Correlation between sentinel lymph node biopsy and non-sentinel lymph node metastasis in patients with cN0 breast carcinoma: comparison of invasive ductal carcinoma and invasive lobular carcinoma

Correlation between sentinel lymph node biopsy and non-sentinel lymph node metastasis in patients with cN0 breast carcinoma: comparison of invasive ductal carcinoma and invasive lobular carcinoma | 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 Correlation between sentinel lymph node biopsy and non-sentinel lymph node metastasis in patients with cN0 breast carcinoma: comparison of invasive ductal carcinoma and invasive lobular carcinoma Calogero Cipolla, Simona Lupo, Nello Grassi, Giuseppe Tutino, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3860683/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background : Recent studies have suggested that axillary lymph node dissection (ALND) can be avoided in women with cN0 breast cancer with 1-2 positive sentinel nodes (SLNs). However, these studies included only a few patients with invasive lobular carcinoma (ILC), so the validity of omitting ALDN in these patients remains controversial. This study compared the frequency of non-sentinel lymph nodes (non-SLNs) metastases in ILC and invasive ductal carcinoma (IDC). Materials Methods: Data relating to a total of 2583 patients with infiltrating breast carcinoma operated at our institution between 2012 and 2023 were retrospectively analyzed: 2242 (86.8%) with IDC and 341 (13.2%) with ILC. We compared the incidence of metastasis to SLNs and non-SLNs between the ILC and IDC cohorts and examined factors that influenced non-SLNs metastasis. Results : SLN biopsies were performed in 315 patients with ILC and 2018 patients with IDC. Metastases to the SLNs were found in 78/315 (24.8%) patients with ILC and in 460 (22.8%) patients with IDC (p= 0.31). The incidence of metastases to non-SLNs was significantly higher (p = 0.02) in ILC (52/78 - 66.7%) compared to IDC (207/460 - 45%). Multivariate analysis showed that ILC was the most influential predictive factor in predicting the presence of metastasis to non-SLNs. Conclusions : ILC cases have more non-SLNs metastases than IDC cases in SLN-positive patients. The ILC is essential for predicting non-SLN positivity in macro-metastases in the SLN. The option of omitting ALND in patients with ILC with 1-2 positive SLNs still requires further investigation. Breast carcinoma infiltrating lobular carcinoma Infiltrating ductal carcinoma Sentinel lymph node biopsy Nonsentinel lymph node metastasis Axillary lymphadenectomy Figures Figure 1 1. Introduction Sentinel lymph node biopsy (SLNB) has now been confirmed as a standard surgical procedure for staging the axilla in patients with early breast cancer (BC) and clinically negative lymph nodes (cN0), limiting the use of axillary lymph node dissection (ALND) to patients with positive SLNs ( 1 , 2 ). However, positivity in non-SLNs is only found in approximately 34–50% of patients with positive SLNs undergoing completion of ALND ( 3 ). The ACOSOG Z0011 study demonstrated that omitting ALND in cT1-2 cN0 cM0 patients with 1–2 positive SLNs resulted in a non-inferior outcome compared to patients undergoing ALND ( 4 ). However, patients with invasive ductal carcinoma (IDC) constitute more than 80% of the ACOSOG Z0011 study population. For this reason, some questions have been raised about applying its findings to other histological types, particularly invasive lobular carcinoma (ILC). Although ILC represents only approximately 5–10% of all BC, its immunophenotypic characteristics, clinical course, and therapy response present unique aspects that require particular attention. ILC more frequently shows positivity for hormone receptors and little or no expression for human epidermal growth factor receptor-2 (HER2) compared to IDC. The response to chemotherapy is significantly lower than that of IDC ( 5 – 8 ). Recent studies have shown that ILC has a similar rate of metastasis to non-SLNs compared to IDC, thus supporting the idea that applying the ACOSOG Z0011 criteria is safe even in patients with ILC ( 9 , 10 ). However, information regarding the implementation of SLNB in ​​patients with ILC is still scarce, and the question remains unclear whether patients with ILC and 1–2 positive SLNs can be exempted from ALND ( 10 – 12 ) without effects on survival. In this study, we retrospectively compared the rates of metastatic lymph node involvement in non-SLNs between patients with IDC and those with ILC, intending to offer a further contribution to the question of whether the ACOSOG Z0011 trial criteria can also be safely applied to patients with ILC. 2. Materials and Methods Study design After approval by the Institutional Review Board of the University Hospital AUOP Paolo Giaccone of Palermo, we collected and retrospectively analyzed the clinical records of an extensive series of patients with cN0 primary invasive BC observed at our institution between 2012 and 2023. The aim of this retrospective study was to compare the rates of metastatic lymph node involvement in non-SLNs between patients with IDC and those with ILC to confirm of the ACOSOG Z0011 trial criteria can also be safely applied to patients with ILC. Inclusion and exclusion criteria. Data relating to patients with IDC and ILC who underwent SLNB were included in the study. Exclusion criteria from the study were previous neoadjuvant therapy, inflammatory BC, locally recurrent BC, metastatic disease at the diagnosis, and lack of complete data. In all cases, the diagnosis of BC was made using a percutaneous biopsy with a 14G tru-cut needle or a vacuum-assisted breast biopsy with a 7G cannula ( 13 ). Histopathological diagnoses of ILC and IDC were made with hematoxylin-eosin staining. Furthermore, the expressivity of the hormone receptors for estrogen and progesterone and HER-2 and the Ki-67 cell proliferation index were evaluated. Tumors were then classified based on molecular subtypes. The diagnosis of IDC was confirmed by positive immunohistochemical staining for E-cadherin. Clinical evaluation of the axilla was performed with clinical examination, ultrasound, and cytological examination using FNAC of the suspicious lymph nodes. Women with clinically negative axillary lymph nodes underwent SLNB. The SLN was detected using the radiotracer identification technique and, if necessary, using vital dye, as described in our previous studies ( 14 – 16 ). All patients underwent synchronous breast cancer excision by breast-conserving surgery or total mastectomy and SLNB. The recovered SLNs were analyzed during surgery using frozen section (FS) histological examination. All SLNs were subsequently examined with definitive histopathological examination complete with immunohistochemistry ( 16 ). In cases where suspicious non-SLNs were present on intraoperative palpation of the axilla, these were removed at the same time as the SLNB and sent separately to the FS for histological examination. ALND was not performed in patients with negative SLN, isolated tumor cells (ITC), or micrometastases. In the case of macrometastases at FS in the SLN or in any non-SLN removed simultaneously, the patients immediately underwent completion ALND. In cases of SLN or non-SLNs negative at FS but positive for macrometastases at the definitive histopathological examination, ALND was completed in a second operation. Statistical analysis Differences between the two patient cohorts were calculated using the χ2 test. The statistical significance limit was defined as a p-value < 0.05. A logistic regression analysis was performed to examine the factors that influenced the presence of metastases to non-SLNs when the SLN had macro-metastases. 