Sentinel lymph node biopsy without frozen section in mastectomy patients: A 5-year survival analysis from King Chulalongkorn Memorial Hospital

Sentinel lymph node biopsy without frozen section in mastectomy patients: A 5-year survival analysis from King Chulalongkorn Memorial Hospital | 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 Sentinel lymph node biopsy without frozen section in mastectomy patients: A 5-year survival analysis from King Chulalongkorn Memorial Hospital Nattanan Treeratanapun, Voranaddha Vacharathit, Kasaya Tantiphlachiva, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8959199/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background Intraoperative frozen section (FS) during sentinel lymph node biopsy (SLNB) has traditionally been used to facilitate immediate axillary lymph node dissection (ALND). However, contemporary axillary de-escalation strategies supported by AMAROS and SENOMAC trials have narrowed indications for ALND, raising questions about the clinical value of routine FS, particularly in mastectomy patients. Methods We retrospectively analyzed early-stage breast cancer patients (T1–T2, clinically node-negative) who underwent mastectomy with SLNB at a single institution between 2017 and 2022. Patients were managed with either intraoperative FS or permanent section (PS) alone. The primary endpoint was 5-year disease-free survival (DFS) using a noninferiority design. Secondary endpoints included overall survival (OS) and patterns of recurrence. Results Among 265 patients, 202 underwent SLNB with FS and 63 with PS alone. Median follow-up was 5.7 and 4.8 years, respectively. Five-year DFS was 92.1% in the FS group and 93.7% in the PS group. The PS strategy was noninferior to FS (hazard ratio [HR], 0.96; 95% CI, 0.28–3.35; noninferiority P = 0.952). Overall survival was comparable (HR, 1.09; 95% CI, 0.13–9.17). Rates of local, regional, and distant recurrence did not differ significantly. Only one patient in the PS group required delayed ALND. Conclusions Omission of intraoperative FS during SLNB in mastectomy patients did not compromise long-term oncologic outcomes. A PS-only strategy appears safe and supports further axillary de-escalation in contemporary practice. Permanent section (PS) Frozen section (FS) Early-stage breast cancer Sentinel lymph node biopsy (SLNB) Figures Figure 1 Figure 2 Introduction SLNB has become the standard technique for axillary staging in clinically node-negative breast cancer, offering equivalent prognostic information to ALND with significantly less morbidity (1) . Traditionally, FS analysis has been employed during SLNB to identify nodal metastases intraoperatively, allowing immediate ALND when necessary and minimizing the need for reoperation (2) . However, this practice has been increasingly challenged by evidence suggesting limited clinical benefit from routine FS. The AMAROS trial and SENOMAC trial has incorporated treatment algorithms in which ALND was generally reserved for patients with a higher axillary nodal burden, typically defined as involvement of more than two sentinel lymph nodes (3, 4) . This paradigm has important implications for the role of FS analysis of sentinel lymph nodes. Because ALND would only be indicated when three or more sentinel lymph nodes are positive, FS would need to reliably identify multiple involved nodes during surgery to meaningfully alter immediate surgical management. Therefore, in the context of modern axillary de-escalation strategies supported by AMAROS and SENOMAC, routine FS offers limited incremental clinical benefit for mastectomy patients. Its continued use may increase operative time, resource utilization, and healthcare costs without translating into improved survival outcomes. Intraoperative FS has demonstrated inconsistent sensitivity particularly for micrometastases and false-negative rates ranging from 10% to 30% (5, 6) . Recent meta-analyses have questioned its necessity, especially in light of evolving guidelines that favor SLNB-only strategies for selected node-positive patients (6, 7) . Moreover, concerns have been raised about discordance between FS and final pathology results, further limiting FS’s impact on clinical decision-making (8) . Our prior retrospective study from King Chulalongkorn Memorial Hospital examined the clinical value of FS during SLNB in patients with early-stage breast cancer undergoing mastectomy (9) . This study showed that omission of FS did not lead to higher reoperation rates or worse short-term outcomes, and that most patients with positive sentinel lymph nodes did not require additional axillary treatment when managed according to the SENOMAC trial criteria (4) . Nevertheless, the scope of those analyses was confined to perioperative and short-term clinical endpoints, leaving long-term oncologic outcomes unaddressed. The current study extends this work by providing a 5-year follow-up of the same patient cohort treated with SLNB with or without intraoperative FS during mastectomy. Its objective is to evaluate disease-free survival and overall survival, and to determine whether omission of intraoperative FS