of both similar relapse rate and survival in the 2 arms and the conclusion of a non-inferiority of SLNB compared to ALND require cautiousness because of some study limitations: premature enrollment cessation due to death rate lower than expected, short follow-up (6 years), small tumor size (≤2cm in 70% of cases), frequent presence of only microMTS in SLN (40%), prevalent use of “whole breast” adjuvant radiotherapy (&amp;gt;90%) which irradiates the breast but also the I° axillary level, thereby contributing to the low rate of regional relapse in the SLNB arm due to lymph node sterilization. Consequently further randomized trials with more precise selection criteria based on homogeneous clinico-pathological features and with longer follow-up are needed to confirm that performing only SLNB does not affect survival or relapse risk in patients with 1-2 SLNs+. Materials and Methods Primary and secondary aims of the present 2-arm randomized trial are to assess whether ALND omission in BC patients with 1-2 SLNs+ is associated with worse survival and/or increased rate of regional/distant relapse, respectively, thus evaluating whether SLNB is or is not inferior to ALND. Patients receive either conservative surgery or mastectomy and radiotherapy. They all undergo intraoperative SLNB and SLN evaluation, and are randomly assigned to either further dissection of level I-II axillary lymph nodes (standard ALND arm) or absence of any axillary surgery (experimental SLNB arm). According to International Guidelines post-surgery treatments. Eligibility criteria are: age 40-75 years; primary invasive T1-T2 tumor; axillary nodes clinically N0; no more than 2 SLNs presenting macroMTS at intraoperative or definitive histological evaluation; no distant MTS; no neoadjuvant therapy; no previous invasive BC, signed informed consent. Exclusion criteria are: in situ, inflammatory, contralateral BC; presence of only microMTS in the SLN+; pregnancy or breast feeding; comorbidity impeding adjuvant therapy. Follow-up controls foresee: clinical examination every 6 months for 5 years and yearly thereafter; annual mammography and breast echography; annual axillary echography for patients in the SLNB arm; additional laboratory and instrumental surveys in case of suspected onset of distant MTS. The primary endpoint is overall survival (OS). Secondary endpoints are disease-free survival (DFS) referring to distant MTS and to locoregional (ipsilateral breast or axillary, internal mammary or sopraclaveolar lymph nodes) disease recurrence. All analyses are performed both on all patients according to the Intention-To-Treat principle and excluding those patients who did not receive the axillary treatment randomly assigned. Citation Format: Corrado Tinterri, Emilia Marrazzo, Federico Frusone, Wolfgang Gatzemeier, Erika Barbieri, Andrea Sagona, Alberto Bottini, Valentina Errico, Alberto Testori, Giuseppe Canavese. Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes: A multicenter randomized clinical trial. Sinodar One Study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-01-02.

Locoregional Recurrence After Sentinel Lymph Node Dissection With or Without Axillary Dissection in Patients With Sentinel Lymph Node Metastases: Long-term Follow-up From the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomized Trial.

The early results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated no difference in locoregional recurrence for patients with positive sentinel lymph nodes (SLNs) randomized either to axillary lymph node dissection (ALND) or sentinel lymph node dissection (SLND) alone. We now report long-term locoregional recurrence results. ACOSOG Z0011 prospectively examined overall survival of patients with SLN metastases undergoing breast-conserving therapy randomized to undergo ALND after SLND or no further axillary specific treatment. Locoregional recurrence was prospectively evaluated and compared between the groups. Four hundred forty-six patients were randomized to SLND alone and 445 to SLND and ALND. Both groups were similar with respect to age, Bloom-Richardson score, Estrogen Receptor status, adjuvant systemic therapy, histology, and tumor size. Patients randomized to ALND had a median of 17 axillary nodes removed compared with a median of only 2 SLNs removed with SLND alone (P < 0.001). ALND, as expected, also removed more positive lymph nodes (P < 0.001). At a median follow-up of 9.25 years, there was no statistically significant difference in local recurrence-free survival (P = 0.13). The cumulative incidence of nodal recurrences at 10 years was 0.5% in the ALND arm and 1.5% in the SLND alone arm (P = 0.28). Ten-year cumulative locoregional recurrence was 6.2% with ALND and 5.3% with SLND alone (P = 0.36). Despite the potential for residual axillary disease after SLND, SLND without ALND offers excellent regional control for selected patients with early metastatic breast cancer treated with breast-conserving therapy and adjuvant systemic therapy.

