Axillary Recurrence Research Articles

267 Axillary Recurrence Following Negative Sentinel Lymph Node Biopsy for Symptomatic Invasive Breast Cancer: A Ten-Year Review

Abstract Aim Sentinel node biopsy (SNB) became established as the standard approach (versus axillary clearance) for axillary staging in the 2000s. This was based on studies showing reductions in short-term morbidity. Symptomatic cancers are biologically more aggressive than screen-detected cancers and are more susceptible to late loco-regional recurrence. Few studies have examined long-term axillary recurrence following SNBs in this subgroup. Method A retrospective case-note review was performed on 82 symptomatic breast cancer patients who had a negative SNB between 2009 and 2010. Clinicopathological data was collected on cancers, axillary nodal pathology, recurrence, and survival. Results Median age was 57 years (range 23–87). Mean tumour size was 20mm (range: 5–50). Fourteen cancers (17%) were ER negative, 11 (19.3%) HER2 positive and 30 (36.3%) were grade 3. Sixty-one (74%) patients had breast-conserving surgery and 21 patients (26%) underwent a mastectomy. After a median follow up of 11.8 years, 3 (3.7%) local, 1 (1.2%) axillary and 10 (12.2%) distant recurrences were seen. Twenty patients (25%) died. The median OS was 11.64 years (range: 1.20–12.47) and median DFS was 11.50 years (range: 1.14–12.47). Axillary recurrence rates were comparable to other studies that contained predominantly screening cancers (0.7–1.6%). Conclusion The risk of axillary recurrence and remains low at 10-year follow up after a negative SNB in symptomatic patients. This is comparable to that of follow up studies in mixed (screening and symptomatic) cohorts demonstrating equivalent long-term oncological safety in this biologically more aggressive cohort.

Comparing Early-Stage Breast Cancer Patients with Sentinel Lymph Node Metastasis with and without Completion Axillary Lymph Node Dissection: A Systematic Review and Meta-Analysis.

Currently, the standard method for staging and treatment of axillary lymph nodes for early-stage breast cancer is sentinel lymph node biopsy (SLNB), while axillary lymph node dissection (ALND) is used in cases with palpable axillary lymph nodes or positive SLNB cases. The aim of this review was to compare overall survival (OS), disease-free survival (DFS), and axillary recurrence in early-stage breast cancer patients underwent SLNB or SLNB and completion ALND. The databases of PubMed, Scopus, and Cochrane Library were searched using the key words of "breast cancer", "axillary lymph node dissection", and "sentinel lymph node dissection". In addition, other sources were searched for ongoing studies (i.e., clinicaltrials.gov). The clinical trials were evaluated based on the Jadad quality criteria, and cohort studies were evaluated according to the STROBE criteria. At the end of the search, the articles were screened independently by two reviewers to check their eligibility to be included in the study. Afterwards, the data were extracted independently by two researchers. After searching the databases, 169 papers were retrieved. However, after removing the duplicates and studying the titles and abstracts of these papers, only ten ones underwent further investigation. After reading full-text of each article, four studies were finalized. Following a manual search, 27 papers were entered into the study for the final evaluation, 11 of which were included in the meta-analysis based on the inclusion and exclusion criteria. The findings showed no significant differences in OS, DFS, and axillary recurrence in early-stage breast cancer patients underwent SLNB or SLNB and completion ALND. The findings did not confirm that ALND improved OS, DFS, and axillary recurrence in patients who were clinically node-negative and positive SLNB.

Sentinel node biopsy and regional recurrence following neoadjuvant chemotherapy in patients with isolated tumor cells: A rare event.

e12581 Background: Lack of consensus exists regarding the optimal surgical axillary management of breast cancer patients treated with neoadjuvant therapy followed by sentinel node biopsy (SNB) with only isolated tumor cells (ITCs) identified in the sentinel node (SN). Few studies with limited patients have addressed this. A prospectively maintained database was reviewed to identify residual nodal metastatic burden and outcomes for patients with SN ITCs. Methods: Operable breast cancer patients treated with neoadjuvant therapy followed by breast surgery with SNB were identified who had only ITCs in the SN. Patients were excluded who had recurrent breast cancer, metastatic disease at time of operation, or who had an operation performed at another institution. Residual burden of axillary metastatic disease in patients who underwent completion axillary dissection and locoregional recurrence were examined. All SNs were examined with both hematoxylin and eosin stains as well as well as immunohistochemical stains. Results: 875 patients underwent neoadjuvant therapy followed by breast surgery and SNB from July 2007 to November 2021. Seventeen patients (1.9%) had only ITCs in the SN. The mean patient age of these 17 patients was 55.6 years (range 31-83 years). The majority had invasive ductal carcinoma (n = 15, 88.2%). Fourteen patients (82.4%) had ER+ tumors, 11 (64.7%) PR+ tumors, 2 patients (11.7%) had HER2+, and 3 patients (17.6%) had triple negative cancers. All patients had clinical T1 to T3 tumors and clinical N0 (n = 11, 64.7%), N1 (n = 5, 29.4%), or N2 (n = 1, 5.9%) disease. Two patients had isolated tumor cells identified on frozen section. Both of these patients underwent axillary dissection during the index operation and had further nodal disease identified (1 patient with ITCs only and 1 patient with macrometastasis). Fourteen patients had SN tumor free frozen sections but ultimately had ITCs identified with H&E. Five of these patients underwent a completion axillary dissection. Three of the 5 patients (60%) had additional ITCs identified after completion ALND. Fourteen patients had nodal irradiation. The three patients who did not receive irradiation did not undergo ALND. All patients with ER+ tumors received adjuvant endocrine therapy, the 2 patients with HER2+ cancers received adjuvant targeted HER2 therapy, and 4 patients received adjuvant chemotherapy. At a mean follow-up of 21.8 months (range 2-63 months), no locoregional recurrences occurred in any patient. Conclusions: ITCs in the SN after neoadjuvant therapy is a rare finding and are unlikely to be associated with regional recurrence.