affects long-term oncologic safety in this clinical context. Materials and Methods This retrospective study explored the five-year survival outcomes of early-stage breast cancer patients after being treated with different SLNB techniques. The primary focus was comparing the DFS between the FS and PS groups. Overall survival, recurrence at local and regional levels, and distant metastases, were also reported as secondary outcomes. We included all patients who had undergone SLNB procedure at KCMH from December 2017 to December 2022, with follow-up ending on December 15, 2025. The inclusion criteria were patients with early-stage breast cancer (T1 or T2) with clinically node-negative status and had undergone mastectomy and SLNB. Patients who had received neoadjuvant chemotherapy and non-invasive breast cancer patients were included. A total of 265 SLNB cases were included, in which 63 patients had undergone SLNB using PS alone and 202 patients undergone the FS technique (Fig. 1 ). Demographic, clinical, pathological, and treatment-related data including age, type of breast surgery, final histopathologic diagnosis, pathologic tumor stage (AJCC staging system), Nottingham histologic grade, presence of lymphovascular invasion, estrogen receptor, progesterone receptor, and HER2 status, as well as receipt of adjuvant systemic therapy and post mastectomy radiotherapy (PMRT) were extracted from medical records. Clinicopathologic characteristics were compared between patients undergoing SLNB with intraoperative frozen section (FS) and those evaluated by permanent section (PS) alone. Clinical nodal status was assessed by physical examination, and radiologic nodal evaluation was performed using breast ultrasonography with or without mammography, in accordance with standard preoperative staging practices. Sentinel lymph node mapping was performed using isosulfan blue dye as a single-agent tracer, which represents the standard SLNB technique at King Chulalongkorn Memorial Hospital and is widely used in Thailand. Pathologic evaluation of sentinel lymph nodes was performed using serial sectioning with hematoxylin and eosin staining, supplemented by immunohistochemistry when indicated. Written informed consent was waived due to the retrospective nature of the study. Statistical analysis Data extracted from medical records were collected and managed using Microsoft Excel 2019. Statistical analyses were performed with IBM SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA). Categorical variables were summarized as frequencies and percentages and compared using the Pearson chi-square test or Fisher’s exact test, as appropriate. Disease-free survival (DFS) was defined as the interval from the SLNB procedure to the occurrence of any event, including local breast recurrence, ipsilateral axillary recurrence, distant metastasis, or death from any cause. Overall survival (OS) was defined as the time from SLNB to death from any cause. Local recurrence was defined as tumor recurrence within the breast, while regional recurrence referred to ipsilateral axillary events. Survival curves were estimated using the Kaplan–Meier method and compared between the FS and PS groups using the log-rank test. For the primary endpoint of 5-year DFS, a noninferiority margin of 2.5% was prespecified, with 80% power and a one-sided type I error rate of 5%. As a secondary endpoint, cumulative incidences of local, regional, and distant recurrence were reported for both groups. A two-sided p-value < 0.05 was considered statistically significant for all analyses. For patients who experienced death or were lost to follow-up, the time from SLNB to the last known event or follow-up was recorded. Results A total of 265 SLNB procedures met the inclusion criteria and were included in the analysis. FS evaluation was performed in 202 cases, while 63 cases underwent PS evaluation alone. The median follow-up duration was 5.7 years (interquartile range [IQR], 4.8–6.7) in the FS group and 4.8 years (IQR, 3.5–5.8) in the PS group. Patient age ranged from 34 to 86 years, with a mean age of 55.8 years and a median age of 57.0 years. Comparisons of baseline clinicopathological characteristics between the FS and PS groups are summarized in Table 1. Seven histopathological subtypes were identified, including invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), ductal carcinoma in situ with micrometastasis (DCISM), mucinous carcinoma, papillary carcinoma, tubular carcinoma, and mixed invasive carcinoma. IDC was the predominant subtype, accounting for 204 cases (77.0%). Only one patient in the PS group underwent a second operation for completion ALND. HER2 immunohistochemistry status was unavailable in 11 patients due to equivocal results without subsequent fluorescence in situ hybridization testing. Statistically significant differences were observed between the FS and PS groups with respect to tumor size, hormone receptor status, and the use of ALND. Table 1 : Comparison of Tumor Clinicopathology and Radiolographic nodal status between Frozen section and Permanent section group. Overall Frozen section group Permanent section