Sentinel Lymph Node Biopsy Versus Axillary Dissection in Node-Negative Early-Stage Breast Cancer: 15-Year Follow-Up Update of a Randomized Clinical Trial.

Sentinel lymph node biopsy (SLNB) allows for staging of the axillary node status in early-stage breast cancer (BC) patients and avoiding complete axillary lymph node dissection (ALND) when the sentinel lymph node (SLN) is proven to be free of disease. In a previous randomized trial we compared SLNB followed by ALND (ALND arm) with SLNB followed by ALND only if the SLN presented metastasis (SLNB arm). At a mid-term of≈6years median follow-up, the two strategies appeared to ensure similar survival and locoregional control. We have revised these previous findings and update the results following a 15-year observation period. Patients were randomly assigned to either the ALND or SLNB arm. The main endpoints were event-free survival (EFS), overall survival (OS), and axillary disease recurrence. EFS and OS were assessed using Kaplan-Meier analysis and the log-rank test. The ALND and SLNB arms included 115 and 110 patients, respectively. At 14.3years median follow-up, 39 primary BC-related recurrences occurred, 22 (19%) of which occurred in the ALND arm and 17 (16%) occurred in the SLNB arm (p=0.519). No axillary relapse developed in the SLNB arm, while two were observed in the ALND arm. OS (82.0 vs. 78.8%) and EFS (72.8 vs. 72.9%) were not statistically different between the ALND and SLNB arms (p=0.502 and 0.953, respectively). SLNB is a safe and efficacious component of the surgical treatment of early-stage BC patients. In the long-term, SLNB is equivalent to ALND in terms of locoregional nodal disease control and survival in this subset of patients.

Is sentinel lymph node biopsy enough for axillary macrometastasis?

includes patients with both micro and macrometastasis in sentinel lymph node(s). Early stage breast cancer patients with clinical N0 disease and one or two positive sentinel lymph node(s) are randomized to axillary lymph node dissection (ALND) vs. sentinel lymph node dissection (SLND) alone. At a median follow-up of 6.3 years, both 5-year overall survival (91.8% vs. 92.5%; ALND vs. SLND) and 5-year diseasefree survival (82.2% vs. 83.9%; ALND vs. SLND) are not significantly different between the arms (1, 2). Arguably, Z0011 study is one of the most important practice changing or at least practice questioning randomized study in recent years. The second trial is the International Breast Cancer Study Group (IBCSG) 23-01 study, which has the same patient population of Z0011 but with only one or 2 sentinel micrometastatic lymph node(s) and also the same randomization. In IBCSG 23-01 trial, the 5-year disease-free survival is also not significantly different between the groups (84.4% vs. 87.8%; ALND vs. SLND) (3). IBCSG 23-01 trial not only further strengthens the results of the Z0011 for the omittance of axillary dissection in patients with sentinel micrometastatic lymph node breast cancer but also shows that the quality of life (QOL) of patients could be improved with sentinel biopsy alone in terms of sensory motor neuropathy and lymphedema (3, 4). In the consensus report of Saint Gallen 2013, the policy of avoiding full axillary clearance after one or two positive sentinel nodes is endorsed in situations of conservative surgery and radiotherapy (73%, YES; 21%, NO), including several opinions that the inclusion criteria of the available trial results should be considered (5). Although the Z0011 trial provokes us to omit axillary dissection in patients with cT1-2cN0 disease finally staged at pT1-2pN1(sn), it creates more problems than it solves in terms of radiotherapy fields (1). The radiotherapy directed to axillary basins (i.e., third field nodal radiotherapy) is not allowed in the protocol of the Z0011 trial. However, the details of radiotherapy fields could not be clearly understood from the original report (1). Many radiation oncologists try to irradiate at least some part of the axillary level 1-2 (i.e., high-tangential fields) and even think of using third field (i.e., supraclavicular level 3), particularly for patients with no reasonable systemic treatment option (i.e., triple negative case). Recently, the detail of radiotherapy fields at least for some part of the patients in the Z0011 trial is presented at the San Antonio Breast Cancer Symposium 2013 (6). Detailed radiotherapy records were received for 228 patients only: 104/389 (26.7%) ALND vs. 124/404 (30.7%) SLND. Sixty-one of 104 (59%) patients in ALND arm also received some form of lymphatic radiotherapy [supraclavicular, n=22 (21%), posterior axillary boost n=6 (6%), and high tangents n=33 (32%)]. In the SLND arm, some form of lymphatic radiotherapy was also used for 73 of 124 (59%) patients [supraclavicular n=21 (17%), posterior axillary boost n=12 (10%), and high tangents n=40 (32%)] (6). Although the data of the central radiotherapy review of the entire Z0011 population could not be available currently, approximately 60% of the patients have received some form of lymphatic radiotherapy and 18.9% of them have major protocol violation (i.e., third field nodal radiotherapy is not allowed in the protocol). Thus, regional radiotherapy may contribute to the results that have been obtained from both arms of the Z0011 trial.