Diagnostic performance and survival outcome following sentinel lymph node biopsy in breast cancer patients from a tertiary cancer centre in India.

BackgroundSentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) for axillary staging in early node-negative breast cancer (BC) patients in developed countries. However, in resource-constrained developing countries, adoption of SLNB is slow due to logistic issues and lack of outcome data from non-screened BC cohort. Therefore, we aim to report diagnostic performance, surgical morbidity and survival outcome of SLNB in BC patients from a tertiary care cancer centre in India.Methodology1,521 consecutive early node-negative T1-3N0 BC patients having SLNB from 2011 to 2020 were included in the study. Data were retrieved from the institutional Redcap database and electronic medical records. Analysis was done using Stata14.ResultsSLNB was done by dual dye (methylene blue (MB) + radioisotope (RI)/indo cyanine green (ICG)) in 57.7%, MB only in 39.3%, and RI alone in 3% of patients. The identification rate (IR) and SLNB positivity rate were 96% and 27.7%, respectively. IR was highest (98%) with MB + ICG and lowest (94%) with MB alone SLNB. UltraSonoGraphy guided fine needle aspiration cytology of radiological suspicious nodes has significantly reduced the SLNB positivity rate from 34.6% to 26.4% (p < 0.01). One patient had skin necrosis, and 16 had persistent blue staining of the skin in the MB injection site. All were managed conservatively. The lymphedema rate was significantly higher (5.2%) in the ALND versus 0.5% in the SLNB alone patients (p < 0.05). In a median follow up of 27 months, the axillary recurrence rate was 0.04% (4/1,023), and false-negative rate was 0.9% in SLNB negative patients. There were 35 recurrences and 25 deaths in SLNB negative patients, with 10 years predicted disease-free survival of 81% (95% CI 66% to 89%) and overall survival of 79% (95% CI 59% to 90%).ConclusionsSLNB should be offered as an axillary staging procedure to all eligible BC patients from developing countries to avoid the morbidity associated with ALND. Fluorescent dye can be used as an alternative for RI in a resource-constrained setup.

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 recurrence following negative sentinel lymph node biopsy for symptomatic invasive breast cancer: A ten-year review

Aims: Sentinel node biopsy (SNB) became established as the standard approach (versus axillary clearance) for axillary staging in the 2000s. This was based on studies showing reductions in short-term morbidity. Symptomatic cancers are biologically more aggressive than screen-detected cancers and are more susceptible to late loco-regional recurrence. Few studies have examined long-term axillary recurrence following SNBs in this subgroup.

Higher risk tumor features are not associated with higher nodal stage in patients with estrogen receptor-positive, node-positive breast cancer.

Studies support omission of axillary lymph node dissection (ALND) for patients with sentinel node-positive disease, with ALND recommended for patients who present with clinically positive nodes. Here, we evaluate patient and tumor characteristics and pathologic nodal stage of patients with estrogen receptor-positive (ER +) breast cancer who undergo ALND to determine if differences exist based on nodal presentation. Retrospective chart review from 2010 to 2019 defined three groups of patients with ER + breast cancer who underwent ALND for positive nodes: SLN + (positive node identified at SLN biopsy), cNUS (abnormal preoperative US and biopsy), and cNpalp (palpable adenopathy). Patients who received neoadjuvant chemotherapy or presented with axillary recurrence were excluded. Of 191 patients, 94 were SLN + , 40 were cNUS, and 57 were cNpalp. Patients with SLN + compared with cNpalp were younger (56 vs 64years, p < 0.01), more often pre-menopausal (41% vs 14%, p < 0.01), and White (65% vs 39%, p = 0.01) with more tumors that were low-grade (36% vs 8%, p < 0.01). Rates of PR + (p = 0.16), levels of Ki67 expression (p = 0.07) and LVI (p = 0.06) did not differ significantly among groups. Of patients with SLN + disease, 64% had pN1 disease compared to 38% of cNUS (p = 0.1) and 40% of cNpalp (p = 0.01). On univariable analysis, tumor size (p = 0.01) and histology (p = 0.04) were significantly associated with pN1 disease, with size remaining an independent predictor on multivariable analysis (p = 0.02). Historically, higher risk features have been attributed to patients with clinically positive nodes precluding omission of ALND, but when restricting evaluation to patients with ER + breast cancer, only tumor size is associated with higher nodal stage.