group p-value Age (yr) 55.76 55.69 ± 12.30 55.96 ± 13.29 0.866 Tumor size 0.004 T1 (< 2 cm) 136 96 (47.5%) 43 (68.2%) T2 (2-5 cm) 131 106 (52.5%) 20 (31.8%) Histologic grade 0.567 1 51 41 (20.3%) 9 (14.3%) 2 131 98 (48.5%) 33 (52.4%) 3 85 63 (31.2%) 21 (33.3%) Histopathology 0.092 IDC 204 164 (81.2%) 45 (71.4%) ILC 14 9 (4.4%) 5 (7.9%) DCISM 30 13 (6.4%) 10 (15.9%) Mucinous 7 7 (3.5%) 0 (0%) Papillary 8 5 (2.5%) 3 (4.8%) Tubular 1 1 (0.5%) 0 (0%) Metaplastic 4 3 (1.5%) 0 (0%) Lymphovascular Invasion 0.097 Yes 72 60 (29.7%) 12 (19.0%) No 195 142 (70.3%) 51 (81.0%) Estrogen receptor 0.004 Positive 195 156 (77.2%) 37 (58.7%) Negative 72 46 (22.8%) 26 (41.3%) Progesterone receptor 0.011 Positive 170 138 (68.3%) 32 (50.8%) Negative 97 64 (31.7%) 31 (49.2%) HER-2 0.725 Positive 74 61 (30.1%) 22 (34.9%) Negative 172 133 (65.8%) 38 (60.3%) Unknown 11 8 (4.1%) 3 (4.8%) ALND <0.001 Yes 50 49 (24.2%) 1 (1.6%) No 215 153 (75.8%) 62 (98.4%) Adjuvant Hormonal Treatment 0.068 Yes 178 142 (70.3%) 36 (51.9%) No 87 60 (29.7%) 27 (56.2%) Adjuvant Chemotherapy 0.113 Yes 146 117 (57.9%) 29 (46.0%) No 119 85 (42.1%) 34 (54.0%) Adjuvant Radiotherapy 0.044 Yes 84 57 (28.2%) 27 (42.9%) No 181 145 (71.8%) 36 (57.1%) Targeted therapy 0.413 Yes 41 32 (15.8%) 9 (14.3%) No 224 170 (84.2%) 54 (85.7%) Total 265 202 63 Values are represented as numbers (%) or mean ± standard deviation. IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; DCISM, ductal carcinoma in situ with microinvasion; HER-2, human epidermal growth factor receptor 2 The 5-year DFS rate was 92.1% in the FS group and 93.7% in the PS group, as shown in Fig. 2 A. The PS group was noninferior to the FS group with respect to DFS, with a HR of 0.96 (95% CI, 0.28–3.35) and a noninferiority P-value of 0.952. OS was comparable between groups (HR, 1.09; 95% CI, 0.13–9.17; noninferiority P = 0.937), as illustrated in Fig. 2 B. Five deaths (2.5%) occurred in the FS group, whereas no deaths were observed in the PS group during follow-up. Subgroup analyses according to tumor size, ALND status, and HER2 status showed consistent findings, with no statistically significant associations between these factors and disease recurrence (adjusted HR, 1.34 (95% CI, 0.44–4.26; P = 0.578), 1.13 (95% CI, 0.32–2.99; P = 0.851), and 1.33 (95% CI, 0.44–4.05; P = 0.613), respectively). Cumulative oncologic outcomes at 5 years are presented in Table 2 . In the FS group, three patients (1.5%) experienced local breast recurrence, four patients (2.0%) developed regional (axillary) recurrence, and eight patients (4.0%) developed distant metastases. In the PS group, one patient (1.6%) had a local recurrence, one patient (1.6%) experienced axillary recurrence, and two patients (3.2%) developed distant metastases. No statistically significant differences were observed between groups for any oncologic outcome, as demonstrated in Fig. 2 A–E. Table 2 Summary of 5-year survival outcomes Local recurrences No. of event in FS group No. of event in PS group P- value 3 (1.5%) 1 (1.6%) 0.667 Regional recurrence 4 (2.0%) 1 (1.6%) 0.657 Distant metastases 8 (4.0%) 2 (3.2%) 0.559 Deaths 5 (2.5%) 0 (0.0%) 0.253 Disease-free survival 16 (7.9%) 4 (6.3%) 0.457 Values are represented as number. FS, frozen section; PS, permanent section. Discussion FS of sentinel lymph nodes was historically adopted primarily to avoid a second operation by enabling immediate ALND when nodal metastases were identified intraoperatively (10, 11) . However, the contemporary evidence base has narrowed the indications for ALND after SLNB. In patients undergoing mastectomy who otherwise meet criteria for axillary de-escalation, multiple trials have established that with the post-mastectomy radiotherapy (PMRT), completion ALND can be safely omitted when only one or two sentinel nodes are involved, with no detriment in long-term oncologic outcomes. As a result, the potential benefit of FS is now largely confined to the scenario in which more than two sentinel nodes are positive, because only then would intraoperative identification be expected to alter management by prompting immediate ALND (3, 4) . Moreover, this paradigm has been increasingly questioned in the modern era, as systemic therapy and regional nodal irradiation have reduced the clinical impact of low-volume nodal disease (12, 13) . Consistent with this shift, an expanding body of literature supports that routine intraoperative FS can be omitted in early-stage breast cancer treated with breast-conserving surgery, without a clinically meaningful increase in reoperation rates (14, 15) . More recently, axillary de-escalation has progressed further: randomized evidence demonstrates that omission of SLNB in carefully selected patients undergoing primary breast-conserving surgery (typically clinically node-negative with negative preoperative axillary ultrasound and favorable biology) is noninferior to SLNB for key survival endpoints, supporting “no axillary surgery” approaches in defined low-risk groups (16, 17) . Nevertheless, even in mastectomy populations where surgeons may be more reluctant to de-escalate axillary management, some studies have questioned