Absence of post-treatment changes in sentinel lymph nodes does not translate into increased regional recurrence rate in initially node positive breast cancer patients

Absence of post-treatment changes in sentinel lymph nodes does not translate into increased regional recurrence rate in initially node positive breast cancer patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Absence of post-treatment changes in sentinel lymph nodes does not translate into increased regional recurrence rate in initially node positive breast cancer patients Nina Pislar, Gorana Gasljevic, Ivica Ratosa, Anja Kovac, Janez Zgajnar, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2967377/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Sep, 2023 Read the published version in Breast Cancer Research and Treatment → Version 1 posted 5 You are reading this latest preprint version Abstract Purpose: To determine whether the absence of post-treatment changes in the negative sentinel lymph nodes (SLN) in the neoadjuvant setting for biopsy-proven cN+ disease results in an increased regional recurrence (RR) rate in patients after SLN biopsy (SLNB) only. Methods: Breast cancer patients with biopsy-proven cN+ disease who converted to node-negative disease after neoadjuvant systemic treatment (NAST) and underwent SLNB only were included. Retrospective analysis was performed for patients diagnosed between 2008 and 2021. Patohistological specimens were reviewed for the presence of post-treatment changes in the SLNs. Patients with negative SLNs (ypN0) were divided into 2 groups: i) with post-treatment changes, ii) without post-treatment changes. Patients' characteristics were compared between groups. Crude RR rates were compared using the log-rank test. Recurrence-free (RFS) and overall survival (OS) for the entire cohort were calculated using Kaplan-Meier. Results: Of 437 patients with cN+ disease, 95 underwent SLNB only. 82 were ypN0, 57 with post-treatment changes (group 1), 30 without post-treatment changes (group 2). During the median follow-up of 37 months (range 6–148), 1 isolated regional recurrence occurred in group 2 (RR rate 0% for group 1 vs. 4% for group 2, p=0.167). 3-year RFS and 3-year OS were 90.2% and 96.3%, respectively. Conclusion: Absent post-treatment changes in negative SLNs for biopsy-proven cN+ disease that covert to node-negative after NAST did not result in increased regional recurrence rates in our cohort. Multidisciplinary input is essential to determine whether additional treatment is needed in these patients. breast cancer sentinel lymph node biopsy neoadjuvant post-treatment changes regional recurrence Figures Figure 1 Figure 2 Figure 3 Figure 4 1 Introduction In breast cancer patients with clinically node-positive disease at presentation (cN+), axillary lymph node dissection (ALND) may be avoided after neoadjuvant systemic treatment (NAST) [ 1 ]. Three multicenter prospective studies have shown that sentinel lymph node (SLN) biopsy is feasible with an acceptably low false-negative rate (FNR) in patients who convert to clinically node-negative disease after NAST (ycN0) when 3 or more SLNs are removed [ 2 – 4 ]. If metastatic nodal infiltration was biopsy-proven prior to NAST, we expect to detect vital metastases or some degree of treatment effect in the removed SLNs [ 5 ]. Post-treatment changes are recognized as nodal fibrosis, calcifications, mucin pools and foamy histiocyte aggregates on definite pathohistological examination [ 6 ]. If pathologic complete response (pCR) is achieved, post-treatment changes without residual metastases are observed, and if the response is partial, there are post-treatment changes with residual metastases [ 7 ]. In some patients with initial cN + disease, neither post-treatment changes nor metastases are detected in the SLNs after NAST, which may indicate that a false-negative lymph node was removed. If nodal pCR is recognized in SLNs, ALND can be omitted, whereas if residual metastases are detected, it is recommended to proceed with ALND [ 8 ]. If neither residual disease nor post-treatment changes are detected in SLNs, it is not clear whether ALND can be safely omitted. The aim of our study was to determine whether the absence of post-treatment changes in negative SLNs in biopsy-proven cN + disease results in an increased regional recurrence rate in patients after SLNB only. Secondary objective was to calculate recurrence-free survival (RFS) and overall survival (OS). 2 Methods After approval of the study by the National Ethics Committee (approval number 0120–178/2022/3), we retrospectively reviewed electronic patient records from the Institute of Oncology in Ljubljana, Slovenia. We collected data from patients consecutively diagnosed with breast cancer and referred to our institution between January 2008 and December 2021, who received NAST followed by surgery. Female patients with cT1-4 cN1-3 tumors were included. Patients with bilateral or inflammatory carcinoma, a history of invasive/non-invasive breast cancer, synchronous cancer at other sites and patients who were pregnant or had distant metastases at presentation were excluded. Positive cN status was determined by axillary ultrasound (AUS), and lymph nodes that met the criteria for suspicious/positive underwent fine-needle aspiration biopsy [ 9 ]. Only biopsy-confirmed nodal metastases were considered cN+. After NAST, axillary status was reevaluated by clinical palpation with/without AUS. Axillary surgery was planned according to national guidelines at that time; before the publication of the three prospective studies, patients with cN + disease rarely underwent SLNB and usually underwent ALND directly. In patients with cN + disease who converted to ycN0 after NAST, SLNB was planned after the practice was included in the national guidelines. At our institution, we perform SLNB after NAST in patients with initial cN + disease using the dual-tracer technique (technetium-labeled nano colloid and blue dye), without nodal clipping and remove 3 or more sentinel lymph nodes. We regularly use intraoperative touch imprint cytology (ITIC) and if the result is positive, we perform ALND during the same operation [ 10 ]. If lymphoscintigraphy is negative or we are unable to identify 3 or more SLNs, we proceed to ALND. Depending on definite pathohistological results, completion ALND is recommended if macro metastases are found in the SLNs. If SLNs contain isolated tumor cells (ITC) or micro metastases, the decision is made on a case-by-case basis in the multidisciplinary team (MDT) meeting. If SLNs are metastases-free, ALND can be omitted. If less than 3 SLNs are removed (inadequate SLNB), the decision to perform or omit completion ALND is made at the MDT meeting. Considering the initial clinical stage, radiotherapy (RT) of the nodal basins is recommended in the adjuvant setting, as well as adjuvant systemic treatment according to current guidelines. For this retrospective analysis, hematoxylin & eosin (H&E) sections and