3. Results The clinical records of 2583 patients with infiltrating BC operated between 2012 and 2023 were evaluated: 2242 (86.8%) with IDC and 341 (13.2%) with ILC. Two hundred twenty-four patients with IDC and 26 patients with ILC were excluded from the study as they initially underwent ALND. Ultimately, 2333 patients were included in the study, of which 2018 (86.4%) had IDC and 315 (13.5%) had ILC. Patients’ population The clinical and pathological characteristics of the two cohorts of patients are summarized in Table 1. Patients with ILC were older at diagnosis than those with IDC (p < 0.01). The Luminal A molecular subtype was the most represented in ILC compared to IDC, unlike the HER2-enriched and Triple Negative subtypes, which were lower in ILC than DCI (p < 0.001). Furthermore, ILCs were found to have a larger diameter (p<0.01) and a higher histological grade (p<0.01) compared to IDCs. The presence of metastases in the SLN was found in 93 patients (29.5%) with ILC; 15 cases were excluded as they were micrometastases, and in the end, a macrometastases was found in 78 of the 315 patients (24.8%) with ILC. The presence of metastases in the SLN was found in 607 patients (30%) with IDC; 147 cases were excluded as they were micrometastases, and ultimately, a macrometastases was found in 460 of the 2018 patients (22.8%) with ILC. The difference between the two groups was not significant (p 0.31). Metastases to non-SLNs were found in 52/78 patients (66.7%) with ILC and in 207/460 patients (45%) with positive SLNs and undergoing completion ALND, with a statistically significant difference between the two groups (p = 0.02). The data are summarized in Figure 1. Furthermore, as can be seen in Table 2, the number of metastatic non-SLNs was more significant in ILC compared to IDC. The multivariate analysis also showed that in patients with macrometastases in the SLN, in addition to the number of positive SLNs, the ILC histotype represents the most influential factor in predicting the presence of metastases in non-SLNs concerning age, tumor size, grade histological and molecular subtype (Table 3). 4. Discussion In our study, patients with ILC had a higher mean age, larger tumor size, and higher grading than patients with IDC. Furthermore, luminal molecular subtypes were more represented in ILCs than IDCs, in contrast to HER2-enriched and Triple Negative subtypes, which were lower in ILCs than DCIs. These data align with those reported in the literature on the characteristics of the ILC ( 17 – 19 ). Regarding the number of SLNs removed and the number of metastatic SLNs, although higher in ILC, no significant difference was found between the two groups of patients. This is also consistent with the results of previous studies ( 17 ). However, among patients with macro-metastases in the SLN, those with ILC more frequently had metastases to non-SLNs than patients with IDC (66.7% ILC vs 45% IDC p = 0.02). The multivariate analysis highlighted that ILC is the most influential factor in predicting the presence of metastases to non-SLNs in patients with macro-metastases in the SLN. This data is comparable to that reported in previous studies, which have demonstrated that the ILC tends to have a more significant number of positive non-sentinel lymph nodes ( 10 , 20 – 23 ). However, the issue remains controversial, given that other authors have reported opposite results, concluding that ILC histology is not associated with a greater risk of metastatic involvement of non-sentinel axillary lymph nodes ( 11 , 24 ). The reason for a greater number of metastatic axillary lymph nodes in the ILC may lie in the loss of function of E-cadherin, a trans-membrane protein, typically absent in the ILC, which forms bonds in the extracellular space that joins the plasma membrane to actin and the microtubule cytoskeleton. Its loss would decrease cohesion between tumor cells, increasing the rate of multiple metastases ( 20 , 22 ). Furthermore, previous studies have demonstrated that ILC infiltration typically lacks desmoplastic reaction and does not destroy anatomical structures. Consequently, nodal metastases in the ILC may be more challenging to detect at diagnosis through imaging and may increase the number of metastases to non-SLNs ( 22 , 25 ). Furthermore, in some studies, it is reported that the false negative rate of ultrasound-guided fine needle biopsies was higher in ILC than in IDC because small, uniform cells without nuclear atypia are found in ILC, and the distinction between tumor cells and histiocytes is difficult. This issue may also underlie the underestimation of nodal status at diagnosis ( 20 , 26 ). Other studies have identified the size of SLNs metastases and extracapsular invasion into the SLN as predictive factors for non-SLNs positivity after SLNB. They also demonstrated that patients with micro-metastases in the SLN have a lower incidence of metastasis to non-SLNs than those with macro-metastases. However, these predictive factors have been determined in patients affected predominantly by IDC and a small percentage of ILC ( 3 , 20 , 21 , 25 , 27 , 28 ). For these reasons, further studies are undoubtedly needed to examine the predictive factors of non-sentinel lymph node positivity in cohorts of ILC patients with macro-metastases in the SLN. In the ASOCOG Z0011 trial, patients randomized to SLNB followed by ALND had a non-SLN positivity rate of 27% ( 4 ). Roberts et al. analyzed the treatment of the axilla in ILC, reporting a positivity of 40% for non-SLNs. However, when ILCs met the ACOSOG Z001 criteria, non-sentinel lymph node positivity dropped to 17%. ( 9 ) Gao et al. found that ILC had similar rates of metastasis to non-SLNs compared to IDC among patients with 1–2 positive SLNs (31.2% in ILC vs. 28.6% in IDC, p = 0.481) ( 11 ). However, there were only 182 patients with IDC and five patients with 1–2 SLN positive ILCs in their study. In contrast, in the AMAROS trial, ILC cases had a rate of metastasis to non-SLNs of 43%, higher than that of all other tumor types ( 29 ). Zhang et al. reported a higher incidence of metastasis in non-SLNs for ILC compared to IDC among patients with 1–2 positive SLNs. However, the difference was insignificant (45.4% in ILC, n = 30 vs. 34, 8% in IDC, n = 1,122, P = 0.366) ( 30 ). Therefore, surgeons should be more cautious in omitting ALND for ILC patients with 1–2 positive SLNs. Furthermore, there needs to be more certain data in the literature on the prognosis of ILC after the omission of ALND. Some studies have shown that overall survival was more significant in ILC than in IDC ( 6 , 17 ). However, numerous other studies have shown that ILC, despite favorable biological characteristics, does not have a better clinical outcome than IDC ( 10 , 17 , 18 ). Furthermore, ILC appears to have a lower response to chemotherapy than IDC ( 7 , 10 ). Although some studies have suggested that radiotherapy after conservative surgery has the same loco-regional control in both ILC and IDC ( 31 ), no study has demonstrated the difference in sensitivity to radiotherapy between ILC and IDC. Therefore, it would be appropriate to include the sensitivity of the ILC to adjuvant therapies in the decision-making process for omitting ALND in patients with 1–2 positive SLNs. 5. Conclusions Our study has some limitations as it is retrospective, includes data from only one institution, and the number of patients with ILC is relatively low compared to that of patients with IDC. However, we would like to conclude that the ILC presents more metastases to non-SLNs than the IDC and that it must be considered an important predictive factor for the positivity of non-SLNs in cases of macro-metastasis to the SLNs. Consequently, omitting ALND in patients with ILC who meet the ASOCOG Z0011 trial criteria may underestimate the number of metastatic axillary lymph nodes, risking less accurate staging and selecting less effective adjuvant therapy. The decision to omit ALND in ILC with positive sentinel lymph nodes requires a more thorough evaluation. Declarations Authors’ contributions C.C. and M.R.V. conceptualization, methodology, data curation, visualization, writing, original draft, and formal analysis; S.L., N.G., G.T., M.G., D.E. data collection, and revision; VG paper writing and revision. All available data are presented in the paper. The authors read and approved the final manuscript. Funding No funding was available for the study. Availability of data and materials The data analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate. Ethics approval was obtained according to the Italian rules for retrospective studies by communication to the Ethics Committee of the University Hospital of Palermo. Competing interests The authors declare no competing interests. Author details 1 Department of Surgical Oncological and Oral Sciences, University of Palermo 2 Breast Unit - AOUP Paolo Giaccone Palermo 3 UOC Medical Oncology - AOUP Paolo Giaccone Palermo 4 Medical Oncology, School of Medicine, University of Enna Kore, Enna, Italy, Director Medical Oncology Unit, Cdc Torina, Palermo, Italy. 5 Co-coordinator scientific research, Humanitas Istituto Clinico Catanese, Misterbianco, Catania, Italy References Krag, D.N., Anderson, S.J., Julian, T.B., Brown, A.M., Harlow. S.P., Costantino, J.P., Ashikaga, T., Weaver, D.L., Mamounas, E.P., Jalovec, L.M., Frazier, T.G., Noyes, R.D., Robidoux, A., Mc Scarth, H., Wolmark, N.. 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Similar long-term results of breast-conservation treatment for Stage I and II invasive lobular carcinoma compared with invasive ductal carcinoma of the breast: the University of Pennsylvania experience. Cancer. 103, 2447–2454 (2005) https://doi.org/10.1002/cncr.21071 Tables Table 1: Clinical and pathological characteristics of patients Characteristic IDC (n. 2018 pts) N (%) ILC (n. 315 pts) N (%) P value Age at diagnosis < 50 ≥ 50 207 (10.3) 1811 (89.7) 8 (2.5) 307 (97.5) <0.01 Pathological tumor size T1 T2 T3 1271 (62.9) 689 (34.1) 58 (2.9) 201 (63.8) 92 (29.2) 22 (6.9) <0.01 Tumor Grade G1 G2 G3 365 (18.1) 1199 (59.4) 454 (22.5) 43 (13.7) 211 (66.9) 61 (19.4) <0.01 Molecular subtype Luminal A Luminal B HER2 enriched TNBC 594 (29.4) 917 (45.4) 263 (13.1) 244 (12.1) 132 (41.9) 152 (48.2) 13 (4.1) 18 (5.7) <0.001 Surgical treatment Breast conservative surgery Total Mastectomy 1427 (70,7) 591 (29.3) 218 (69.2) 97 (30.8) 0.89 Number of resected SLNs Average number Range 3.9 1 - 5 4.2 1 – 7 0.72 Table 2: Number of metastatic non-SLNs, comparison between ILC and IDC Number of metastatic non-SLN IDC 207 SLN+ patients N (%) ILC 78 SLN+ patients N (%) 0 253 (55) 26 (33.3%) 1 97 (21.1) 16 (20.5) 2 31 (6.7) 6 (7.7) 3 18 (3.9) 9 (11.5) 4 or more 61 (13.2) 21 (26.9) Table 3: Multivariate analysis for non-SLN metastases Variables OR 95% CI P value Pathology (ILC/IDC) 2.81 1.09-7.41 0.037 Age (≥50/<50) 0.61 0.32-1.19 0.142 Tumor size T1 T2 T3 0.87 1.74 1.16 0.17-4.91 0.27-11.01 0.14-9.32 0.861 0.521 0.919 Tumor Grade G1 G2 G3 1.00 1.19 0.90 0.65-2.19 0.43-1.88 Molecular subtype Luminal A Luminal B HER2 enriched TNBC 1.47 1.22 1.74 1.78 0.77-2.79 0.98-2.42 0.93-2.94 0.82-2.99 0.232 0.751 0.813 0.643 Number of positive SLN (≥3 / ≤2) 4.97 1.65-1 0.005 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 17 Feb, 2024 Reviews received at journal 27 Jan, 2024 Reviewers agreed at journal 27 Jan, 2024 Reviewers invited by journal 26 Jan, 2024 Editor assigned by journal 23 Jan, 2024 Submission checks completed at journal 16 Jan, 2024 First submitted to journal 13 Jan, 2024 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-3860683","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":267510753,"identity":"953993a0-3f87-4940-9fa6-6477aeec2a76","order_by":0,"name":"Calogero Cipolla","email":"","orcid":"","institution":"University of Palermo","correspondingAuthor":false,"prefix":"","firstName":"Calogero","middleName":"","lastName":"Cipolla","suffix":""},{"id":267510754,"identity":"e3e055d8-82df-41ca-9536-631b350a8c6c","order_by":1,"name":"Simona Lupo","email":"","orcid":"","institution":"University of Palermo","correspondingAuthor":false,"prefix":"","firstName":"Simona","middleName":"","lastName":"Lupo","suffix":""},{"id":267510755,"identity":"3e376a42-3ceb-4173-ab3e-39aed678d7e0","order_by":2,"name":"Nello Grassi","email":"","orcid":"","institution":"University of Palermo","correspondingAuthor":false,"prefix":"","firstName":"Nello","middleName":"","lastName":"Grassi","suffix":""},{"id":267510756,"identity":"c15b94db-09e5-41a1-8170-d5f61e7be277","order_by":3,"name":"Giuseppe Tutino","email":"","orcid":"","institution":"University of Palermo","correspondingAuthor":false,"prefix":"","firstName":"Giuseppe","middleName":"","lastName":"Tutino","suffix":""},{"id":267510757,"identity":"de804e7c-40c2-48c0-babd-9d0e78fe5a2d","order_by":4,"name":"Martina Greco","email":"","orcid":"","institution":"University of Palermo","correspondingAuthor":false,"prefix":"","firstName":"Martina","middleName":"","lastName":"Greco","suffix":""},{"id":267510758,"identity":"2ddf5ef0-7ea6-4731-82fa-3d28c366568d","order_by":5,"name":"D’Agati Eleonora","email":"","orcid":"","institution":"University of