the routine use of intraoperative FS because it often does not translate into a meaningful reduction in reoperations, particularly as ALND thresholds have become more restrictive and systemic/radiation strategies have evolved (9, 18) . In line with this, our previous institutional work also demonstrated that SLNB performed without intraoperative FS was not inferior in terms of reoperation rates, reinforcing the limited practical benefit of FS in contemporary management and supporting a PS-only strategy in appropriate patients (9) . In this study, omission of FS during mastectomy for early-stage breast cancer did not compromise oncologic outcomes. At 5 years, disease-free survival (DFS) was 92.1% in the FS group and 93.7% in the permanent section (PS) group, with the PS strategy meeting predefined noninferiority criteria (HR, 0.96; 95% CI, 0.28–3.35; P = 0.952). These results indicate that omission of FS does not increase the risk of disease recurrence when treatment decisions are guided by final pathology and contemporary multimodality therapy, consistent with prior institutional and multi-institutional series evaluating FS omission in mastectomy patients (12, 19, 20) . Patterns of recurrence further reinforce the oncologic equivalence of the two approaches. Local recurrence occurred in 1.5% of patients in the FS group and 1.6% in the PS group, while regional (axillary) recurrence rates were 2.0% and 1.6%, respectively. Distant metastases developed in 4.0% of FS patients and 3.2% of PS patients, with no statistically significant differences across any oncologic endpoint. These low recurrence rates are comparable to those reported in modern mastectomy studies and support the safety of delayed axillary management based on permanent pathology (3, 4, 21) . An interesting observation in our cohort was the numerically higher incidence of overall recurrence incidences in the FS group, although these differences were not statistically significant. Notably, rare late overall locoregional and distant metastases occurring beyond eight years in the both groups raise questions regarding the long-term reliability of FS-based decision-making. A similar pattern of late recurrence following SLNB has been reported, underscoring the importance of extended follow-up in de-escalation studies (22) . In one cohort of clinically node-negative patients undergoing upfront mastectomy, omission of FS significantly reduced unnecessary ALND without adversely affecting oncologic outcomes (19, 23) . Contemporary axillary management for patients with early-stage breast cancer undergoing mastectomy and found to have one to two positive sentinel lymph nodes has increasingly shifted toward postmastectomy radiotherapy (PMRT) rather than routine completion ALND (24, 25) . This paradigm change is supported by randomized evidence demonstrating comparable locoregional control between axillary radiotherapy and ALND, as shown in the SENOMAC, AMAROS, and OTOASOR trials (3, 4, 21) . As a result, PMRT has emerged as a preferred strategy in appropriately selected patients, offering effective regional control while reducing treatment-related morbidity associated with more extensive axillary surgery. Looking forward, ongoing prospective trials are expected to further refine axillary treatment by identifying subsets of node-positive patients who may safely avoid both ALND and PMRT. Studies such as POSNOC trial and T-REX trial are evaluating whether carefully selected patients, particularly those with hormone receptor–positive, HER2-negative, biologically low-risk tumors and limited nodal involvement, can achieve excellent oncologic outcomes with SLNB alone (26, 27) . Collectively, these efforts reflect a continued movement toward axillary de-escalation in mastectomy patients, with the dual aims of preserving oncologic safety while minimizing long-term treatment-related morbidity. The limitations of this study include the use of data from a single center with a limited sample size, which may affect the generalizability of the findings. As the data were extracted from real-world clinical practice, the lack of randomization between patients with and without FS introduces the potential for confounding factors. Although our team made efforts to minimize loss to follow-up, we acknowledge that a small number of patients with incomplete follow-up may have influenced the results. Nevertheless, our findings suggest that omitting FS in favor of PS does not compromise oncologic safety and may streamline surgical workflows. Conclusions In conclusion, we recommend reconsidering the routine use of intraoperative FS during SLNB for early-stage breast cancer. PS-only evaluation is safe, effective, and consistent with global trends and modern evidence-based practices. Declarations Conflict of Interest Statement The authors have no conflicts of interest to declare Statement of Ethics The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study protocol was reviewed and approved by the Institutional review board of faculty of medicine, Chulalongkorn University on August 5, 2025, COA number: 0951/2025. Individual consent for this retrospective