Radiation field design in the ACOSOG Z0011 (Alliance) Trial.

ACOSOG Z0011 established that axillary lymph node dissection (ALND) is unnecessary in patients with breast cancer with one to two positive sentinel lymph nodes (SLNs) who undergo lumpectomy, radiotherapy (RT), and systemic therapy. We sought to ascertain RT coverage of the regional nodes in that trial. We evaluated case report forms completed 18 months after enrollment. From 2012 to 2013, we collected all available detailed RT records for central review. Among 605 patients with completed case report forms, 89% received whole-breast RT. Of these, 89 (15%) were recorded as also receiving treatment to the supraclavicular region. Detailed RT records were obtained for 228 patients, of whom 185 (81.1%) received tangent-only treatment. Among 142 with sufficient records to evaluate tangent height, high tangents (cranial tangent border ≤ 2 cm from humeral head) were used in 50% of patients (33 of 66) randomly assigned to ALND and 52.6% (40 of 76) randomly assigned to SLND. Of the 228 patients with records reviewed, 43 (18.9%) received directed regional nodal RT using ≥ three fields: 22 in the ALND arm and 21 in the SLND arm. Those receiving directed nodal RT had greater nodal involvement (P < .001) than those who did not. Overall, there was no significant difference between treatment arms in the use of protocol-prohibited nodal fields. Most patients treated in Z0011 received tangential RT alone, and some received no RT at all. Some patients received directed nodal irradiation via a third field. Further research is necessary to determine the optimal RT approach in patients with low-volume axillary disease treated with SLND alone.

Abstract P5-14-19: Radiation field design on the ACOSOG Z0011 trial

Abstract Purpose/Objective: The landmark ACOSOG Z0011 trial established that axillary lymph node dissection (ALND) is unnecessary in breast cancer patients with one or two positive sentinel lymph nodes (SLN) who undergo lumpectomy, radiation therapy (RT) and systemic therapy. At a median follow-up of 6.3 years there were no differences in overall survival or local-regional recurrences between patients receiving ALND or SLN biopsy alone. The protocol required whole breast RT using standard tangential fields, but the extent of RT coverage of the regional nodes in these patients has not previously been described. We sought to ascertain this information. Methods: The RT data on the ACOSOG Z0011 trial was collected from case report forms completed by enrolling providers 18 months after enrollment. The response options on the forms included breast, supraclavicular, &amp; other. We reviewed these data and, in 2011-2013, we attempted to identify and contact all treating radiation oncology practices to request detailed radiation treatment records for central review. RT data was sent to the Quality Assurance Review Center (QARC) and reviewed by two independent radiation oncologists, blinded regarding the arm to which the patients were randomized. Results: Of the 891 patients enrolled on Z0011, 35 withdrew consent prior to surgery, leaving 856 who were analyzed in the primary report on trial outcomes.1 Among the 605 of these patients with a completed adjuvant radiation therapy form, 89% were noted to receive whole breast RT. Of these, 89 patients (15%) were recorded as also receiving treatment to the supraclavicular region. Detailed RT records were received on 228 patients: 104/389 (26.7%) and 124/404 (30.7%) on the ALND and SLND arms, respectively. Of the 228 patients, 185 patients (81.1%) received tangent-only treatment. Among these 185 patients, there was sufficient data to evaluate tangent field height in 142 (76.8%). High tangent RT fields (with cranial tangent border within 2 cm of the humeral head) were used in 52.6% (40/76) patients randomized to the ALND arm and 50% (33/66) patients randomized to the SLND arm. Of the 228 patients with records reviewed, 43 (18.9%) received directed regional nodal RT using ≥3 fields: 22 in the ALND and 21 in the SLND arm. Those receiving directed nodal RT tended to have greater nodal involvement (p&amp;lt;0.001). Conclusions: Most patients treated on the Z0011 trial received tangential field RT alone, and some received no radiotherapy at all. Some patients received directed nodal irradiation via a third field. In a subgroup for whom detailed RT records were available, the highest rates of directed nodal irradiation were among those with multiple nodes involved. As survival rates and local-regional recurrences were similar in the study arms, no conclusions can be drawn from this analysis on whether this additional radiation treatment was necessary or beneficial. 1JAMA 2011; 305 (6): 569-575. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-19.