immunohistochemistry (IHC) of excised lymph nodes were reviewed by a single pathologist with expertise in breast pathology and reviewed for the presence/absence of post-treatment changes [ 6 ]. Patients who underwent SLNB only and were ypN0 (metastasis-free or with ITC) in the final pathohistological report were included in the present study. They were divided into 2 groups based on revised final pathohistological report: i) ypN0 with post-treatment changes and ii) ypN0 without post-treatment changes. Clinical and pathological characteristics were reported as median values with ranges for continuous variables and as absolute and relative frequencies for categorical variables. Baseline characteristics were compared between groups using the Mann-Whitney U test for continuous variables and the chi-square test for categorical variables. Regional recurrence was defined as a recurrence in ipsilateral axillary, supraclavicular or intramammary nodal basins. Local recurrence was defined as ipsilateral breast or chest wall recurrence. Distal recurrence was defined as any evidence of distant metastasis. Time to recurrence was calculated from the date of surgery. Patients were censored at the time of event, death, or last follow-up, whichever occurred first. Crude regional recurrence rates were compared between groups using the log-rank test. Kaplan-Meier curves were constructed to estimate RFS and OS. P values less than 0.05 were considered statistically significant. IBM SPSS Statistics for Windows (IBM Corp., Armonk, N.Y., USA) was used for the analysis. 3 Results We identified 437 patients with cN + disease who underwent NAST followed by surgery. In 203, upfront ALND was performed. In the remaining 234 patients, SLNB was planned. Forty-two of them underwent completion ALND during the same surgery because of a positive ITIC result, 45 underwent ALND due to unsuccessful SLNB, and 52 underwent completion ALND as a separate procedure (because of metastases in the SLNs or inadequate SLNB). SLNB only was performed in 95 patients, 82 of whom were ypN0 and eligible for analysis. Figure 1 shows a flow diagram for patient selection, and Fig. 2 shows how the ratio of ALND to SLNB changed over time. After reevaluation of the H&E and IHC slides, we identified 57 ypN0 patients with post-treatment changes (group 1) and 25 ypN0 patients without post-treatment changes (group 2). Clinical and pathological characteristics between groups are compared in Table 1 . Among 57 ypN0 patients in group 1, 10 patients contained ITC. Based on the initial pathohistological reports, 52 ypN0 patients had evidence of post-treatment changes and 30 ypN0 patients had no evidence of post-treatment changes. Table 1 Patients' clinical, pathological and treatment characteristics (Her-2 – human epidermal growth factor receptor 2, TN – triple negative, SLN – sentinel lymph node, BCS – breast conserving surgery, pCR – pathologic complete response, RT – radiation therapy) ypN0 with post-treatment changes N = 57 ypN0 without post-treatment changes N = 25 p Age in years , median (range) 50.1 (27–74) 46.4 (29–75) 0.248 Menopausal status Menopause 23 (40.4%) 8 (32.0%) 0.553 Pre/perimenopause 34 (57.6%) 16 (64.0%) Missing 1 (1.9%) Tumor size at presentation in mm , median (range) 33 (12–80) 30 (15–60) 0.336 Grade 2 23 (40.3) 9 (36.0%) 0.811 3 34 (59.7) 15 (60.0%) Missing 1 (4.0%) Histology Ductal 56 (98.2%) 24 (96.0%) 0.544 Lobular 1 (1.8%) 1 (4.0%) Subtype Luminal Her-2- 10 (17.5%) 6 (24.0%) 0.438 Her-2+ 36 (63.2%) 12 (48.0%) TN 11 (19.3%) 7 (28.0%) No. of SLN retrieved , median (range) 3.9 (2–9) 3.0 (1–6) 0.007 Proportion with < 3 SLNs removed 6 (11%) 9 (36%) 0.011 Breast surgery BCS 29 (55.8%) 14 (56.0%) 0.984 mastectomy 23 (44.2%) 11 (44.0%) Breast pCR (ypT0/Tis) 40 (76.9%) 14 (56.0%) 0.213 Received adjuvant RT 53 (93.0%) 24 (96.0%) 1.000 Regional recurrence 0 (0%) 1 (4.0%) 0.149 3.1 Regional recurrence During a median follow-up of 41 months (range 5–149 months) 1/25 (4%) isolated regional recurrence was observed in group 2 (ypN0 without post-treatment changes). This represents 1.2% of the total cohort (1/82). This patient underwent mastectomy with SLNB and had 3 SLNs removed at the initial surgery. All 3 SLNs were without post-treatment changes. She received adjuvant RT and tamoxifen. After 40 months, axillary nodal recurrence was confirmed. She underwent ALND with removal of 17 lymph nodes, 1 of which was positive. At 28 months after ALND, she remains disease-free. 3.2 Recurrence-free survival and overall survival A total of 8 recurrences were observed (1 local, 1 regional, 6 distant). One patient had a local recurrence after breast-conserving surgery at 13 months. She had refused adjuvant RT and chemotherapy. Six patients suffered isolated distant recurrences. The 3-year RFS was 90.2% (Fig. 3 ). Three patients died during the median follow-up of 43 months (range 8–149 months). The 3-year OS was 96.3% (Fig. 4 ). 4 Discussion Axillary management of initially node-positive patients who become node-negative after NAST remains controversial. However, with increasing evidence, the trend toward less invasive surgical procedures continues [ 11 , 12 ]. Over the years, the number of breast cancer patients receiving NAST has increased at our institution. In cN + patients converting to ycN0 after NAST, we have adopted SLNB with double tracer technique and at least 3 SLNs removed. The proportion of upfront ALNDs in our institution has decreased accordingly (85% upfront ALNDs in 2012–2013, 61% in 2015–2016, and 50% in 2020–2021). The main concer with SLNB in patients with cN + disease in the neoadjuvant setting remains the high FNR [ 13 ]. Although the purpose of axillary surgery is to both stage the axilla and remove any residual disease, it is unclear whether a higher FNR is actually associated with a higher regional recurrence rate and a worse prognosis. Detection of post-treatment changes in SLNs has been proposed as one of the principles for evaluating false negatives [ 6 ]. Brown et al. have shown that the absence of post-treatment changes in SLNs has a sensitivity of 82% and a specificity of 65% for detecting a false-negative SLN [ 14 ]. Post-treatment changes were present in 50% of SLNs, and the median number of SLNs removed was 2. In the study byBarrio et al, post-treatment changes were present in 88% of SLNs, and the median number of SLNs removed was 4 [ 15 ]. An alternative approach to assessing false negativity is clip placement at the time of initial nodal diagnostic biopsy. In the subgroup analysis of the Z1071 trial where a clip was used, it was identified in 75% of cases at SLNB only [ 16 ]. In our single-center retrospective study, post-treatment changes were identified in 70% of ypN0 patients (57/82) with a median of 3 SLNs removed. To our knowledge, we are the first to report the prognostic significance of absent post-treatment changes in SLNs in patients with biopsy-proven cN + disease undergoing NAST. The absence of post-treatment changes in SLNs did not translate