A propensity score-matched analysis of breast-conserving surgery plus whole-breast irradiation versus mastectomy in breast cancer.

Recent observations regarding long-term outcomes among patients with early-stage breast cancer (BC) who underwent breast-conserving surgery (BCS) plus whole-breast irradiation (WBI) or mastectomy are from a small number of registry-based studies. Therefore, these findings may overestimate differences in survival between the two groups, compared with randomized controlled trials conducted in the 1980s. The aim of this study is to compare long-term outcomes and clinicopathologic characteristics between patients treated with BCS + WBI or mastectomy for BC. We performed a propensity score-matched analysis in a cohort of 9710 patients aged < 70years who underwent BCS + WBI or mastectomy without external radiotherapy for a first primary BC (pT1-2, N0-3a) at the European Institute of Oncology between 2000 and 2008. Patients were matched by propensity score. Median follow-up was 8.4years (interquartile range 6.5-10.2). The cumulative incidence of axillary lymph node recurrence at 10years was lower in the BCS + WBI group [2.4% (95% CI, 1.7-3.3%)] than in the mastectomy group [4.4% (95% CI, 3.5-5.5%)] (P = .0005), and the cumulative incidence of contralateral BC was higher in the BCS + WBI group [3.9% (95% CI, 2.8-5.1%)] than in the mastectomy group [2.5% (95% CI, 1.7-3.4%)] (P = .01). Among the 366 patients with HER2 subtype BC, BCS + WBI was associated with a fivefold higher risk [hazard ratio 4.97 (95% CI, 2.28-10.8)] of ipsilateral breast tumor recurrence (IBTR), compared with mastectomy (P < .0001); however, among patients with other BC subtypes, the rates of IBTR were not statistically significantly different. Patients with HER2 subtype BC (T1-2, N0-3) who underwent BCS + WBI had a statistically significantly higher risk of IBTR than patients who underwent mastectomy. Survival was not statistically significantly different between the groups.

Isotope-Only Localization for Sentinel Lymph Node Biopsy - Medium-Term Oncological Outcomes

AimsIsotope and blue dye dual localization in sentinel lymph node biopsy (SLNB) gives localization rates of over 98% and is the recommended technique. However blue dye risks a range of adverse reactions. Since 2010, for clinically node negative disease, we have only used blue dye if there is no clear isotope signal at surgery. MethodsElectronic records of patients who underwent isotope-only SLN localization between July 2010 and April 2012 were examined. Data were collected on localization and oncological outcomes. Results426 patients were included. Isotope-only localization rate was 97.4% (415/426). The median follow-up was 63.5 months (IQR: 60.7-70.9). Median age was 57 (IQR: 48-67). Median SLN yield was 2 (range: 1-5). Axillary recurrence rate was 1.4% with median time to recurrence of 39.3 months. In-breast recurrence, distant disease and contralateral breast cancer rates were 2.8%, 7%, and 1.9% respectively and 15 (3.5%) patients died of metastatic breast cancer. ConclusionIsotope-only SLNB has a comparable localization rate to dual isotope/blue dye SLNB and can spare the risk of blue dye adverse reactions. The low axillary recurrence rate, maintained to more than 5 years, confirms that isotope-only SLNB is a feasible and safe alternative to dual blue dye/isotope localization.

No axillary surgical treatment for lymph node-negative patients after ultra-sonography [NAUTILUS]: protocol of a prospective randomized clinical trial

BackgroundFollowing sentinel lymph node biopsy (SLNB), the axillary recurrence rate is very low although SLNB has a false-negative rate of 5–10%. In the ACOSOG Z0011 trial, non-sentinel positive-lymph nodes were found in more than 20% of the axillary dissection group; the SLNB only group did not have a higher axillary recurrence rate. These findings raised questions about the direct therapeutic effect of the SLNB. SLNB has post-surgical complications including lymphedema. Considering advances in imaging modalities and adjuvant therapies, the role of SLNB in early breast cancer needs to be re-evaluated.MethodsThe NAUTILUS trial is a prospective multicenter randomized controlled trial involving clinical stage T1–2 and N0 breast cancer patients receiving breast-conserving surgery. Axillary ultrasound is mandatory before surgery with predefined imaging criteria for inclusion. Ultrasound-guided core needle biopsy or needle aspiration of a suspicious node is allowed. Patients will be randomized (1:1) into the no-SLNB (test) and SLNB (control) groups. A total of 1734 patients are needed, considering a 5% non-inferiority margin, 5% significance level, 80% statistical power, and 10% dropout rate. All patients in the two groups will receive ipsilateral whole-breast radiation according to a predefined protocol. The primary endpoint of this trial is the 5-year invasive disease-free survival. The secondary endpoints are overall survival, distant metastasis-free survival, axillary recurrence rate, and quality of life of the patients.DiscussionThis trial will provide important evidence on the oncological safety of the omission of SLNB for early breast cancer patients undergoing breast-conserving surgery and receiving whole-breast radiation, especially when the axillary lymph node is not suspicious during preoperative axillary ultrasound.Trial registrationClinicalTrials.gov, NCT04303715. Registered on March 11, 2020.