Palermo","correspondingAuthor":false,"prefix":"","firstName":"D’Agati","middleName":"","lastName":"Eleonora","suffix":""},{"id":267510759,"identity":"faf5ec3f-8e5b-44f2-8f1d-131974b591eb","order_by":6,"name":"Vittorio Gebbia","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCklEQVRIie3PsUrEMBjA8a8EMoXL+h0H7SukFNRB7lmuFOx00F3QSlYfIDf7An2AG3IErsuB64EOB4XOvcVJ0LZ6KtKcjoL5DxlCfvkSAJfrL0b6FbuFEhDgA3iy36NWQrz8K4k+id10BN4JQJwfJtvGiJKXu/3yzAd+t66ybJoWD1KK/fIcRkE+TAzxblSNEWCdRkok8+JxJWNVX1gfNpbEk0xjnOPmZMIEmRfbWBqmzW/I/VNLrlPxRl6shJMD4be0JWbWkYRpfYyEC6UxokhP27+U4aIlodIJo3Q2SChf7ZpGX/mcm7rKni+D0TatsNFTP5B6eMyHxW93suPn+yf+cKfL5XL9314B009UPaJmLhEAAAAASUVORK5CYII=","orcid":"","institution":"University of Enna Kore","correspondingAuthor":true,"prefix":"","firstName":"Vittorio","middleName":"","lastName":"Gebbia","suffix":""},{"id":267510760,"identity":"f66aef96-c2e0-4c24-978e-e0d7ac036090","order_by":7,"name":"Maria Rosaria Valerio","email":"","orcid":"","institution":"University of Palermo","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"Rosaria","lastName":"Valerio","suffix":""}],"badges":[],"createdAt":"2024-01-13 16:29:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3860683/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3860683/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49825218,"identity":"7724eaae-df2f-4ab3-92b0-c9519fb38e0d","added_by":"auto","created_at":"2024-01-18 15:43:27","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":237138,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStudy flow chart\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3860683/v1/0689c95b8507ebc08a01c44e.jpeg"},{"id":49826446,"identity":"f96a5624-350b-41a9-8777-baa80b9551a3","added_by":"auto","created_at":"2024-01-18 15:51:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":387524,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3860683/v1/973474e7-6a9b-460f-b8e3-e9775ecfe00a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Correlation between sentinel lymph node biopsy and non-sentinel lymph node metastasis in patients with cN0 breast carcinoma: comparison of invasive ductal carcinoma and invasive lobular carcinoma","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eSentinel lymph node biopsy (SLNB) has now been confirmed as a standard surgical procedure for staging the axilla in patients with early breast cancer (BC) and clinically negative lymph nodes (cN0), limiting the use of axillary lymph node dissection (ALND) to patients with positive SLNs (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). However, positivity in non-SLNs is only found in approximately 34\u0026ndash;50% of patients with positive SLNs undergoing completion of ALND (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The ACOSOG Z0011 study demonstrated that omitting ALND in cT1-2 cN0 cM0 patients with 1\u0026ndash;2 positive SLNs resulted in a non-inferior outcome compared to patients undergoing ALND (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). However, patients with invasive ductal carcinoma (IDC) constitute more than 80% of the ACOSOG Z0011 study population. For this reason, some questions have been raised about applying its findings to other histological types, particularly invasive lobular carcinoma (ILC).\u003c/p\u003e \u003cp\u003eAlthough ILC represents only approximately 5\u0026ndash;10% of all BC, its immunophenotypic characteristics, clinical course, and therapy response present unique aspects that require particular attention. ILC more frequently shows positivity for hormone receptors and little or no expression for human epidermal growth factor receptor-2 (HER2) compared to IDC. The response to chemotherapy is significantly lower than that of IDC (\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRecent studies have shown that ILC has a similar rate of metastasis to non-SLNs compared to IDC, thus supporting the idea that applying the ACOSOG Z0011 criteria is safe even in patients with ILC (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). However, information regarding the implementation of SLNB in ​​patients with ILC is still scarce, and the question remains unclear whether patients with ILC and 1\u0026ndash;2 positive SLNs can be exempted from ALND (\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) without effects on survival.\u003c/p\u003e \u003cp\u003eIn this study, we retrospectively compared the rates of metastatic lymph node involvement in non-SLNs between patients with IDC and those with ILC, intending to offer a further contribution to the question of whether the ACOSOG Z0011 trial criteria can also be safely applied to patients with ILC.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cp\u003e \u003cb\u003eStudy design\u003c/b\u003e \u003c/p\u003e \u003cp\u003e After approval by the Institutional Review Board of the University Hospital AUOP Paolo Giaccone of Palermo, we collected and retrospectively analyzed the clinical records of an extensive series of patients with cN0 primary invasive BC observed at our institution between 2012 and 2023. The aim of this retrospective study was to compare the rates of metastatic lymph node involvement in non-SLNs between patients with IDC and those with ILC to confirm of the ACOSOG Z0011 trial criteria can also be safely applied to patients with ILC.\u003c/p\u003e \u003cp\u003e \u003cb\u003eInclusion and exclusion criteria.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eData relating to patients with IDC and ILC who underwent SLNB were included in the study.\u003c/p\u003e \u003cp\u003eExclusion criteria from the study were previous neoadjuvant therapy, inflammatory BC, locally recurrent BC, metastatic disease at the diagnosis, and lack of complete data. In all cases, the diagnosis of BC was made using a percutaneous biopsy with a 14G tru-cut needle or a vacuum-assisted breast biopsy with a 7G cannula (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Histopathological diagnoses of ILC and IDC were made with hematoxylin-eosin staining. Furthermore, the expressivity of the hormone receptors for estrogen and progesterone and HER-2 and the Ki-67 cell proliferation index were evaluated. Tumors were then classified based on molecular subtypes. The diagnosis of IDC was confirmed by positive immunohistochemical staining for E-cadherin. Clinical evaluation of the axilla was performed with clinical examination, ultrasound, and cytological examination using FNAC of the suspicious lymph nodes. Women with clinically negative axillary lymph nodes underwent SLNB. The SLN was detected using the radiotracer identification technique and, if necessary, using vital dye, as described in our previous studies (\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). All patients underwent synchronous breast cancer excision by breast-conserving surgery or total mastectomy and SLNB. The recovered SLNs were analyzed during surgery using frozen section (FS) histological examination. All SLNs were subsequently examined with definitive histopathological examination complete with immunohistochemistry (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). In cases where suspicious non-SLNs were present on intraoperative palpation of the axilla, these were removed at the same time as the SLNB and sent separately to the FS for histological examination. ALND was not performed in patients with negative SLN, isolated tumor cells (ITC), or micrometastases. In the case of macrometastases at FS in the SLN or in any non-SLN removed simultaneously, the patients immediately underwent completion ALND. In cases of SLN or non-SLNs negative at FS but positive for macrometastases at the definitive histopathological examination, ALND was completed in a second operation.