Defining a threshold for intervention in breast cancer-related lymphedema: what level of arm volume increase predicts progression?

The purpose of this study is to evaluate arm volume measurements and clinico-pathologic characteristics of breast cancer patients to define a threshold for intervention in breast cancer-related lymphedema. We prospectively performed arm volume measurements on breast cancer patients using a Perometer. Arm measurements were performed pre- and post-operatively, and change in arm volume was quantified using a relative volume change (RVC) equation. Patient and treatment risk factors were evaluated. Cox proportional hazards models with time-dependent covariates for RVC were used to evaluate whether RVC elevations of ≥3 to <5% or ≥5 to <10% occurring ≤3months or >3months after surgery were associated with progression to ≥10% RVC. 1,173 patients met eligibility criteria with a median of 27months post-operative follow-up. The cumulative incidence of ≥10% RVC at 24months was 5.26% (95% CI 4.01-6.88%). By multivariable analysis, a measurement of ≥5 to <10% RVC occurring >3months after surgery was significantly associated with an increased risk of progression to ≥10% RVC (HR 2.97, p<0.0001), but a measurement of ≥3 to <5% RVC during the same time period was not statistically significantly associated (HR 1.55, p=0.10). Other significant risk factors included a measurement ≤3months after surgery with RVC of ≥3 to <5% (p=0.007), ≥5 to <10% (p<0.0001), or ≥10% (p=0.023), axillary lymph node dissection (ALND) (p<0.0001), and higher BMI at diagnosis (p=0.0028). Type of breast surgery, age, number of positive or number of lymph nodes removed, nodal radiation, chemotherapy, and hormonal therapy were not significant (p>0.05). Breast cancer patients who experience a relative arm volume increase of ≥3 to <5% occurring >3months after surgery do not have a statistically significant increase in risk of progression to ≥10%, a common lymphedema criterion. Our data support utilization of a ≥5 to <10% threshold for close monitoring or intervention, warranting further assessment. Additional risk factors for progression to ≥10% include ALND, higher BMI, and post-operative arm volume elevation.

Does the Result of Completion Axillary Lymph Node Dissection Influence the Recommendation for Adjuvant Treatment in Sentinel Lymph Node–Positive Patients?

ObjectiveThe Hungarian National Institute of Oncology has just closed a single-center randomized clinical study. The Optimal Treatment of the Axilla–Surgery or Radiotherapy (OTOASOR) trial compares completion axillary lymph node dissection (cALND) with regional nodal irradiation (RNI) in patients with sentinel lymph node-positive (SLN+) primary invasive breast cancer. In the investigational treatment arm, patients received 50 Gy RNI instead of cALND. In these patients we had information only about the sentinel lymph node (SLN) status, but the further axillary nodal involvement remained unknown. The aim of this study was to investigate whether the result of cALND influenced the recommendation for adjuvant treatment in patients with SLN+ breast cancer. Patients and MethodsPatients with SLN+ primary breast cancer were randomized for cALND (arm A, standard treatment) or RNI (arm B, investigational treatment). Adjuvant systemic treatments were given according to the standard institutional protocol, and patients were followed according to the actual institutional guidelines. ResultsBetween August 2002 and June 2009, 474 SLN+ patients were randomized to cALND (arm A, standard treatment = 244 patients) or RNI (arm B, investigational treatment = 230 patients). The 2 arms were well balanced according to the majority of main prognostic factors. However, more patients were premenopausal (34% vs. 27%; P = .095) and had pT2-3 tumors (57% vs. 40%; P = .003) in the completion axillary lymph node dissection (ALND) arm. On the other hand, there were more patients with known human epidermal growth factor receptor type 2 positive tumor (12% vs. 17%, P = .066) in the RNI arm. In the ALND and RNI arms, 78% (190/244) and 69% (159/230), respectively, received chemotherapy (P = .020). Endocrine therapy was administered in 87% (213/244) of the patients in the ALND arm and 89% (204/230) of the patients in the RNI arm (P = .372). Six patients (2.5%) on arm A and 13 patients (5.7%) on arm B received adjuvant trastuzumab treatment (P = not significant). Subgroup analyses explored that more frequent administration of adjuvant chemotherapy in arm A was associated with the higher percentage of premenopausal patients and patients with larger (pT2-3) tumors. ConclusionsThe result of cALND after positive SLN biopsy seems to have no major impact on the administration of adjuvant systemic therapy.