Abstract OT1-04-02: The NAUTILUS trial (No Axillary sUrgical Treatment In clinically Lymph node negative patients after UltraSonography): A prospective multicenter randomized phase III trial (NCT04303715)

Abstract Background. Sentinel lymph node biopsy (SLNB) is currently the standard axillary staging procedure for clinically node-negative breast cancer. According to the ACOSOG Z0011 trial, axillary lymph node dissection (ALND) is now often omitted for clinically node-negative cT1-2 breast cancer patients undergoing breast-conserving surgery even if 1 or 2 metastatic lymph nodes (LN) are identified. It was shown that radiotherapy contributes to regional control of the axilla non-inferior to ALND even in the presence of metastatic LNs. Furthermore, LN metastasis has a limited role in planning adjuvant systemic therapy for hormone receptor-negative breast cancers, and also for hormone receptor-positive, HER2-negative breast cancer with increased use of genomic assays. SLNB is not without complications and omitting axillary staging operation could improve quality of life. Trial Design. In this multicenter, phase III randomized controlled trial including 9 study sites in South Korea, we plan to 1:1 randomize 1734 patients to either omit SLNB (Arm 1) or receive SLNB (Arm 2). Additional ALND can be performed according to the discretion of the surgeon according to the SLNB results. All patients must receive whole-breast irradiation ± tumor bed boost. The recommended upper margin of the radiation field is within 2cm of the humeral head. ClinicalTrials.gov identifier: NCT04303715. Eligibility. Inclusion criteria: women ≥19 years; cT1-2N0M0 unilateral invasive breast carcinoma; all molecular subtypes; clinically and radiologically tumor size ≤ 5cm; clinically- and ultrasonogram-negative axillary lymph nodes, or no tumor on core needle biopsy or fine needle aspiration cytology in case of suspicious lymph nodes; candidate for breast-conserving surgery with no restriction to radiotherapy and adequate systemic therapy. Exclusion criteria: history of any malignancy within 5 years (exception: thyroid cancer and well-treated skin cancer except melanoma); bilateral breast cancer; neoadjuvant chemotherapy; candidate for total mastectomy; male breast cancer. Specific Aims. Primary objective is to test the hypothesis that omitting SLNB for breast cancer is non-inferior to axillary staging operation in terms of 5-year disease-free survival. Secondary objectives are to compare overall survival, distant metastasis-free survival, locoregional recurrence, quality of life assessment, and DFS and axillary recurrence according to molecular subtypes. Statistical Methods. With an expected 5-year DFS of 86% for Arm 2, Arm 1(SLNB omission) will be assessed with a non-inferiority limit of 5% and hazard ratio of 1.4, power 80%, and significance level of 5%, where 224 events are required. The calculated sample size is 780 per study arm, resulting in a total of 1,734 patients assuming a 10% drop-out rate. Present Accrual and Target Accrual. The first patient was randomized on September 15, 2020. As of July 9, 2021, 480 patients have been randomized. Target accrual of 1734 patients is expected to be complete by April 2023, with the primary endpoint analysis expected in 2028. Citation Format: Han-Byoel Lee, Ji Gwang Jung, Jung Min Chang, Ji Hyun Chang, Woo Kyung Moon, Kyung Hwan Shin, Il Yong Chung, Seok Jin Nam, Eun-Kyu Kim, Seeyoun Lee, Seho Park, Woo Sung Lim, Yongsik Jung, Wonshik Han. The NAUTILUS trial (No Axillary sUrgical Treatment In clinically Lymph node negative patients after UltraSonography): A prospective multicenter randomized phase III trial (NCT04303715) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-04-02.