analysis was waived. Funding statement: No funding was available for this study. Author Contribution Nattanan Treeratanapun: Conceptualization, Data Curation, Validation, Formal analysis Investigation, Writing - Original Draft, Writing- Reviewing and Editing Bhoowit Lerttiendamrong: Conceptualization, Data Curation, Formal analysis, Investigation, Validation, Writing- Reviewing and Editing Voranaddha Vacharathit: Investigation , Writing- Reviewing and Editing Kasaya Tantiphlachiva: Investigation Phuphat Vongwattanakit: Investigation Sopark Manasnayakorn: Investigation Mawin Vongsaisuwon: Conceptualization, Methodology, Supervision, Validation, Writing - Review & Editing Acknowledgement The authors received no contribution in this study. Data Availability The Datasets generated and/or analyzed in the current study are not publicly available due to the individuals privacy issue but are available from the corresponding author on reasonable request References Lyman GH, Somerfield MR, Bosserman LD, Perkins CL, Weaver DL, Giuliano AE. Sentinel Lymph Node Biopsy for Patients With Early-Stage Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2017;35:561-4. Wang Z, Wu LC, Chen JQ. Sentinel lymph node biopsy compared with axillary lymph node dissection in early breast cancer: a meta-analysis. Breast Cancer Res Treat 2011;129:675-89. Bartels SAL, Donker M, Poncet C, Sauvé N, Straver ME, van de Velde CJH, et al. Radiotherapy or Surgery of the Axilla After a Positive Sentinel Node in Breast Cancer: 10-Year Results of the Randomized Controlled EORTC 10981-22023 AMAROS Trial. 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Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 09 May, 2026 Reviews received at journal 08 May, 2026 Reviewers agreed at journal 08 May, 2026 Reviewers agreed at journal 01 May, 2026 Reviews received at journal 22 Mar, 2026 Reviewers agreed at journal 12 Mar, 2026 Reviewers invited by journal 12 Mar, 2026 Editor assigned by journal 04 Mar, 2026 Submission checks completed at journal 26 Feb, 2026 First submitted to journal 24 Feb, 2026 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. 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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-8959199","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":605295255,"identity":"bb81b9bc-7137-4723-b9e0-63f28215da89","order_by":0,"name":"Nattanan Treeratanapun","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"prefix":"","firstName":"Nattanan","middleName":"","lastName":"Treeratanapun","suffix":""},{"id":605295257,"identity":"936d4642-99d6-4ae1-8705-bfbc27fbb77e","order_by":1,"name":"Voranaddha Vacharathit","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"prefix":"","firstName":"Voranaddha","middleName":"","lastName":"Vacharathit","suffix":""},{"id":605295258,"identity":"ceb269b9-782e-4239-8aa8-ade075dfdeee","order_by":2,"name":"Kasaya Tantiphlachiva","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"prefix":"","firstName":"Kasaya","middleName":"","lastName":"Tantiphlachiva","suffix":""},{"id":605295262,"identity":"4aad0cb2-1072-45d6-8259-b102c0a31332","order_by":3,"name":"Phuphat Vongwattanakit","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"prefix":"","firstName":"Phuphat","middleName":"","lastName":"Vongwattanakit","suffix":""},{"id":605295270,"identity":"9b2c0287-b17e-4314-84fb-deed3c60d94b","order_by":4,"name":"Sopark Manasnayakorn","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"prefix":"","firstName":"Sopark","middleName":"","lastName":"Manasnayakorn","suffix":""},{"id":605295271,"identity":"44808799-6933-4953-a0c7-7ca8cf32a1df","order_by":5,"name":"Mawin Vongsaisuwon","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYJCCA0AsxyDBwHgAwuchTosxUAsDRAsbEVpAILGBaC267WcMDxcwHE7vn91jcOAHg508g3zvAbxazM7kGByewXA4d8adMwYHexiSDRvY+BLwazmQu+EwD0Na7gaJHIMDPAzMCUCHGeDXcv4tWEu6AVDLwT8M9URouQG2xSYBpAXIOEyMlvcfDvMY2BjOuJFWcFjG4LhhG1sOIYelJX/mqZCQ55+RvPHhm4pqeX7mM/i1QIABEoONCPWjYBSMglEwCggAAAHuQN+K8HCYAAAAAElFTkSuQmCC","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":true,"prefix":"","firstName":"Mawin","middleName":"","lastName":"Vongsaisuwon","suffix":""}],"badges":[],"createdAt":"2026-02-24 15:39:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8959199/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8959199/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105195550,"identity":"64df8f18-8edf-40cf-a84d-fb80bfd794b5","added_by":"auto","created_at":"2026-03-23 10:13:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":107353,"visible":true,"origin":"","legend":"\u003cp\u003ePatient selection flow chart. SLNB, sentinel lymph node biopsy; PS, permanent section; FS, frozen section.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8959199/v1/9a169776b9c754c84e5b9ee2.png"},{"id":105195456,"identity":"83d3b72f-3d89-442f-ae12-c935f77223fb","added_by":"auto","created_at":"2026-03-23 10:13:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":122963,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan Meier curve of Disease-Free Survival, Overall survival, Local Recurrences, Regional Recurrences, and Distant Metastases. SLNB, sentinel lymph node biopsy; PS, permanent section; FS, frozen section; BCT, breast-conserving therapy.