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eDifferences between the two patient cohorts were calculated using the χ2 test. The statistical significance limit was defined as a p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05. A logistic regression analysis was performed to examine the factors that influenced the presence of metastases to non-SLNs when the SLN had macro-metastases.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eThe clinical records of 2583 patients with infiltrating BC operated between 2012 and 2023 were evaluated: 2242 (86.8%) with IDC and 341 (13.2%) with ILC. Two hundred twenty-four patients with IDC and 26 patients with ILC were excluded from the study as they initially underwent ALND. Ultimately, 2333 patients were included in the study, of which 2018 (86.4%) had IDC and 315 (13.5%) had ILC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients\u0026rsquo; population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe clinical and pathological characteristics of the two cohorts of patients are summarized in Table 1. Patients with ILC were older at diagnosis than those with IDC (p \u0026lt; 0.01). The Luminal A molecular subtype was the most represented in ILC compared to IDC, unlike the HER2-enriched and Triple Negative subtypes, which were lower in ILC than DCI (p \u0026lt; 0.001). Furthermore, ILCs were found to have a larger diameter (p\u0026lt;0.01) and a higher histological grade (p\u0026lt;0.01) compared to IDCs.\u003c/p\u003e\n\u003cp\u003eThe presence of metastases in the SLN was found in 93 patients (29.5%) with ILC; 15 cases were excluded as they were micrometastases, and in the end, a macrometastases was found in 78 of the 315 patients (24.8%) with ILC. The presence of metastases in the SLN was found in 607 patients (30%) with IDC; 147 cases were excluded as they were micrometastases, and ultimately, a macrometastases was found in 460 of the 2018 patients (22.8%) with ILC. The difference between the two groups was not significant (p 0.31).\u003c/p\u003e\n\u003cp\u003eMetastases to non-SLNs were found in 52/78 patients (66.7%) with ILC and in 207/460 patients (45%) with positive SLNs and undergoing completion ALND, with a statistically significant difference between the two groups (p = 0.02). The data are summarized in Figure 1. Furthermore, as can be seen in Table 2, the number of metastatic non-SLNs was more significant in ILC compared to IDC.\u003c/p\u003e\n\u003cp\u003eThe multivariate analysis also showed that in patients with macrometastases in the SLN, in addition to the number of positive SLNs, the ILC histotype represents the most influential factor in predicting the presence of metastases in non-SLNs concerning age, tumor size, grade histological and molecular subtype (Table 3).\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn our study, patients with ILC had a higher mean age, larger tumor size, and higher grading than patients with IDC. Furthermore, luminal molecular subtypes were more represented in ILCs than IDCs, in contrast to HER2-enriched and Triple Negative subtypes, which were lower in ILCs than DCIs. These data align with those reported in the literature on the characteristics of the ILC (\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Regarding the number of SLNs removed and the number of metastatic SLNs, although higher in ILC, no significant difference was found between the two groups of patients. This is also consistent with the results of previous studies (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, among patients with macro-metastases in the SLN, those with ILC more frequently had metastases to non-SLNs than patients with IDC (66.7% ILC vs 45% IDC p\u0026thinsp;=\u0026thinsp;0.02). The multivariate analysis highlighted that ILC is the most influential factor in predicting the presence of metastases to non-SLNs in patients with macro-metastases in the SLN. This data is comparable to that reported in previous studies, which have demonstrated that the ILC tends to have a more significant number of positive non-sentinel lymph nodes (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). However, the issue remains controversial, given that other authors have reported opposite results, concluding that ILC histology is not associated with a greater risk of metastatic involvement of non-sentinel axillary lymph nodes (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe reason for a greater number of metastatic axillary lymph nodes in the ILC may lie in the loss of function of E-cadherin, a trans-membrane protein, typically absent in the ILC, which forms bonds in the extracellular space that joins the plasma membrane to actin and the microtubule cytoskeleton. Its loss would decrease cohesion between tumor cells, increasing the rate of multiple metastases (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Furthermore, previous studies have demonstrated that ILC infiltration typically lacks desmoplastic reaction and does not destroy anatomical structures. Consequently, nodal metastases in the ILC may be more challenging to detect at diagnosis through imaging and may increase the number of metastases to non-SLNs (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Furthermore, in some studies, it is reported that the false negative rate of ultrasound-guided fine needle biopsies was higher in ILC than in IDC because small, uniform cells without nuclear atypia are found in ILC, and the distinction between tumor cells and histiocytes is difficult. This issue may also underlie the underestimation of nodal status at diagnosis (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOther studies have identified the size of SLNs metastases and extracapsular invasion into the SLN as predictive factors for non-SLNs positivity after SLNB. They also demonstrated that patients with micro-metastases in the SLN have a lower incidence of metastasis to non-SLNs than those with macro-metastases. However, these predictive factors have been determined in patients affected predominantly by IDC and a small percentage of ILC (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). For these reasons, further studies are undoubtedly needed to examine the predictive factors of non-sentinel lymph node positivity in cohorts of ILC patients with macro-metastases in the SLN.