into worse regional control in our cohort. According to the literature, post-treatment changes were detected in more than 90% of ALND specimens [ 15 ]. In addition to false negativity, the absence of post-treatment changes in SLNs may also be explained by failure to identify the changes by the pathologist and to nodal sampling. In the present study, the first problem was partially adressed by reevaluation of the original H&E and IHC slides. In our cohort of 82 patients with cN + disease who were ypN0 after SLNB only, there was only one (1.2%) isolated axillary recurrence during a median follow-up of 41 months. The regional recurrence rate in our cohort is within the range of previously published studies (0–1.6%) [ 11 , 17 – 20 ]. The patient with regional recurrence underwent salvage ALND and is disease free 28 months after ALND. Consistent with the study by Piltin et al, patients with ITC were classified as ypN0 in our study, although this is still controversial in the neoadjuvant setting [ 11 ]. Patients with ITC seem to have a better prognosis than patients with macrometastases, but it is not entirely clear whether they can be classified as pCR/ypN0 [ 20 – 22 ]. The ongoing ICARO study may provide additional clarity on the oncologic outcomes for patients with ITC who undergo ALND, nodal RT or observation only after SLNB. In women with cN + disease who respond well to NAST and are downstaged to ypN0, the role of RT in preventing locoregional recurrence is not entirely clear. The NSABP-51 trial will shed light on the role of adjuvant RT in reducing recurrence rates in these patients. In our clinical practice, the need for regional nodal RT has been determined primarily by the status of the axillary nodes prior to NAST, regardless of response to treatment (ypN0 or ypN1). In our study, the vast majority of patients received adjuvant RT (93% of patients with post-treatment changes and 96% of patients whithout post-treatment changes received adjuvant RT). Limitations of the current study include the retrospective nature of the study and a median follow-up time of only 41 months. However, it has been shown that the majority of nodal recurrences occur in a follow-up period of up to 5 years, so a longer follow-up period would not likely change the results significantly [ 18 , 23 , 24 ]. Although we follow the national guidelines for performing SLNB after NAST in patients with cN + disease, which include the use of dual tracers and removal of at least 3 SLNs, we do not follow a very strict protocol but decide on a case-by-case basis whether to omit or complete ALND in patients with less than 3 SLNs removed or absent post-treatment changes. Multidisciplinary input is essential to decide whether additional treatment is needed in these patients. The study allowed analysis of a single-center practice with many years of experience in the SLNB technique. Despite the relatively small number of patients included, this study adds to the short list of available studies on prognostic information for SLNB only after NAST in patients with cN + disease. To our knowledge, this is the first study to compare the oncologic outcomes of patients with cN + disease who convert to ycN0 and undergo SLNB only between patients with absent and present post-treatment changes in SLNs. 5 Conclusions In conclusion, absent post-treatment changes in negative SLNs in biopsy-proven node-positive disease converting to node-negative after NAST did not result in an increased regional recurrence rate in our study and should not be an indication for completion ALND in these patients. Longer follow-up is needed to further determine the oncologic safety of SLNB only in these patients. Declarations Funding The authors acknowledge the financial support from the Slovenian Research Agency (research core funding No. P3-0352 (C). Competing interests A.K. received honoraria from Novartis and Amgen, travel/accommodation expenses from MSD and Pfizer, sponsored lectures from Ewopharma and AstraZeneca. Other authors have no relevant financial or non-financial interests to disclose. Authors contribution A.P. and N.P. contributed to the study conception and design. Material preparation, data collection and analysis were performed by N.P., A.K. and G.G. The first draft was written by N.P. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Data availability The datasets generated and analysed during the current study are available from the corresponding author on reasonable request. 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Eur J Surg Oncol 42(3):361–8 Cite Share Download PDF Status: Published Journal Publication published 07 Sep, 2023 Read the published version in Breast Cancer Research and Treatment → Version 1 posted Reviewers agreed at journal 06 Jul, 2023 Reviewers invited by journal 30 May, 2023 Editor invited by journal 29 May, 2023 Editor assigned by journal 27 May, 2023 First submitted to journal 26 May, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2967377","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":205393573,"identity":"941ac671-cadd-4dbf-970f-55434b6e1de0","order_by":0,"name":"Nina Pislar","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxElEQVRIiWNgGAWjYFACxgaGBwwMcgwMbECOAYQirCWBgcGYFC1AANSS2ECkWgYGc+nm5g8JNffS+6XbEh8wFDDY8xHSYjnnYJtEwrHi3Jlzjh02ADossY2QFoMbQDUJbAm5G26kt0n/MQCyidACdNi/hHQDoBYJoC32xGhpkEhsS0gwuJF2DKSFkbDD7gD9ktiXYDhzRloy0C8SRPjldvvjDx++JcjzS6QZPmD4Y2Mv30BIjwReLjFaRsEoGAWjYBRgAgCRrDqlzmMt2wAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-6884-6526","institution":"Institute of Oncology Ljubljana: Onkoloski Institut Ljubljana","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Nina","middleName":"","lastName":"Pislar","suffix":""},{"id":205393574,"identity":"afa902d1-086f-4ae3-8435-74f439c019da","order_by":1,"name":"Gorana Gasljevic","email":"","orcid":"","institution":"Institute of Oncology Ljubljana: Onkoloski Institut Ljubljana","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Gorana","middleName":"","lastName":"Gasljevic","suffix":""},{"id":205393575,"identity":"68187874-917e-45f4-abcf-a0273a64d067","order_by":2,"name":"Ivica Ratosa","email":"","orcid":"","institution":"Institute of Oncology Ljubljana: Onkoloski Institut Ljubljana","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ivica","middleName":"","lastName":"Ratosa","suffix":""},{"id":205393576,"identity":"be355ec9-05d0-43eb-a82d-5af5632f6b6f","order_by":3,"name":"Anja Kovac","email":"","orcid":"","institution":"Institute of Oncology Ljubljana: Onkoloski Institut Ljubljana","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Anja","middleName":"","lastName":"Kovac","suffix":""},{"id":205393577,"identity":"2d5a498c-ea18-4db2-b3ee-4a71f8822a73","order_by":4,"name":"Janez Zgajnar","email":"","orcid":"","institution":"Institute of Oncology Ljubljana: Onkoloski Institut Ljubljana","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Janez","middleName":"","lastName":"Zgajnar","suffix":""},{"id":205393578,"identity":"7d92c167-4ecd-4e57-b5e4-4478497d61eb","order_by":5,"name":"Andraz