Abstract GS4-05: 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

Abstract Introduction: Sentinel lymph node (SLN) staging is currently used to avoid complete axillary lymph node dissection (ALND) in breast cancer (BC) patients. The SLN is the only site of axillary metastasis (MTS) in ≥60% of cases. Recently, a randomized controlled trial (Z0011) comparing SLN biopsy (SLNB) alone with SLNB followed by ALND in patients with 1-2 SLNs+ demonstrated no significant statistical difference in relapse and overall survival (OS) rates among the two different groups. However, this study had some limitations: 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%). Given these considerations, the SINODAR-ONE study started in April 2015. Objectives: The aims 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. Thus evaluating whether SLNB is or is not inferior to ALND. Primary endpoint is OS. Secondary endpoints are disease-free survival (DFS) referring to distant MTS and loco-regional recurrence. Methods: Patients received either mastectomy or conservative surgery plus radiotherapy. They all underwent SLNB and were randomly divided into two arms of treatment: standard (SLNB plus ALND) or experimental treatment (only SLNB). According to multidisciplinary evaluation, patients could undergo additional adjuvant radiotherapy, chemo- and/or hormonal therapy, or no further therapy. Eligibility criteria: age 40-75 years; primary invasive T1-T2 tumor; axillary nodes cN0; no more than 2 macro-metastatic SLNs; no distant MTS; no neo-adjuvant therapy; no previous invasive BC. Exclusion criteria: in situ, inflammatory, contralateral BC; micro-metastatic SLNs; pregnancy or breast feeding; comorbidity impeding adjuvant therapy. All analyses were 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. Statistical analysis: OS and DFS were calculated using the Kaplan-Meier Product Limit Estimator and differences between arms were assessed with the log-rank test. Results: The enrollment of patients ended in April 2020 with a total of 889 cases (443: standard arm; 446: experimental arm). In April 2021, we conducted a preliminary analysis on 889 patients. We found the two groups homogeneous for epidemiologic characteristics (age and menopausal status), tumor characteristics (tumor size, pTNM, immunohistochemistry, histology, grading, vascular and lymphatic invasion), and adjuvant therapies. The majority of patients (77.2%) received breast conserving surgery, while 22.8% of patients underwent mastectomy. A median of 2 SLNs were removed in both arms. Overall, only 3 micro-metastatic SNLs were found (1 in the standard arm and 2 in the experimental arm). Conclusion: In sum, OS rate is 99.1% and 99.3% in the standard and experimental arm, respectively; DFS rate is 96.8% and 95.9% in the standard and experimental arm, respectively. After a median follow-up of 36 months, there has been only one axillary recurrence in the experimental arm. Additionally, we found seven distant relapses in both arms; four and three deaths in the standard and experimental arm, respectively. Citation Format: Damiano Gentile, Wolfgang Gatzemeier, Erika Barbieri, Andrea Sagona, Alberto Bottini, Valentina Errico, Alberto Testori, Marta Scorsetti, Giuseppe Canavese, Corrado Tinterri. 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 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS4-05.

Abstract OT1-04-03: Sentinel lymph node biopsy versus no axillary surgery in early breast cancer clinically and ultrasonographically node negative: A multicentre prospective randomized controlled trial (VENUS trial)

Abstract Background: In early breast cancer, sentinel lymph node biopsy (SLNB) has become the gold standard of axillary evaluation. Although it has less morbidity than axillary lymph node dissection, it may still cause sequelae. Currently, patients selection for SNB has been through physical examination, but presents low sensitivity and high false negative rate. Thus, ultrasonography with biopsy of suspected lymph nodes increases the accuracy. In an attempt to further reduce the morbidity of axillary surgery, it was hypothesized that it would be possible to avoid SLNB in women with early breast cancer. The aim of this study is to compare the SLNB with no axillary surgery as an approach to the axilla in early breast cancer and negative axilla clinical and ultrasonographical. Our trial includes some subsets excluded in others similar ongoing trials: patients that will undergo mastectomy and will receive primary systemic therapy. Trial design: A multicenter, phase III, prospective, open-label, non-inferiority randomized clinical trial, including 10 study sites in Brazil that will randomize 800 early breast cancer patients.Eligibility criteria: Inclusion: woman, age ≥ 18 years, histologic diagnostic of breast carcinoma, tumor ≤ 5 cm (T1 and T2) in all exams, clinically node-negative, ultrasound node-negative or negative core biopsy/fine needle aspiration if suspect lymph node (in this situation is mandatory lymph node tissue in pathologic exam). Exclusion: metastatic disease in biopsy or image before treatment, pregnancy, breastfeed, previous diagnostic of invasive neoplasia (excluding skin cancer no melanoma). It will be allowed mastectomy and neoadjuvant treatment if patient has negative axilla and T1-2 pre-systemic therapy.Intervention and stratification: Participants in experimental group will not be undergo axillary surgery and in control group will be submitted at SLNB. The randomization will be 1:1 ratio and stratified by: tumor size (T1 and T2) and age (≥50 and &amp;lt; 50 years)Specific aims: the primary objective is to access whether omission of axillar surgery is not inferior than SLNB in term of disease-free survival (DFS) at 5 years (primary endpoint). Secondary endpoints are overall survival, locoregional free survival, axillary recurrence rate, to describe surgical early and later complications and to evaluate costs of procedure SLNB or no. Statistical methods: with type I error 5%, power 80% and risk ratio 0.8, considering DFS at 5 years 90% in control group non-inferior DFS at 5 years 85% in experimental group, it was calculated sample size of 400 patients randomized and with follow up in each group (lost estimated 10%). Chi-squares and Fisher's tests will be used for the univariate analyzes, and logistic regression models for adjusted analyzes. Disease-free survival analysis, disease-free survival at a distance, and overall survival will be performed, which will be compared between groups using Kaplan-Meyer curves, log-rank tests and Cox Proportional Hazards-adjusted analyzes. The analyzes will be made intention-to-treat and per protocol.Present and target accrual: the trial was activated at November 2019 and 92 patients were accrued on July 7th 2021. The estimative of finish recruitment is in 2025 and the first data analyses will be made in 2029. The trial is registered in ReBEC (Brazilian register): RBR-8g6jbf. Contact information: Prof. Dr. Giuliano Duarte, - Univertidade Estadual de Campinas - CAISM - UNICAMP, giulianomduarte@gmail.com Citation Format: Giuliano Mendes Duarte, Danielle Cristina Myiamoto Araújo, Rodrigo Menezes Jales, Júlia Yoriko Shinzato, Cassio Cardoso Filho, Renato Zocchio Torresan, Fabrício Palermo Brenelli, Maria Beatriz de PaulaLeite Kraft, Sergio Carlos Barros Esteves, Luis Otávio Zanatta Sarian, Rosemar MecedoSousa Rahal, Ruffo de Freitas, Jr, Eduardo Carvalho Pessoa, Clecio Ênio Murta Lucena, Andrea PiresSouto Damin, Jorge Villanova Biazus, Vinicius Milani Budel, Idan de Oliveira, Jr, Rene Aloisio da Costa Vieira, Júlio César Narciso Gomes. Sentinel lymph node biopsy versus no axillary surgery in early breast cancer clinically and ultrasonographically node negative: A multicentre prospective randomized controlled trial (VENUS trial) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-04-03.