\u003c/p\u003e \u003cp\u003eIn the ASOCOG Z0011 trial, patients randomized to SLNB followed by ALND had a non-SLN positivity rate of 27% (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Roberts et al. analyzed the treatment of the axilla in ILC, reporting a positivity of 40% for non-SLNs. However, when ILCs met the ACOSOG Z001 criteria, non-sentinel lymph node positivity dropped to 17%. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) Gao et al. found that ILC had similar rates of metastasis to non-SLNs compared to IDC among patients with 1\u0026ndash;2 positive SLNs (31.2% in ILC vs. 28.6% in IDC, p\u0026thinsp;=\u0026thinsp;0.481) (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). However, there were only 182 patients with IDC and five patients with 1\u0026ndash;2 SLN positive ILCs in their study. In contrast, in the AMAROS trial, ILC cases had a rate of metastasis to non-SLNs of 43%, higher than that of all other tumor types (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Zhang et al. reported a higher incidence of metastasis in non-SLNs for ILC compared to IDC among patients with 1\u0026ndash;2 positive SLNs. However, the difference was insignificant (45.4% in ILC, n\u0026thinsp;=\u0026thinsp;30 vs. 34, 8% in IDC, n\u0026thinsp;=\u0026thinsp;1,122, P\u0026thinsp;=\u0026thinsp;0.366) (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Therefore, surgeons should be more cautious in omitting ALND for ILC patients with 1\u0026ndash;2 positive SLNs.\u003c/p\u003e \u003cp\u003eFurthermore, there needs to be more certain data in the literature on the prognosis of ILC after the omission of ALND. Some studies have shown that overall survival was more significant in ILC than in IDC (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). However, numerous other studies have shown that ILC, despite favorable biological characteristics, does not have a better clinical outcome than IDC (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurthermore, ILC appears to have a lower response to chemotherapy than IDC (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Although some studies have suggested that radiotherapy after conservative surgery has the same loco-regional control in both ILC and IDC (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), no study has demonstrated the difference in sensitivity to radiotherapy between ILC and IDC. Therefore, it would be appropriate to include the sensitivity of the ILC to adjuvant therapies in the decision-making process for omitting ALND in patients with 1\u0026ndash;2 positive SLNs.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eOur study has some limitations as it is retrospective, includes data from only one institution, and the number of patients with ILC is relatively low compared to that of patients with IDC. However, we would like to conclude that the ILC presents more metastases to non-SLNs than the IDC and that it must be considered an important predictive factor for the positivity of non-SLNs in cases of macro-metastasis to the SLNs. Consequently, omitting ALND in patients with ILC who meet the ASOCOG Z0011 trial criteria may underestimate the number of metastatic axillary lymph nodes, risking less accurate staging and selecting less effective adjuvant therapy. The decision to omit ALND in ILC with positive sentinel lymph nodes requires a more thorough evaluation.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eC.C. and M.R.V. conceptualization, methodology, data curation, visualization, writing, original draft, and formal analysis; S.L., N.G., G.T., M.G., D.E. data collection, and revision; VG paper writing and revision. All available data are presented in the paper. The authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was available for the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data analyzed during the current study are available from the corresponding author on reasonable request. \u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate. \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval was obtained according to the Italian rules for retrospective studies by communication to the Ethics Committee of the University Hospital of Palermo. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003e Department of Surgical Oncological and Oral Sciences, University of Palermo\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003e Breast Unit - AOUP Paolo Giaccone Palermo\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e3\u003c/sup\u003e UOC Medical Oncology - AOUP Paolo Giaccone Palermo\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e4\u003c/sup\u003e Medical Oncology, School of Medicine, University of Enna Kore, Enna, Italy, Director Medical Oncology Unit, Cdc Torina, Palermo, Italy. \u003c/p\u003e\n\u003cp\u003e\u003csup\u003e5\u003c/sup\u003eCo-coordinator scientific research, Humanitas Istituto Clinico Catanese, Misterbianco, Catania, Italy\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKrag, D.N., Anderson, S.J., Julian, T.B., Brown, A.M., Harlow. 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Surg. 182, 316\u0026ndash;320 (2001) \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/s0002-9610(01)00719-x\u003c/span\u003e\u003cspan address=\"10.1016/s0002-9610(01)00719-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDonker, M., van Tienhoven, G., Straver, M. E., Meijnen, P., van de Velde, C. J., Mansel, R. E., Cataliotti, L., Westenberg, A. H., Klinkenbijl, J. H., Orzalesi, L., Bouma, W. H., van der Mijle, H. C., Nieuwenhuijzen, G. A., Veltkamp, S. C., Slaets, L., Duez, N. J., de Graaf, P. W., van Dalen, T., Marinelli, A., Rijna, H., Snoj, M., Bundred, N.J., Merkus, J.W., Belkacemi, Y., Petignat, P., Schinagl, D.A., Coens, C., Messina, C.G., Bogaerts, J., Rutgers, E.J. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981\u0026ndash;22023 AMAROS): a randomised, multicentre, open-label, phase 3 noninferiority trial. Lancet Oncol. 15, 1303\u0026ndash;1310 (2014) \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S1470-2045(14)70460-7\u003c/span\u003e\u003cspan address=\"10.1016/S1470-2045(14)70460-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang, J., Ling, Y., Wang, T., Yan, C., Huang, M., Fan, Z., Ling, R. Chinese Society of Breast Cancer. Analysis of sentinel lymph node biopsy and non-sentinel lymph node metastasis in invasive ductal and invasive lobular breast cancer: a nationwide cross-sectional study (CSBrS-001). Ann. Transl. Med. 9(20), 1588 (2021) \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.21037/atm-21-5169\u003c/span\u003e\u003cspan address=\"10.21037/atm-21-5169\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSantiago, R.J., Harris, E.E., Qin, L., Hwang, W.T., Solin, L.J. Similar long-term results of breast-conservation treatment for Stage I and II invasive lobular carcinoma compared with invasive ductal carcinoma of the breast: the University of Pennsylvania experience. Cancer. 