Perhavec","email":"","orcid":"","institution":"Institute of Oncology Ljubljana: Onkoloski Institut Ljubljana","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Andraz","middleName":"","lastName":"Perhavec","suffix":""}],"badges":[],"createdAt":"2023-05-22 15:22:40","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2967377/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2967377/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10549-023-07084-x","type":"published","date":"2023-09-07T15:02:03+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":37870499,"identity":"bf7f9247-c811-4ed9-b530-f358ed1100e9","added_by":"auto","created_at":"2023-06-01 20:39:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":21923,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of patient selection according to axillary procedure (cN+ - clinically positive nodes before treatment, NAST - neoadjuvant systemic treatment, ALND - axillary lymph node dissection, SLNB - sentinel lymph node biopsy, ITIC - intraoperative touch imprint citology, ypN+ - positive nodes on pathology after neoadjuvant treatment, ypN0 – negative nodes on pathology after neoadjuvant treatment)\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-2967377/v1/d89ede917e01366e414d24cf.png"},{"id":37870501,"identity":"f4bf8512-1051-4ef3-a795-64a6607251bf","added_by":"auto","created_at":"2023-06-01 20:39:50","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":21817,"visible":true,"origin":"","legend":"\u003cp\u003eTime trends of axillary surgery for cN+à ycN0 patients after NAST between 2008-2021 according to primary surgery in axilla (ALND – axillary lymphadenectomy, SLNB – sentinel lymph node biopsy)\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-2967377/v1/dbdf6a2f434852fd4bdaa75c.png"},{"id":37870953,"identity":"5d7c492d-c36e-4a1d-80cc-71b28e641945","added_by":"auto","created_at":"2023-06-01 20:47:50","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":12419,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve of recurrence-free survival for ypN0 patients after sentinel node biopsy only\u003c/p\u003e","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-2967377/v1/96858cccb48132e9f9d7b699.png"},{"id":37870952,"identity":"77a93fa4-2022-4f3d-8b27-3efe0b3c0a37","added_by":"auto","created_at":"2023-06-01 20:47:50","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":11981,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve of overall survival for ypN0 patients after sentinel node biopsy only\u003c/p\u003e","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-2967377/v1/a24dbdba7b5dce74a56d6823.png"},{"id":42947407,"identity":"12ac0c94-6370-4028-bcf0-f759f38c5b4c","added_by":"auto","created_at":"2023-09-11 15:09:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":352371,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2967377/v1/93963cf0-6040-4c96-beb2-0007e85bd071.pdf"}],"financialInterests":"","formattedTitle":"Absence of post-treatment changes in sentinel lymph nodes does not translate into increased regional recurrence rate in initially node positive breast cancer patients","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eIn breast cancer patients with clinically node-positive disease at presentation (cN+), axillary lymph node dissection (ALND) may be avoided after neoadjuvant systemic treatment (NAST) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Three multicenter prospective studies have shown that sentinel lymph node (SLN) biopsy is feasible with an acceptably low false-negative rate (FNR) in patients who convert to clinically node-negative disease after NAST (ycN0) when 3 or more SLNs are removed [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIf metastatic nodal infiltration was biopsy-proven prior to NAST, we expect to detect vital metastases or some degree of treatment effect in the removed SLNs [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Post-treatment changes are recognized as nodal fibrosis, calcifications, mucin pools and foamy histiocyte aggregates on definite pathohistological examination [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. If pathologic complete response (pCR) is achieved, post-treatment changes without residual metastases are observed, and if the response is partial, there are post-treatment changes with residual metastases [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In some patients with initial cN\u0026thinsp;+\u0026thinsp;disease, neither post-treatment changes nor metastases are detected in the SLNs after NAST, which may indicate that a false-negative lymph node was removed. If nodal pCR is recognized in SLNs, ALND can be omitted, whereas if residual metastases are detected, it is recommended to proceed with ALND [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. If neither residual disease nor post-treatment changes are detected in SLNs, it is not clear whether ALND can be safely omitted. The aim of our study was to determine whether the absence of post-treatment changes in negative SLNs in biopsy-proven cN\u0026thinsp;+\u0026thinsp;disease results in an increased regional recurrence rate in patients after SLNB only. Secondary objective was to calculate recurrence-free survival (RFS) and overall survival (OS).\u003c/p\u003e"},{"header":"2 Methods","content":"\u003cp\u003e After approval of the study by the National Ethics Committee (approval number 0120\u0026ndash;178/2022/3), we retrospectively reviewed electronic patient records from the Institute of Oncology in Ljubljana, Slovenia. We collected data from patients consecutively diagnosed with breast cancer and referred to our institution between January 2008 and December 2021, who received NAST followed by surgery. Female patients with cT1-4 cN1-3 tumors were included. Patients with bilateral or inflammatory carcinoma, a history of invasive/non-invasive breast cancer, synchronous cancer at other sites and patients who were pregnant or had distant metastases at presentation were excluded. Positive cN status was determined by axillary ultrasound (AUS), and lymph nodes that met the criteria for suspicious/positive underwent fine-needle aspiration biopsy [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Only biopsy-confirmed nodal metastases were considered cN+.