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8959199/v1/e4e21b62b5c09785e76876e9.png"},{"id":105751840,"identity":"1006a8f1-5004-4ba4-b7f5-d899bd2a6a19","added_by":"auto","created_at":"2026-03-30 15:47:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":847368,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8959199/v1/2e42a87a-4585-471a-9153-71c667bbc561.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eSentinel lymph node biopsy without frozen section in mastectomy patients: A 5-year survival analysis from King Chulalongkorn Memorial Hospital\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSLNB has become the standard technique for axillary staging in clinically node-negative breast cancer, offering equivalent prognostic information to ALND with significantly less morbidity\u003csup\u003e(1)\u003c/sup\u003e. Traditionally, FS analysis has been employed during SLNB to identify nodal metastases intraoperatively, allowing immediate ALND when necessary and minimizing the need for reoperation\u003csup\u003e(2)\u003c/sup\u003e. However, this practice has been increasingly challenged by evidence suggesting limited clinical benefit from routine FS. The AMAROS trial and SENOMAC trial has incorporated treatment algorithms in which ALND was generally reserved for patients with a higher axillary nodal burden, typically defined as involvement of more than two sentinel lymph nodes\u003csup\u003e(3, 4)\u003c/sup\u003e. This paradigm has important implications for the role of FS analysis of sentinel lymph nodes. Because ALND would only be indicated when three or more sentinel lymph nodes are positive, FS would need to reliably identify multiple involved nodes during surgery to meaningfully alter immediate surgical management. Therefore, in the context of modern axillary de-escalation strategies supported by AMAROS and SENOMAC, routine FS offers limited incremental clinical benefit for mastectomy patients. Its continued use may increase operative time, resource utilization, and healthcare costs without translating into improved survival outcomes. Intraoperative FS has demonstrated inconsistent sensitivity particularly for micrometastases and false-negative rates ranging from 10% to 30%\u003csup\u003e(5, 6)\u003c/sup\u003e. Recent meta-analyses have questioned its necessity, especially in light of evolving guidelines that favor SLNB-only strategies for selected node-positive patients\u003csup\u003e(6, 7)\u003c/sup\u003e. Moreover, concerns have been raised about discordance between FS and final pathology results, further limiting FS\u0026rsquo;s impact on clinical decision-making \u003csup\u003e(8)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur prior retrospective study from King Chulalongkorn Memorial Hospital examined the clinical value of FS during SLNB in patients with early-stage breast cancer undergoing mastectomy\u003csup\u003e(9)\u003c/sup\u003e. This study showed that omission of FS did not lead to higher reoperation rates or worse short-term outcomes, and that most patients with positive sentinel lymph nodes did not require additional axillary treatment when managed according to the SENOMAC trial criteria\u003csup\u003e(4)\u003c/sup\u003e. Nevertheless, the scope of those analyses was confined to perioperative and short-term clinical endpoints, leaving long-term oncologic outcomes unaddressed. The current study extends this work by providing a 5-year follow-up of the same patient cohort treated with SLNB with or without intraoperative FS during mastectomy. Its objective is to evaluate disease-free survival and overall survival, and to determine whether omission of intraoperative FS affects long-term oncologic safety in this clinical context.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis retrospective study explored the five-year survival outcomes of early-stage breast cancer patients after being treated with different SLNB techniques. The primary focus was comparing the DFS between the FS and PS groups. Overall survival, recurrence at local and regional levels, and distant metastases, were also reported as secondary outcomes. We included all patients who had undergone SLNB procedure at KCMH from December 2017 to December 2022, with follow-up ending on December 15, 2025. The inclusion criteria were patients with early-stage breast cancer (T1 or T2) with clinically node-negative status and had undergone mastectomy and SLNB. Patients who had received neoadjuvant chemotherapy and non-invasive breast cancer patients were included. A total of 265 SLNB cases were included, in which 63 patients had undergone SLNB using PS alone and 202 patients undergone the FS technique (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDemographic, clinical, pathological, and treatment-related data including age, type of breast surgery, final histopathologic diagnosis, pathologic tumor stage (AJCC staging system), Nottingham histologic grade, presence of lymphovascular invasion, estrogen receptor, progesterone receptor, and HER2 