103, 2447\u0026ndash;2454 (2005) \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/cncr.21071\u003c/span\u003e\u003cspan address=\"10.1002/cncr.21071\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1: Clinical and pathological characteristics of patients\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.274647887323944%\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.345070422535212%\"\u003e\n \u003cp\u003eIDC (n. 2018 pts)\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003eILC (n. 315 pts)\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.380281690140846%\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.274647887323944%\"\u003e\n \u003cp\u003e\u003cu\u003eAge at diagnosis\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt; 50\u003c/p\u003e\n \u003cp\u003e\u0026ge; 50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.345070422535212%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e207 (10.3)\u003c/p\u003e\n \u003cp\u003e1811 (89.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (2.5)\u003c/p\u003e\n \u003cp\u003e307 (97.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.380281690140846%\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.274647887323944%\"\u003e\n \u003cp\u003e\u003cu\u003ePathological tumor size\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.345070422535212%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1271 (62.9)\u003c/p\u003e\n \u003cp\u003e689 (34.1)\u003c/p\u003e\n \u003cp\u003e58 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e201 (63.8)\u003c/p\u003e\n \u003cp\u003e92 (29.2)\u003c/p\u003e\n \u003cp\u003e22 (6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.380281690140846%\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.274647887323944%\"\u003e\n \u003cp\u003e\u003cu\u003eTumor Grade\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003eG1\u003c/p\u003e\n \u003cp\u003eG2\u003c/p\u003e\n \u003cp\u003eG3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.345070422535212%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e365 (18.1)\u003c/p\u003e\n \u003cp\u003e1199 (59.4)\u003c/p\u003e\n \u003cp\u003e454 (22.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e43 (13.7)\u003c/p\u003e\n \u003cp\u003e211 (66.9)\u003c/p\u003e\n \u003cp\u003e61 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.380281690140846%\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.274647887323944%\"\u003e\n \u003cp\u003e\u003cu\u003eMolecular subtype\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003eLuminal A\u003c/p\u003e\n \u003cp\u003eLuminal B\u003c/p\u003e\n \u003cp\u003eHER2 enriched\u003c/p\u003e\n \u003cp\u003eTNBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.345070422535212%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e594 (29.4)\u003c/p\u003e\n \u003cp\u003e917 (45.4)\u003c/p\u003e\n \u003cp\u003e263 (13.1)\u003c/p\u003e\n \u003cp\u003e244 (12.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e132 (41.9)\u003c/p\u003e\n \u003cp\u003e152 (48.2)\u003c/p\u003e\n \u003cp\u003e13 (4.1)\u003c/p\u003e\n \u003cp\u003e18 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.380281690140846%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.274647887323944%\"\u003e\n \u003cp\u003e\u003cu\u003eSurgical treatment\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003eBreast conservative surgery\u003c/p\u003e\n \u003cp\u003eTotal Mastectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.345070422535212%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1427 (70,7)\u003c/p\u003e\n \u003cp\u003e591 (29.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e218 (69.2)\u003c/p\u003e\n \u003cp\u003e97 (30.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.380281690140846%\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.274647887323944%\"\u003e\n \u003cp\u003e\u003cu\u003eNumber of resected SLNs\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003eAverage number\u003c/p\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.345070422535212%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.9\u003c/p\u003e\n \u003cp\u003e1 - 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4.2\u003c/p\u003e\n \u003cp\u003e1 \u0026ndash; 7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.380281690140846%\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Number of metastatic non-SLNs, comparison between ILC and IDC\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.275862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eNumber of metastatic non-SLN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.01149425287356%\" valign=\"top\"\u003e\n \u003cp\u003eIDC\u003c/p\u003e\n \u003cp\u003e207 SLN+ patients\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.71264367816092%\" valign=\"top\"\u003e\n \u003cp\u003eILC\u003c/p\u003e\n \u003cp\u003e78 SLN+ patients\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.275862068965516%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.01149425287356%\" valign=\"top\"\u003e\n \u003cp\u003e253 (55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.71264367816092%\" valign=\"top\"\u003e\n \u003cp\u003e26 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.275862068965516%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.01149425287356%\" valign=\"top\"\u003e\n \u003cp\u003e97 (21.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.71264367816092%\" valign=\"top\"\u003e\n \u003cp\u003e16 (20.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.275862068965516%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.01149425287356%\" valign=\"top\"\u003e\n \u003cp\u003e31 (6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.71264367816092%\" valign=\"top\"\u003e\n \u003cp\u003e6 (7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.275862068965516%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.01149425287356%\" valign=\"top\"\u003e\n \u003cp\u003e18 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.71264367816092%\" valign=\"top\"\u003e\n \u003cp\u003e9 (11.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.275862068965516%\" valign=\"top\"\u003e\n \u003cp\u003e4 or more\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.01149425287356%\" valign=\"top\"\u003e\n \u003cp\u003e61 (13.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.71264367816092%\" valign=\"top\"\u003e\n \u003cp\u003e21 (26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Multivariate analysis for non-SLN metastases\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.92063492063492%\" valign=\"top\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.395061728395063%\" valign=\"top\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\" valign=\"top\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\" valign=\"top\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.92063492063492%\"\u003e\n \u003cp\u003ePathology (ILC/IDC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.395061728395063%\"\u003e\n \u003cp\u003e2.