Applicability of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial results in invasive lobular carcinoma.

1103 Background: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that, for patients with clinical T1-T2, N0 breast cancer and one or two positive sentinel lymph nodes undergoing breast conserving therapy, there was no difference in local-regional recurrence (LRR), disease-free survival or overall survival (OS) between patients who underwent sentinel lymph node dissection (SLND) alone or completion axillary lymph node dissection (ALND). However, there were a limited number of invasive lobular carcinoma (ILC) participants (7%) in the study. In addition, it is known that ILC has a different pattern of metastases, frequently presenting as small foci requiring immunohistochemistry for detection. Together, these considerations raise concern regarding the applicability of the ACOSOG Z0011 data to patients with ILC. Methods: Patients with ILC who met the ACOSOG Z0011 eligibility criteria were identified from the Surveillance, Epidemiology, and End Results database (1998-2009). Patients were evaluated based on the extent of axillary surgery: SLND alone or ALND. Clinicaloutcomes of the two groups were compared. Results: At a median follow-up of 71 months, there were no LRRs in the SLND arm, and only 4 (0.45%) in the ALND arm. There were no differences in OS or disease-specific survival between the two groups. Conclusions: Omission of completion ALND is appropriate in patients with ILC who fulfill the ACOSOG Z0011 eligibility criteria.

Does the Rapid Acceptance of ACOSOG Z0011 Compromise Selection of Systemic Therapy?

The acceptance of sentinel lymph node (SLN) biopsy as standard care in cN0 breast cancer is one of the great success stories in contemporary surgical oncology and is supported by the results of at least 69 observational studies, 7 randomized trials, and extensive literature covering all aspects of the procedure. The logical next question in the evolution of axillary staging is to ask whether all SLNpositive patients require axillary lymph node dissection (ALND), and it is clear that for many American surgeons they do not. In a retrospective study from the National Cancer Data Base, Bilimoria et al. report on 97,314 SLNpositive patients treated nationwide between 1998 and 2006. They show 23 % of patients with SLN macrometastases ([2 mm, pN1) and 55 % with SLN micrometastases (0.2–2 mm, pN1mi) did not have ALND, yet for both pN1 and pN1mi SLN disease, axillary local recurrence and 5-year relative survival were the same with or without ALND. These suggestive results are of course subject to selection bias, but are confirmed by ACOSOG Z0011, a unique and visionary prospective trial that randomized 813 SLNpositive patients with clinical stage T1-2N0 breast cancer to ALND vs no further surgery. All patients were SLNpositive by routine H&E (not immunohistochemical) staining, and all had breast conservation including wholebreast RT. Patients with 3 or more positive SLN (or with matted nodes) were excluded, and formal axillary RT was not allowed. Additional positive nodes were found in 27 % of the patients who had ALND, but at 6 years’ follow-up there were no differences between the ALND and noALND arms in local (3.6 % vs 1.9 %), regional (0.5 % vs 0.9 %), or overall locoregional recurrence (4.1 % vs 2.8 %), nor were there any differences in disease-free or overall survival. Over the last 2 years many institutions and surgeons in the United States (and to a lesser extent in Europe and worldwide) have found the results of Z0011 to be persuasive and practice-changing, incorporating into their treatment guidelines a policy of ‘‘no-ALND’’ for SLN-positive patients who meet the Z0011 selection criteria. In this issue of the Annals, Montemurro and colleagues ask whether the growing acceptance of Z0011 may have been premature. Among 321 of their own SLN-positive breast cancer patients who matched the Z0011 selection criteria, all of whom had ALND, they ask how often the results of ALND were sufficient to change the systemic therapy. In their study design, 2 medical oncologists retrospectively reviewed each patient’s chart twice, first making a recommendation for systemic therapy based on SLN status alone, and then incorporating the results of the ALND. They found that the information gained from the ALND changed the recommended treatment in 16 % of patients, most of them ER-positive/her2-negative (luminal A and B) and most in the direction of ‘‘ACT’’ (doxorubicin, cyclophosphamide, and paclitaxel) chemotherapy. They conclude by suggesting that to avoid undertreatment ALND may be appropriate for some, if not all, SLNpositive patients meeting the Z0011 criteria. Their argument deserves serious consideration, but I do not share their concerns, for the following reasons. First, the subtext of their study is the hypothesis that there are node-positive patients who do not require chemotherapy. This is expressed obliquely in the 2011 St. Gallen Consensus document: ‘‘the Panel did not believe that node positivity per se was an indication for use of chemotherapy, though a strong majority would use it if more than 3 lymph nodes were involved.’’ This fits with the authors’ observation that ALND changed therapy primarily by finding additional positive nodes in those SLNSociety of Surgical Oncology 2012