Abstract OT1-04-04: AXSANA - EUBREAST 3 (axillary surgery after neoadjuvant treatment): An international prospective multicenter cohort study of the EUBREAST study group to evaluate different surgical methods of axillary staging (sentinel lymph node biopsy, targeted axillary dissection, axillary dissection) in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy (NCT04373655)

Abstract Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy alone (SLNB) are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study is initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with axillary lymph node metastasis and are scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ BR 23, Lymph ICF and SOC-13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: On June 30th 157 study sites from 15 countries are open for recruitment (Austria 2, Czech Republic 1, Finland 1, Germany 112, Greece 3, Italy 1, Norway 1, Poland 3, Portugal 5, Romania 2, Russia 1, Sweden 4, Switzerland 4, Spain 6, Turkey 11). 620 patients have been included in the study. Among patients who converted to ycN0 status, 144 have been scheduled for ALND, 157 for TAD and 49 for SLNB. The study is still open for further international study sites. Funding: AGO-B, Claudia-von Schilling Foundation, Ehmann Foundation, AWOgyn, Merit Medical, Endomagnetics, Mammotome Target accrual: 3000 patients worldwide Citation Format: Thorsten Kühn, Steffi Hartmann, Elmar Stickeler, Jana de Boniface, Oreste Gentilini, Sarah Fröhlich, Franziska Ruf, Marc Thill, Michael Hauptmann, Guldeniz Karadeniz Cakmak, Isabel Rubio, Maria Luisa Gasparri, Michaelis Kontos, Eduard-Alexandru Bonci, Laura Niinikoski, Rosa Di Micco, Dawid Murawa, David Pinto, Florentia Peintinger, Christine Solbach, Matilda Appelgren, Jens-Uwe Blohmer, Michael Weigel, Gabriele Kaltenecker, Michael Schrauder, Janine Simons, Marjolein Smidt, Ellen Schlichting, Lukas Dostalek, Alexander Sergeevich Emelyanov, Elisabeth Thiemann, Semra Gunay, Sybille Loibl, Maggie Banys-Paluchowski. AXSANA - EUBREAST 3 (axillary surgery after neoadjuvant treatment): An international prospective multicenter cohort study of the EUBREAST study group to evaluate different surgical methods of axillary staging (sentinel lymph node biopsy, targeted axillary dissection, axillary dissection) in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy (NCT04373655) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-04-04.

Abstract P3-19-08: Breast cancer related lymphedema in patients undergoing RNI: Is the axillary lateral vessel thoracic junction an organ-at-risk?