\u003c/p\u003e \u003cp\u003eAfter NAST, axillary status was reevaluated by clinical palpation with/without AUS. Axillary surgery was planned according to national guidelines at that time; before the publication of the three prospective studies, patients with cN\u0026thinsp;+\u0026thinsp;disease rarely underwent SLNB and usually underwent ALND directly. In patients with cN\u0026thinsp;+\u0026thinsp;disease who converted to ycN0 after NAST, SLNB was planned after the practice was included in the national guidelines. At our institution, we perform SLNB after NAST in patients with initial cN\u0026thinsp;+\u0026thinsp;disease using the dual-tracer technique (technetium-labeled nano colloid and blue dye), without nodal clipping and remove 3 or more sentinel lymph nodes. We regularly use intraoperative touch imprint cytology (ITIC) and if the result is positive, we perform ALND during the same operation [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. If lymphoscintigraphy is negative or we are unable to identify 3 or more SLNs, we proceed to ALND. Depending on definite pathohistological results, completion ALND is recommended if macro metastases are found in the SLNs. If SLNs contain isolated tumor cells (ITC) or micro metastases, the decision is made on a case-by-case basis in the multidisciplinary team (MDT) meeting. If SLNs are metastases-free, ALND can be omitted. If less than 3 SLNs are removed (inadequate SLNB), the decision to perform or omit completion ALND is made at the MDT meeting. Considering the initial clinical stage, radiotherapy (RT) of the nodal basins is recommended in the adjuvant setting, as well as adjuvant systemic treatment according to current guidelines.\u003c/p\u003e \u003cp\u003eFor this retrospective analysis, hematoxylin \u0026amp; eosin (H\u0026amp;E) sections and immunohistochemistry (IHC) of excised lymph nodes were reviewed by a single pathologist with expertise in breast pathology and reviewed for the presence/absence of post-treatment changes [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePatients who underwent SLNB only and were ypN0 (metastasis-free or with ITC) in the final pathohistological report were included in the present study. They were divided into 2 groups based on revised final pathohistological report: i) ypN0 with post-treatment changes and ii) ypN0 without post-treatment changes. Clinical and pathological characteristics were reported as median values with ranges for continuous variables and as absolute and relative frequencies for categorical variables. Baseline characteristics were compared between groups using the Mann-Whitney U test for continuous variables and the chi-square test for categorical variables.\u003c/p\u003e \u003cp\u003eRegional recurrence was defined as a recurrence in ipsilateral axillary, supraclavicular or intramammary nodal basins. Local recurrence was defined as ipsilateral breast or chest wall recurrence. Distal recurrence was defined as any evidence of distant metastasis. Time to recurrence was calculated from the date of surgery. Patients were censored at the time of event, death, or last follow-up, whichever occurred first. Crude regional recurrence rates were compared between groups using the log-rank test. Kaplan-Meier curves were constructed to estimate RFS and OS. P values less than 0.05 were considered statistically significant. IBM SPSS Statistics for Windows (IBM Corp., Armonk, N.Y., USA) was used for the analysis.\u003c/p\u003e"},{"header":"3 Results","content":"\u003cp\u003eWe identified 437 patients with cN\u0026thinsp;+\u0026thinsp;disease who underwent NAST followed by surgery. In 203, upfront ALND was performed. In the remaining 234 patients, SLNB was planned. Forty-two of them underwent completion ALND during the same surgery because of a positive ITIC result, 45 underwent ALND due to unsuccessful SLNB, and 52 underwent completion ALND as a separate procedure (because of metastases in the SLNs or inadequate SLNB). SLNB only was performed in 95 patients, 82 of whom were ypN0 and eligible for analysis. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows a flow diagram for patient selection, and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows how the ratio of ALND to SLNB changed over time.\u003c/p\u003e \u003cp\u003eAfter reevaluation of the H\u0026amp;E and IHC slides, we identified 57 ypN0 patients with post-treatment changes (group 1) and 25 ypN0 patients without post-treatment changes (group 2). Clinical and pathological characteristics between groups are compared in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Among 57 ypN0 patients in group 1, 10 patients contained ITC. Based on the initial pathohistological reports, 52 ypN0 patients had evidence of post-treatment changes and 30 ypN0 patients had no evidence of post-treatment changes.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatients' clinical, pathological and treatment characteristics (Her-2 \u0026ndash; human epidermal growth factor receptor 2, TN \u0026ndash; triple negative, SLN \u0026ndash; sentinel lymph node, BCS \u0026ndash; breast conserving surgery, pCR \u0026ndash; pathologic complete response, RT \u0026ndash; radiation therapy)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eypN0 with post-treatment changes\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;57\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eypN0 without post-treatment changes\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;25\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge in years\u003c/b\u003e, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.1 (27\u0026ndash;74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.4 (29\u0026ndash;75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.248\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMenopausal status\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMenopause\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (40.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (32.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.553\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePre/perimenopause\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (57.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (64.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMissing\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumor size at presentation in mm\u003c/b\u003e, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (12\u0026ndash;80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (15\u0026ndash;60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.336\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGrade\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (40.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (36.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.811\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e3\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (59.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMissing\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eDuctal\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (98.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (96.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.544\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLobular\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSubtype\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLuminal Her-2-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (17.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (24.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.438\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eHer-2+\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (63.