status, as well as receipt of adjuvant systemic therapy and post mastectomy radiotherapy (PMRT) were extracted from medical records. Clinicopathologic characteristics were compared between patients undergoing SLNB with intraoperative frozen section (FS) and those evaluated by permanent section (PS) alone. Clinical nodal status was assessed by physical examination, and radiologic nodal evaluation was performed using breast ultrasonography with or without mammography, in accordance with standard preoperative staging practices. Sentinel lymph node mapping was performed using isosulfan blue dye as a single-agent tracer, which represents the standard SLNB technique at King Chulalongkorn Memorial Hospital and is widely used in Thailand. Pathologic evaluation of sentinel lymph nodes was performed using serial sectioning with hematoxylin and eosin staining, supplemented by immunohistochemistry when indicated. Written informed consent was waived due to the retrospective nature of the study.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData extracted from medical records were collected and managed using Microsoft Excel 2019. Statistical analyses were performed with IBM SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA). Categorical variables were summarized as frequencies and percentages and compared using the Pearson chi-square test or Fisher\u0026rsquo;s exact test, as appropriate. Disease-free survival (DFS) was defined as the interval from the SLNB procedure to the occurrence of any event, including local breast recurrence, ipsilateral axillary recurrence, distant metastasis, or death from any cause. Overall survival (OS) was defined as the time from SLNB to death from any cause. Local recurrence was defined as tumor recurrence within the breast, while regional recurrence referred to ipsilateral axillary events. Survival curves were estimated using the Kaplan\u0026ndash;Meier method and compared between the FS and PS groups using the log-rank test. For the primary endpoint of 5-year DFS, a noninferiority margin of 2.5% was prespecified, with 80% power and a one-sided type I error rate of 5%. As a secondary endpoint, cumulative incidences of local, regional, and distant recurrence were reported for both groups. A two-sided p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant for all analyses. For patients who experienced death or were lost to follow-up, the time from SLNB to the last known event or follow-up was recorded.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 265 SLNB procedures met the inclusion criteria and were included in the analysis. FS evaluation was performed in 202 cases, while 63 cases underwent PS evaluation alone. The median follow-up duration was 5.7 years (interquartile range [IQR], 4.8\u0026ndash;6.7) in the FS group and 4.8 years (IQR, 3.5\u0026ndash;5.8) in the PS group. Patient age ranged from 34 to 86 years, with a mean age of 55.8 years and a median age of 57.0 years. Comparisons of baseline clinicopathological characteristics between the FS and PS groups are summarized in Table\u0026nbsp;1. Seven histopathological subtypes were identified, including invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), ductal carcinoma in situ with micrometastasis (DCISM), mucinous carcinoma, papillary carcinoma, tubular carcinoma, and mixed invasive carcinoma. IDC was the predominant subtype, accounting for 204 cases (77.0%). Only one patient in the PS group underwent a second operation for completion ALND. HER2 immunohistochemistry status was unavailable in 11 patients due to equivocal results without subsequent fluorescence in situ hybridization testing. Statistically significant differences were observed between the FS and PS groups with respect to tumor size, hormone receptor status, and the use of ALND.\u003c/p\u003e\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 624px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e:\u0026nbsp;Comparison of Tumor Clinicopathology and Radiolographic nodal status between Frozen section and Permanent section group.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eFrozen section group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003ePermanent section group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eAge (yr)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e55.76\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e55.69 \u0026plusmn; 12.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e55.96 \u0026plusmn; 13.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.866\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eTumor size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;T1 (\u0026lt; 2 cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e96 (47.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e43 (68.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;T2 (2-5 cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e131\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e106 (52.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e20 (31.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eHistologic grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.567\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e41 (20.