Abstract PD06-09: Sentinel Node Biopsy Versus Axillary Lymph Node Dissection in Early-Stage Breast Cancer: A Meta-Analysis of Randomized Controlled Trials

Abstract Background: Lymphatic mapping with sentinel node biopsy (SNB) has become a widely used technology for reducing morbidity associated with breast cancer staging despite limited data from randomized controlled trials (RCTs). A previous review of cohort studies conducted for ASCO guidelines prior to results from RCTs found considerable variation in SNB staging accuracy. (Kim et al, Cancer 2005; Lyman GH et al J Clin Oncol 2005). Early results from several RCTs of SNB have now been reported. Methods: A systematic review of RCTs of SNB for breast cancer staging was conducted utilizing electronic databases. Study eligibility was limited to RCTs comparing SNB alone in SNB negative patients versus axillary lymph node dissection (ALND) with or without prior SNB. SNB staging accuracy was assessed in study arms where patients were randomized to immediate ALND. Data abstraction was conducted by two independent reviewers. Rates of axillary, locoregional and all recurrence were evaluated along with all-cause and breast cancer-specific mortality. Heterogeneity was assessed by Cochran's Q-statistic and the Inconsistency Index (I2). Weighted summary measures of relative risk (RR) and absolute risk difference (ARD) with 95% CIs were estimated using the method of Mantel-Haenszel. Results: Seven eligible RCTs were identified of which six, involving 9,389 patients, reported either SNB performance and/or rates of recurrence and mortality. Eligibility in these studies was restricted to patients with clinically negative nodes with four limiting accrual to tumors &amp;lt;2-3 cm. Technical success of mapping was reported in five trials including 4,184 (97.1%) and 4,180 (96.8%) patients randomized to SNB versus SNB with immediate ALND, respectively. SNB was positive in 26.5% and 25.4% in those randomized to the SNB and SNB plus ALND arms, respectively. The false negative rate with SNB ranged from 5.5% to 22.9% with a summary estimate of 11.3% [7.5%-16.8%]. The median duration of follow-up across trials ranged from 12 to 95 months with an overall median of 65 months. The risk of axillary recurrence ranged from 0 - 0.8% in SNB patients and 0-0.9% in ALND patients, respectively with RR for axillary recurrence for SNB versus ALND patients of 1.59 [0.67-3.75; P=.292] and ARD of 0.2% [-0.01%-0.4%; P=.082]. The risk of locoregional recurrence ranged from 0.2%-4.6% in SNB patients and 0.8%-3.5% in ALND patients with RR of 1.13 [0.53-2.33; P=.776] and ARD of 0.3% [-1.0%-1.5%; P=.679]. Mortality from any cause has been reported in 222 and 196 patients in the SNB and ALND arms, respectively, with RR for mortality of 1.13 [0.94-1.36; P=.202] and ARD of 0.6% [-0.3%-1.6%; P=.201]. Breast cancer-specific mortality has been reported in 31 and 34 patients in the SNB and ALND arms, respectively, with a RR of 0.90 [0.56-1.45;P=.676] and ARD of 0.3% [-1.6%-1.0%; P=.676]. Conclusions: The overall false negative rate with SNB greater than 10% and limited follow-up continue to raise concerns. While no increase in risk of recurrence or mortality in low risk patients managed primarily with SNB is evident to date, continued observation in these studies will be important in addition to more specific data on the accuracy and safety of SNB in higher risk patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD06-09.