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (48.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTN\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (19.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (28.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo. of SLN retrieved\u003c/b\u003e, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.9 (2\u0026ndash;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.0 (1\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.007\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProportion with \u0026lt;\u0026thinsp;3 SLNs removed\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (11%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.011\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBreast surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBCS\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (55.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (56.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.984\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003emastectomy\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (44.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (44.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBreast pCR (ypT0/Tis)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (76.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (56.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.213\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReceived adjuvant RT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (93.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (96.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRegional recurrence\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.149\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Regional recurrence\u003c/h2\u003e \u003cp\u003eDuring a median follow-up of 41 months (range 5\u0026ndash;149 months) 1/25 (4%) isolated regional recurrence was observed in group 2 (ypN0 without post-treatment changes). This represents 1.2% of the total cohort (1/82). This patient underwent mastectomy with SLNB and had 3 SLNs removed at the initial surgery. All 3 SLNs were without post-treatment changes. She received adjuvant RT and tamoxifen. After 40 months, axillary nodal recurrence was confirmed. She underwent ALND with removal of 17 lymph nodes, 1 of which was positive. At 28 months after ALND, she remains disease-free.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Recurrence-free survival and overall survival\u003c/h2\u003e \u003cp\u003eA total of 8 recurrences were observed (1 local, 1 regional, 6 distant). One patient had a local recurrence after breast-conserving surgery at 13 months. She had refused adjuvant RT and chemotherapy. Six patients suffered isolated distant recurrences. The 3-year RFS was 90.2% (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThree patients died during the median follow-up of 43 months (range 8\u0026ndash;149 months). The 3-year OS was 96.3% (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eAxillary management of initially node-positive patients who become node-negative after NAST remains controversial. However, with increasing evidence, the trend toward less invasive surgical procedures continues [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Over the years, the number of breast cancer patients receiving NAST has increased at our institution. In cN\u0026thinsp;+\u0026thinsp;patients converting to ycN0 after NAST, we have adopted SLNB with double tracer technique and at least 3 SLNs removed. The proportion of upfront ALNDs in our institution has decreased accordingly (85% upfront ALNDs in 2012\u0026ndash;2013, 61% in 2015\u0026ndash;2016, and 50% in 2020\u0026ndash;2021).\u003c/p\u003e \u003cp\u003eThe main concer with SLNB in patients with cN\u0026thinsp;+\u0026thinsp;disease in the neoadjuvant setting remains the high FNR [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Although the purpose of axillary surgery is to both stage the axilla and remove any residual disease, it is unclear whether a higher FNR is actually associated with a higher regional recurrence rate and a worse prognosis. Detection of post-treatment changes in SLNs has been proposed as one of the principles for evaluating false negatives [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Brown et al. have shown that the absence of post-treatment changes in SLNs has a sensitivity of 82% and a specificity of 65% for detecting a false-negative SLN [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Post-treatment changes were present in 50% of SLNs, and the median number of SLNs removed was 2. In the study byBarrio et al, post-treatment changes were present in 88% of SLNs, and the median number of SLNs removed was 4 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. An alternative approach to assessing false negativity is clip placement at the time of initial nodal diagnostic biopsy. In the subgroup analysis of the Z1071 trial where a clip was used, it was identified in 75% of cases at SLNB only [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our single-center retrospective study, post-treatment changes were identified in 70% of ypN0 patients (57/82) with a median of 3 SLNs removed. To our knowledge, we are the first to report the prognostic significance of absent post-treatment changes in SLNs in patients with biopsy-proven cN\u0026thinsp;+\u0026thinsp;disease undergoing NAST. The absence of post-treatment changes in SLNs did not translate into worse regional control in our cohort.\u003c/p\u003e \u003cp\u003eAccording to the literature, post-treatment changes were detected in more than 90% of ALND specimens [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In addition to false negativity, the absence of post-treatment changes in SLNs may also be explained by failure to identify the changes by the pathologist and to nodal sampling. In the present study, the first problem was partially adressed by reevaluation of the original H\u0026amp;E and IHC slides.\u003c/p\u003e \u003cp\u003eIn our cohort of 82 patients with cN\u0026thinsp;+\u0026thinsp;disease who were ypN0 after SLNB only, there was only one (1.2%) isolated axillary recurrence during a median follow-up of 41 months. The regional recurrence rate in our cohort is within the range of previously published studies (0\u0026ndash;1.6%) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The patient with regional recurrence underwent salvage ALND and is disease free 28 months after ALND.\u003c/p\u003e \u003cp\u003eConsistent with the study by Piltin et al, patients with ITC were classified as ypN0 in our study, although this is still controversial in the neoadjuvant setting [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Patients with ITC seem to have a better prognosis than patients with macrometastases, but it is not entirely clear whether they can be classified as pCR/ypN0 [\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The ongoing ICARO study may provide additional clarity on the oncologic outcomes for patients with ITC who undergo ALND, nodal RT or observation only after SLNB.