Abstract Background: Breast-cancer related lymphedema (BCRL) is a devastating treatment complication driven by the extent of axillary surgery (axillary lymph node dissection [ALND] versus sentinel lymph node biopsy [SLNB]). Regional nodal irradiation (RNI) may increase the risk of BCRL by up to 5%. Recently, investigators identified a region of the axilla known as the axillary-lateral thoracic vessel juncture (ALTJ) as a potential organ-at-risk (OAR) demonstrating that increasing radiation dose to the ALTJ was associated with a higher risk of BCRL. Here, we set to validate whether radiation dose to the ALTJ is associated with BCRL. Materials/Methods: We identified patients with stage II-III breast cancer treated with adjuvant RNI after M or L from 2013-2018 excluding those with BCRL pre-radiation. RNI treatment planning included delineation of clinical target volumes (CTVs): breast or chest wall and regional lymph nodes per the RTOG Breast Cancer Atlas. The CTVs were expanded by 5mm to create the planning target volume (PTV). Dose delivered was 50 Gy/25 fractions with goal of 47.5 Gy (95%) to 95% of each PTV. We defined BCRL as difference in arm circumference between the ipsilateral and contralateral limb &amp;gt;2.5 cm at any 1 visit or ≥2 cm on at least 2 visits. All patients suspected of having BCRL at routine follow-up visits were evaluated by physical therapy. The ALTJ was retrospectively contoured and the following metrics collected: maximum/minimum/mean dose; V10Gy-V50Gy. Follow-up time was defined as the time from surgery to the development of BCRL or last follow-up. Cox proportional hazards regression models were used to test the association between clinical and dosimetric parameters with the development of BCRL. All variables with p&amp;lt;0.10 on univariate analysis were entered in the final multivariate model (p&amp;lt;0.05 considered statistically significant). Results: Population includes 378 patients with median age 53 years (interquartile range [IQR], 45-61 years), median body mass index (BMI) 28.4 kg/m2 (IQR, 24.3-33.4 kg/m2), 60% HR+/HER2-, 89% chemotherapy, 53% stage III, 71% underwent M, and 82% underwent ALND with median of 18 nodes removed (IQR, 11-25) and median of 2+ nodes (IQR, 1-5). Median follow-up time was 54.5 months (IQR, 40.3-72.2 months). The ALTJ and axilla PTV overlapped in 91% of the patients. BCRL developed in 97 patients (25.7%) at a median of 18.9 months (IQR, 9.9-30.6 months). The 4-year cumulative incidence of BCRL was 23.5% (26.6% ALND vs. 8.7% SLNB, p=0.002). On univariate analysis, increasing age (HR=1.02, p=.039), increasing BMI (HR=1.04, p=0.002), increasing number of nodes removed (HR=1.04, p&amp;lt;0.0001), and use of IMRT vs. 3DCRT (HR=1.50, p=0.041) were all significantly associated with developing BCRL while increasing size of the axilla PTV (HR=0.96, p=0.047) was associated with a lower risk. None of the ALTJ metrics were associated with developing BCRL. Increasing ALTJ V45 was marginally associated with a lower risk of BCRL (HR=0.96, p=0.091). On multivariate analysis, increasing age (HR=1.02, p=0.021), increasing BMI (HR=1.04, p=0.004), and increasing number of nodes removed (HR=1.03, p=0.001) were associated with a higher risk of developing BCRL while use of IMRT (HR=1.24, p=0.338), size of the axilla PTV (HR=0.96, p=0.110) and ALTJ V45 (HR=0.99, p=0.708) were not. There were 10 local-regional recurrence (LRR) events as a first failure, 8 of which occurred with simultaneous distant metastases (DM). Of these LRRs, 5 included an axillary nodal component (all with DM) resulting in a 2.6% 4-year LRR rate (1.4% axillary recurrence rate). Conclusion: In this analysis, ALTJ is not validated as a critical OAR for reducing BCRL risk. Until such an OAR is discovered, the axillary PTV should not be modified or dose reduced in efforts to reduce BCRL given the low LRR and inability to validate ALTJ as an OAR. Citation Format: Erin Healy, Sachin Jhawar, Sasha Beyer, Julia R White, Jose G Bazan. Breast cancer related lymphedema in patients undergoing RNI: Is the axillary lateral vessel thoracic junction an organ-at-risk? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-08.

The Impact of an Incidental Dose on Axillary Tumor Control and Toxicity in Localized Breast Cancer: A Retrospective Analysis.

Simple SummaryThe incidental axillary dose varies according to the whole breast irradiation technique. However, this dose has not been shown to be a prognostic factor for locoregional recurrence. The objectives of our retrospective study are to dosimetrically evaluate the incidental axillary dose according to the different irradiation techniques and the risk factors of axillary recurrence. We confirmed that the irradiation technique has an influence on the incidental dose delivered to the axillary area, but has no influence on the risk of axillary recurrence. The risk of lymphoedema could be related to the use of high tangential beams and the mean dose delivered at level II.Purpose: The dosimetric analysis of the incidental axillary dose delivered to axillary lymph node levels I–III by different techniques of whole breast irradiation and the analysis of prognostic factors of axillary recurrence of breast cancer. Methods: We perform a retrospective analysis that includes 171 patients with localized breast carcinoma irradiated at Centre Paul Strauss. To be included in the study, patients had to have a histological confirmation of breast cancer diagnosis, surgical treatment without axillary lymph node dissection (ALND), whole breast irradiation without axillary irradiation by a specific field, and a treatment plan available. Results: Three patients had lymph node recurrence. There was no significant correlation between the maximal or mean dose delivered at the three axillary levels and the risk of axillary lymph node recurrence. There was no significant correlation between the irradiation technique and the risk of axillary lymph node recurrence. Two patients, both in the HT group, had lymphoedema. There was significantly more lymphoedema in the HT group than in the ST and IMRT groups (p < 0.048). The mean dose in level II was significantly higher in the group of patients with lymphoedema (3.45 Gy (1.08; 9.62) vs. 23.4 Gy (23.1; 23.6)) (p < 0.02). Conclusion: The irradiation technique has an influence on the incidental dose delivered to the axillary area, but has no influence on the risk of axillary recurrence. The risk of lymphoedema could be related to the use of HT and the mean dose delivered at level II.