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\"\u003e\n \u003cp\u003e1.09-7.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e0.037\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.92063492063492%\"\u003e\n \u003cp\u003eAge (\u0026ge;50/\u0026lt;50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.395061728395063%\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\"\u003e\n \u003cp\u003e0.32-1.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.142\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.92063492063492%\"\u003e\n \u003cp\u003e\u003cu\u003eTumor size\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.395061728395063%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003cp\u003e1.74\u003c/p\u003e\n \u003cp\u003e1.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.17-4.91\u003c/p\u003e\n \u003cp\u003e0.27-11.01\u003c/p\u003e\n \u003cp\u003e0.14-9.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.861\u003c/p\u003e\n \u003cp\u003e0.521\u003c/p\u003e\n \u003cp\u003e0.919\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.92063492063492%\"\u003e\n \u003cp\u003e\u003cu\u003eTumor Grade\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003eG1\u003c/p\u003e\n \u003cp\u003eG2\u003c/p\u003e\n \u003cp\u003eG3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.395061728395063%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003cp\u003e1.19\u003c/p\u003e\n \u003cp\u003e0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.65-2.19\u003c/p\u003e\n \u003cp\u003e0.43-1.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.92063492063492%\"\u003e\n \u003cp\u003e\u003cu\u003eMolecular subtype\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003eLuminal A\u003c/p\u003e\n \u003cp\u003eLuminal B\u003c/p\u003e\n \u003cp\u003eHER2 enriched\u003c/p\u003e\n \u003cp\u003eTNBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.395061728395063%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.47\u003c/p\u003e\n \u003cp\u003e1.22\u003c/p\u003e\n \u003cp\u003e1.74\u003c/p\u003e\n \u003cp\u003e1.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.77-2.79\u003c/p\u003e\n \u003cp\u003e0.98-2.42\u003c/p\u003e\n \u003cp\u003e0.93-2.94\u003c/p\u003e\n \u003cp\u003e0.82-2.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.232\u003c/p\u003e\n \u003cp\u003e0.751\u003c/p\u003e\n \u003cp\u003e0.813\u003c/p\u003e\n \u003cp\u003e0.643\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.92063492063492%\"\u003e\n \u003cp\u003eNumber of positive SLN (\u0026ge;3 / \u0026le;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.395061728395063%\"\u003e\n \u003cp\u003e4.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\"\u003e\n \u003cp\u003e1.65-1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\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":"world-journal-of-surgical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjso","sideBox":"Learn more about [World Journal of Surgical Oncology](http://wjso.biomedcentral.com)","snPcode":"12957","submissionUrl":"https://submission.nature.com/new-submission/12957/3","title":"World Journal of Surgical Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Breast carcinoma, infiltrating lobular carcinoma, Infiltrating ductal carcinoma, Sentinel lymph node biopsy, Nonsentinel lymph node metastasis, Axillary lymphadenectomy","lastPublishedDoi":"10.21203/rs.3.rs-3860683/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3860683/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Recent studies have suggested that axillary lymph node dissection (ALND) can be avoided in women with cN0 breast cancer with 1-2 positive sentinel nodes (SLNs). However, these studies included only a few patients with invasive lobular carcinoma (ILC), so the validity of omitting ALDN in these patients remains controversial. This study compared the frequency of non-sentinel lymph nodes (non-SLNs) metastases in ILC and invasive ductal carcinoma (IDC). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials Methods: \u003c/strong\u003eData relating to a total of 2583 patients with infiltrating breast carcinoma operated at our institution between 2012 and 2023 were retrospectively analyzed: 2242 (86.8%) with IDC and 341 (13.2%) with ILC. We compared the incidence of metastasis to SLNs and non-SLNs between the ILC and IDC cohorts and examined factors that influenced non-SLNs metastasis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: SLN biopsies were performed in 315 patients with ILC and 2018 patients with IDC. Metastases to the SLNs were found in 78/315 (24.8%) patients with ILC and in 460 (22.8%) patients with IDC (p= 0.31). The incidence of metastases to non-SLNs was significantly higher (p = 0.02) in ILC (52/78 - 66.7%) compared to IDC (207/460 - 45%). Multivariate analysis showed that ILC was the most influential predictive factor in predicting the presence of metastasis to non-SLNs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: ILC cases have more non-SLNs metastases than IDC cases in SLN-positive patients. The ILC is essential for predicting non-SLN positivity in macro-metastases in the SLN. The option of omitting ALND in patients with ILC with 1-2 positive SLNs still requires further investigation.\u003c/p\u003e","manuscriptTitle":"Correlation between sentinel lymph node biopsy and non-sentinel lymph node metastasis in patients with cN0 breast carcinoma: comparison of invasive ductal carcinoma and invasive lobular carcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-18 15:43:22","doi":"10.21203/rs.3.rs-3860683/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-02-17T07:48:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-01-27T15:19:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"2d74b08b-e137-4b26-88fd-a441b180dcc9","date":"2024-01-27T05:19:01+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-01-27T04:58:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-23T15:32:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-01-16T23:32:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"World Journal of Surgical Oncology","date":"2024-01-13T16:17:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-surgical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjso","sideBox":"Learn more about [World Journal of Surgical Oncology](http://wjso.biomedcentral.com)","snPcode":"12957","submissionUrl":"https://submission.nature.com/new-submission/12957/3","title":"World Journal of Surgical Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3fc38e5c-7f51-407c-a7e9-0748b9596f55","owner":[],"postedDate":"January 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-03-29T00:00:44+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-18 15:43:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3860683","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3860683","identity":"rs-3860683","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}