\u003c/p\u003e \u003cp\u003eIn women with cN\u0026thinsp;+\u0026thinsp;disease who respond well to NAST and are downstaged to ypN0, the role of RT in preventing locoregional recurrence is not entirely clear. The NSABP-51 trial will shed light on the role of adjuvant RT in reducing recurrence rates in these patients. In our clinical practice, the need for regional nodal RT has been determined primarily by the status of the axillary nodes prior to NAST, regardless of response to treatment (ypN0 or ypN1). In our study, the vast majority of patients received adjuvant RT (93% of patients with post-treatment changes and 96% of patients whithout post-treatment changes received adjuvant RT).\u003c/p\u003e \u003cp\u003eLimitations of the current study include the retrospective nature of the study and a median follow-up time of only 41 months. However, it has been shown that the majority of nodal recurrences occur in a follow-up period of up to 5 years, so a longer follow-up period would not likely change the results significantly [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Although we follow the national guidelines for performing SLNB after NAST in patients with cN\u0026thinsp;+\u0026thinsp;disease, which include the use of dual tracers and removal of at least 3 SLNs, we do not follow a very strict protocol but decide on a case-by-case basis whether to omit or complete ALND in patients with less than 3 SLNs removed or absent post-treatment changes. Multidisciplinary input is essential to decide whether additional treatment is needed in these patients.\u003c/p\u003e \u003cp\u003eThe study allowed analysis of a single-center practice with many years of experience in the SLNB technique. Despite the relatively small number of patients included, this study adds to the short list of available studies on prognostic information for SLNB only after NAST in patients with cN\u0026thinsp;+\u0026thinsp;disease. To our knowledge, this is the first study to compare the oncologic outcomes of patients with cN\u0026thinsp;+\u0026thinsp;disease who convert to ycN0 and undergo SLNB only between patients with absent and present post-treatment changes in SLNs.\u003c/p\u003e"},{"header":"5 Conclusions","content":"\u003cp\u003eIn conclusion, absent post-treatment changes in negative SLNs in biopsy-proven node-positive disease converting to node-negative after NAST did not result in an increased regional recurrence rate in our study and should not be an indication for completion ALND in these patients. Longer follow-up is needed to further determine the oncologic safety of SLNB only in these patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge the financial support from the Slovenian Research Agency (research core funding No. P3-0352 (C).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eA.K. received honoraria from Novartis and Amgen, travel/accommodation expenses from MSD and Pfizer, sponsored lectures from Ewopharma and AstraZeneca.\u003c/p\u003e\n\u003cp\u003eOther authors have no relevant financial or non-financial interests to disclose.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAuthors contribution\u003c/p\u003e\n\u003cp\u003eA.P. and N.P. contributed to the study conception and design. Material preparation, data collection and analysis were performed by N.P., A.K. and G.G. The first draft was written by N.P. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData availability\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMamtani A, Barrio AV, King TA, et al (2016) How Often Does Neoadjuvant Chemotherapy Avoid Axillary Dissection in Patients With Histologically Confirmed Nodal Metastases? Results of a Prospective Study. Ann Surg Oncol 23(11):3467\u0026ndash;74\u003c/li\u003e\n\u003cli\u003eKuehn T, Bauerfeind I, Fehm T, et al (2013) Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): A prospective, multicentre cohort study. Lancet Oncol 14(7):609\u0026ndash;18\u003c/li\u003e\n\u003cli\u003eBoileau JF, Poirier B, Basik M, et al (2015) Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: The SN FNAC study. J Clin Oncol 33(3):258\u0026ndash;63\u003c/li\u003e\n\u003cli\u003eBoughey JC, Suman VJ, Mittendorf EA, et al (2013) Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: The ACOSOG Z1071 (alliance) clinical trial. JAMA 310(14):1455\u0026ndash;61\u003c/li\u003e\n\u003cli\u003eNathanson SD, Krag D, Kuerer HM, et al (2018) Breast cancer metastasis through the lympho-vascular system. Clin Exp Metastasis 35(5\u0026ndash;6):443\u0026ndash;54\u003c/li\u003e\n\u003cli\u003eNewman LA, Pernick NL, Adsay V, et al (2003) Histopathologic evidence of tumor regression in the axillary lymph nodes of patients treated with preoperative chemotherapy correlates with breast cancer outcome. Ann Surg Oncol 10(7):734\u0026ndash;9\u003c/li\u003e\n\u003cli\u003eGlaeser A, Sinn HP, Garcia-Etienne C, et al (2019) Heterogeneous Responses of Axillary Lymph Node Metastases to Neoadjuvant Chemotherapy are Common and Depend on Breast Cancer Subtype. Ann Surg Oncol. 26(13):4381\u0026ndash;9\u003c/li\u003e\n\u003cli\u003eRiogi B, Sripadam R, Barker D, et al (2021) Management of the axilla following neoadjuvant chemotherapy for breast cancer- A change in practice. Surgeon 19(1):1\u0026ndash;7\u003c/li\u003e\n\u003cli\u003ePodkrajsek M, Music MM, Kadivec M, et al (2005) Role of ultrasound in the preoperative staging of patients with breast cancer. Eur Radiol 15(5):1044\u0026ndash;50\u003c/li\u003e\n\u003cli\u003eHadalin V, Pislar N, Borstnar S, et al (2022) Intraoperative Touch Imprint Cytology in Breast Cancer Patients After Neoadjuvant Chemotherapy. Clin Breast Cancer 22(4):e597\u0026ndash;603 \u003c/li\u003e\n\u003cli\u003ePiltin MA, Hoskin TL, Day CN, Davis J, Boughey JC (2020) Oncologic Outcomes of Sentinel Lymph Node Surgery After Neoadjuvant Chemotherapy for Node-Positive Breast Cancer. Ann Surg Oncol 27(12):4795\u0026ndash;801\u003c/li\u003e\n\u003cli\u003eNguyen TT, Hoskin TL, et al (2018) Decreasing Use of Axillary Dissection in Node-Positive Breast Cancer Patients Treated with Neoadjuvant Chemotherapy. Ann Surg Oncol 25(9):2596\u0026ndash;602\u003c/li\u003e\n\u003cli\u003eCao S, Liu X, Cui J, et al (2021) Feasibility and reliability of sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer patients with positive axillary nodes at initial diagnosis: An up-to date meta-analysis of 3,578 patients. Breast 59:256\u0026ndash;69\u003c/li\u003e\n\u003cli\u003eBrown AS, Hunt KK, Shen J, et al (2010) Histologic changes associated with false-negative sentinel lymph nodes after preoperative chemotherapy in patients with confirmed lymph node-positive breast cancer before treatment. Cancer 116(12):2878\u0026ndash;83\u003c/li\u003e\n\u003cli\u003eBarrio AV, Mamtani A, Edelweiss M, et al (2016) How Often Is Treatment Effect Identified in Axillary Nodes with