Role of Axillary Clearance After a Tumor-Positive Sentinel Node in the Administration of Adjuvant Therapy in Early Breast Cancer

PURPOSE The After Mapping of the Axilla: Radiotherapy or Surgery? (AMAROS) phase III study compares axillary lymph node dissection (ALND) and axillary radiation therapy (ART) in early breast cancer patients with tumor-positive sentinel nodes. In the ART arm, the extent of nodal involvement remains unknown, which could have implications on the administration of adjuvant therapy. In this preliminary analysis, we studied the influence of random assignment to ALND or ART on the choice for adjuvant treatment. PATIENTS AND METHODS In the first 2,000 patients enrolled in the AMAROS trial, we analyzed the administration of adjuvant systemic therapy. Multivariate analysis was used to assess variables affecting the administration of adjuvant chemotherapy. Adjuvant therapy was applied according to institutional guidelines. Results Of 2,000 patients, 566 patients had a positive sentinel node and were treated per random assignment. There was no significant difference in the administration of adjuvant systemic therapy. In the ALND and ART arms, 58% (175 of 300) and 61% (162 of 266) of the patients, respectively, received chemotherapy. Endocrine therapy was administered in 78% (235 of 300) of the patients in the ALND arm and in 76% (203 of 266) of the patients in the ART arm. Treatment arm was not a significant factor in the decision, and no interactions between treatment arm and other factors were observed. Multivariate analysis showed that age, tumor grade, multifocality, and size of the sentinel node metastasis significantly affected the administration of chemotherapy. Within the ALND arm, the extent of nodal involvement remained not significant in a sensitivity multivariate analysis. CONCLUSION Absence of knowledge regarding the extent of nodal involvement in the ART arm appears to have no major impact on the administration of adjuvant therapy.

Technical aspects of the sentinel node biopsy in the EORTC AMAROS sentinel node trial.

Abstract Abstract #1006 Background: The AMAROS trial is a phase III study comparing axillary lymph node dissection (ALND) with axillary radiation therapy (ART) in patients with proven axillary metastasis by sentinel node biopsy (SNB). The main objective of the trial is to prove equivalent locoregional control and reduced morbidity for ART. The aim of this interim analysis was to analyze the technical aspects of the SNB.&amp;#x2028; Methods: The first 2000 patients with operable unifocal invasive breast cancer (5-30 mm) and clinically negative lymph nodes enrolled in the AMAROS trial between 2001 and 2005 were analyzed. The 26 participating institutions have been site visited as part of the surgical quality assurance. SNB is performed using preoperative lymphoscintigraphy, blue dye and a gamma-ray detection probe. Patients with a negative sentinel node were not subjected to ALND or ART.&amp;#x2028; Results: The SN identification rate was 97% (range per institute 89%- 99%), 33% (n=658) of the patients were SNB positive, 62% (n=1245) were SNB negative and 2%(n=32) had other outcomes (non-axillary, missing data). Median two sentinel nodes were removed in the SNB positive as well as the SNB negative group. In 17% (344) of the patients, non-blue and non radio-active nodes were removed during the sentinel node procedure, median 1 node. In 11 patients, these nodes were the only tumor positive nodes found. In the SNB positive group the incidence of macro-, micrometastasis and isolated tumor cells was 61% (389), 26% (164) and 13% (80), respectively. In the ALND arm, further nodal involvement was seen 47,5% , 21,4 % and 16,7%, respectively. There was no correlation between the size of metastasis and the tumor size, grade or histological subtype. Of the sentinel nodes 59% (1907/3259) were radioactive and blue, 33% (1087/3259) were only radioactive, 8 %(265/3259) were only blue. Non-visualization on lymphoscintigraphy was seen in 7.6%(152), in 78%(118) of these cases a sentinel node was found during surgery. At least one sentinel node was located in the axilla in 89%(1777), in the internal mammary chain in 5% (104) and infra/supraclavicular in 1%(15). The injection site was intra/peritumoral in 53% subcutane/intradermal over the tumor in 9% periareolair in 16%, a combination in 4%, missing data 17%. Sentinel nodes in the internal mammary chain were significantly correlated with a intratumoral injection technique.&amp;#x2028; Conclusions: These results indicate that with a 97% detection rate in this prospective international multicenter study using the combination of radioactive tracer and blue dye, the sentinel node procedure is highly effective. Differences in injection site affect the finding of non axillary sentinel nodes. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1006.