Axillary Recurrence after Sentinel Node Biopsy for Early Stage Breast Cancer: Results from a Single Tertiary Institution in Manila, Philippines

Background: Sentinel node biopsy (SNB) is the procedure of choice for early breast cancer (BC) patients with clinically negative nodes. Veronesi et al proved that SNB provides an accurate representation of the patient’s true axillary status. The NSABP B-32 trial further confirmed that when the sentinel node is negative, SNB alone is an appropriate, effective and safe treatment for early BC. However, in the Philippine setting, due to concerns over oncologic safety and axillary recurrence, reluctance in the adoption of SNB occurred.

Recurrence and Survival Rates for 1400 Early Breast Tumors Treated with Intraoperative Radiation Therapy (IORT).

IntroductionIntraoperative radiotherapy (IORT) permits accurate delivery of radiation therapy directly to the tumor bed. We report local, regional, and distant recurrence data along with overall and breast cancer-specific survival for 1400 tumors treated with x-ray IORT.MethodsA total of 1367 patients with 1400 distinct tumors were enrolled in a registry trial. All received breast conservation surgery and low-energy 50 kV x-ray IORT. To be eligible for excision plus IORT as the only local treatment, histopathology had to confirm tumor size ≤30 mm, margins ≥2 mm, negative lymph nodes, and no extensive lymphovascular invasion. Patients who failed any parameters were referred for additional surgery and/or whole breast radiation therapy (WBRT).ResultsThere were 64 ipsilateral local recurrences, 60 were in the IORT only group, 7 axillary recurrences, and 7 distant recurrences. Forty-one local recurrences were within the same quadrant as the index cancer. Twenty-three were in different quadrants. With 62 months of median follow-up, the 5-year Kaplan–Meier probability of any event for all 1400 tumors was 5.27%. For 1175 patients who received IORT only, it was 5.98%. For favorable subtypes, it ranged from 2.41 to 4.31%. Multivariate analysis revealed that biologic subtype luminal A and the addition of WBRT significantly reduced the risk of local recurrence.ConclusionsThe local, regional, and distant recurrence rates observed were comparable to those reported in the literature for IORT but higher than those reported for standard forms of WBRT, hypofractionated treatment, or APBI. IORT benefits include convenience, decreased exposure to medical environments, and low complication rates.

The Usefulness of Ultrasound Surveillance for Axillary Recurrence in Women With Personal History of Breast Cancer.

PurposeTo evaluate the axillary recurrence rate and usefulness of axillary ultrasound (AUS) during supplementary whole-breast ultrasound (US) screening in women with a personal history of breast cancer (PHBC).MethodsA retrospective database search identified consecutive asymptomatic women who underwent postoperative supplemental whole-breast US screening, including that of the bilateral axillae, after negative findings on mammography between January and June 2017. Using the pathologic data or at least 1-year follow-up data as reference standards, the axillary recurrence rate, cancer detection rate (CDR), interval axillary recurrence rate per 1,000 screenings, sensitivity, specificity, and abnormal interpretation rate (AIR) were estimated.ResultsFrom the data of 4,430 women (mean age, 55.0 ± 10.1 years) analyzed in this study, there were five axillary recurrence cases (1.1/1,000) in the median follow-up period of 57.2 months. AUS showed a CDR of 0.2 (1/4,430; 95% confidence interval [CI], 0.01–1.3) and an interval axillary recurrence rate of 0.9 (4/4,402; 95% CI, 0.2–2.3) per 1,000 examinations. The sensitivity and specificity were 20.0% (1/5; 95% CI, 0.5–71.6), and 99.4% (4,398/4,425; 95% CI, 99.1–99.6), respectively, while the AIR was 0.6% (28/4,430; 95% CI, 0.4–0.9%).ConclusionIn asymptomatic women with a PHBC and negative findings on mammography, axillary recurrence after breast cancer and axillary treatment was uncommon, and the supplemental AUS screening yielded 0.2 cancers per 1,000 examinations.

Axillary Recurrence in Breast Cancer Patients After Negative Sentinel Lymph Node Biopsy: Retrospective Cohort Study From Riyadh, Saudi Arabia.

Breast cancer (BC) is among the most prevalent cancers globally. For minimally invasive axillary staging in early breast cancer, sentinel lymph node biopsy (SLNB) is commonly regarded as the gold standard. Historically, axillary lymph node dissection (ALND) was used as a staging procedure, but the less morbid SLNB has now replaced it. This retrospective cohort study, undertaken with patients at King Saud University Medical City in Riyadh, Saudi Arabia, evaluates mid-term follow-up data on axillary recurrences and outcomes for breast cancer patients with negative SLNB. The results indicate that the five-year risk of developing regional recurrence following negative SLNB is 0% in breast cancer patients. The low relapse rate further contributes to the evidence base suggesting the efficacy of SLNB and the higher morbidity associated with ALND. Future researchers should conduct a nationwide and long-term follow-up study to offer additional insights into the efficacy of SLNB.