a Pathologic Complete Response After Neoadjuvant Chemotherapy? Ann Surg Oncol 23(11):3475\u0026ndash;80\u003c/li\u003e\n\u003cli\u003eBoughey JC, Ballman K V., Le-Petross HT, et al (2016) Identification and resection of clipped node decreases the false-negative rate of sentinel lymph node surgery in patients presenting with node-positive breast cancer (T0-T4, N1-N2) Who receive neoadjuvant chemotherapy: Results from ACO SOG Z107 1 (Alliance). Ann Surg 263(4):802\u0026ndash;7\u003c/li\u003e\n\u003cli\u003eBarrio AV, Montagna G, Mamtani A, et al (2021) Nodal Recurrence in Patients with Node-Positive Breast Cancer Treated with Sentinel Node Biopsy Alone after Neoadjuvant Chemotherapy - A Rare Event. JAMA Oncol 7(12):1851\u0026ndash;5\u003c/li\u003e\n\u003cli\u003eKahler-Ribeiro-Fontana S, Pagan E, Magnoni F, et al (2021) Long-term standard sentinel node biopsy after neoadjuvant treatment in breast cancer: a single institution ten-year follow-up. Eur J Surg Oncol 47(4):804\u0026ndash;12\u003c/li\u003e\n\u003cli\u003eWong SM, Basik M, Florianova L, et al (2021) Oncologic Safety of Sentinel Lymph Node Biopsy Alone After Neoadjuvant Chemotherapy for Breast Cancer. Ann Surg Oncol 28(5):2621\u0026ndash;9\u003c/li\u003e\n\u003cli\u003eTercan IC, Zengel B, Ozdemir O, et al (2023) The Oncologic Safety of Sentinel Lymph Node Biopsy in Patients with Node-Positive Breast Cancer with Complete Response to Neoadjuvant Chemotherapy: A Single-Center Experience. Breast J 2023\u003c/li\u003e\n\u003cli\u003evan Nijnatten TJA, Simons JM, Moossdorff M, et al (2017) Prognosis of residual axillary disease after neoadjuvant chemotherapy in clinically node-positive breast cancer patients: isolated tumor cells and micrometastases carry a better prognosis than macrometastases. Breast Cancer Res Treat 163(1):159\u0026ndash;66\u003c/li\u003e\n\u003cli\u003eWong SM, Almana N, Choi J, et al (2019) Prognostic Significance of Residual Axillary Nodal Micrometastases and Isolated Tumor Cells After Neoadjuvant Chemotherapy for Breast Cancer. Ann Surg Oncol 26(11):3502\u0026ndash;9\u003c/li\u003e\n\u003cli\u003eGiuliano AE, Ballman KV, McCall L, et al (2017) Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA 318(10):918\u0026ndash;26\u003c/li\u003e\n\u003cli\u003eGalimberti V, Ribeiro Fontana SK, Maisonneuve P, et al (2016) Sentinel node biopsy after neoadjuvant treatment in breast cancer: Five-year follow-up of patients with clinically node-negative or node-positive disease before treatment. Eur J Surg Oncol 42(3):361\u0026ndash;8\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"breast-cancer-research-and-treatment","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brea","sideBox":"Learn more about [Breast Cancer Research and Treatment](https://www.springer.com/journal/10549)","snPcode":"10549","submissionUrl":"https://submission.nature.com/new-submission/10549/3","title":"Breast Cancer Research and Treatment","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"breast cancer, sentinel lymph node biopsy, neoadjuvant, post-treatment changes, regional recurrence","lastPublishedDoi":"10.21203/rs.3.rs-2967377/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2967377/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e To determine whether the absence of post-treatment changes in the negative sentinel lymph nodes (SLN) in the neoadjuvant setting for biopsy-proven cN+ disease results in an increased regional recurrence (RR) rate in patients after SLN biopsy (SLNB) only.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Breast cancer patients with biopsy-proven cN+ disease who converted to node-negative disease after neoadjuvant systemic treatment (NAST) and underwent SLNB only were included. Retrospective analysis was performed for patients diagnosed between 2008 and 2021. Patohistological specimens were reviewed for the presence of post-treatment changes in the SLNs. Patients with negative SLNs (ypN0) were divided into 2 groups: i) with post-treatment changes, ii) without post-treatment changes. Patients' characteristics were compared between groups. Crude RR rates were compared using the log-rank test. Recurrence-free (RFS) and overall survival (OS) for the entire cohort were calculated using Kaplan-Meier.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eOf 437 patients with cN+ disease, 95 underwent SLNB only. 82 were ypN0, 57 with post-treatment changes (group 1), 30 without post-treatment changes (group 2). During the median follow-up of 37 months (range 6–148), 1 isolated regional recurrence occurred in group 2 (RR rate 0% for group 1 vs. 4% for group 2, p=0.167). 3-year RFS and 3-year OS were 90.2% and 96.3%, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Absent post-treatment changes in negative SLNs for biopsy-proven cN+ disease that covert to node-negative after NAST did not result in increased regional recurrence rates in our cohort. Multidisciplinary input is essential to determine whether additional treatment is needed in these patients.\u003c/p\u003e","manuscriptTitle":"Absence of post-treatment changes in sentinel lymph nodes does not translate into increased regional recurrence rate in initially node positive breast cancer patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-06-01 20:39:45","doi":"10.21203/rs.3.rs-2967377/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2023-07-06T13:55:28+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-05-31T01:40:24+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Breast Cancer Research and Treatment","date":"2023-05-29T18:11:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-05-27T04:53:52+00:00","index":"","fulltext":""},{"type":"submitted","content":"Breast Cancer Research and Treatment","date":"2023-05-26T08:18:06+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"breast-cancer-research-and-treatment","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brea","sideBox":"Learn more about [Breast Cancer Research and Treatment](https://www.springer.com/journal/10549)","snPcode":"10549","submissionUrl":"https://submission.nature.com/new-submission/10549/3","title":"Breast Cancer Research and Treatment","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"dce37e4a-a092-4326-a7c7-d2cd4dfca10e","owner":[],"postedDate":"June 1st, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-09-11T15:07:28+00:00","versionOfRecord":{"articleIdentity":"rs-2967377","link":"https://doi.org/10.1007/s10549-023-07084-x","journal":{"identity":"breast-cancer-research-and-treatment","isVorOnly":false,"title":"Breast Cancer Research and Treatment"},"publishedOn":"2023-09-07 15:02:03","publishedOnDateReadable":"September 7th, 2023"},"versionCreatedAt":"2023-06-01 20:39:45","video":"","vorDoi":"10.1007/s10549-023-07084-x","vorDoiUrl":"https://doi.org/10.1007/s10549-023-07084-x","workflowStages":[]},"version":"v1","identity":"rs-2967377","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2967377","identity":"rs-2967377","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}