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e9 (14.3%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e131\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e98 (48.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e33 (52.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e63 (31.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e21 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eHistopathology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.092\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;IDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e204\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e164 (81.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e45 (71.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;ILC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e9 (4.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e5 (7.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;DCISM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e30\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e13 (6.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e10 (15.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Mucinous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e7\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e7 (3.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Papillary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e5 (2.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e3 (4.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Tubular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1 (0.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Metaplastic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e3 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eLymphovascular Invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.097\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e60 (29.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e12 (19.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e195\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e142 (70.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e51 (81.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eEstrogen receptor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;Positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e195\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e156 (77.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e37 (58.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;Negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e46 (22.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e26 (41.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eProgesterone receptor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;Positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e170\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e138 (68.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e32 (50.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;Negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e64 (31.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e31 (49.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eHER-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.725\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;Positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e61 (30.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e22 (34.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;Negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e172\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e133 (65.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e38 (60.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e8 (4.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e3 (4.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eALND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e49 (24.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1 (1.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e215\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e153 (75.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e62 (98.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eAdjuvant Hormonal Treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.068\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e142\u0026nbsp;(70.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e36\u0026nbsp;(51.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e60\u0026nbsp;(29.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e27\u0026nbsp;(56.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eAdjuvant Chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.113\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e146\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e117\u0026nbsp;(57.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e29\u0026nbsp;(46.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e85\u0026nbsp;(42.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e34 (54.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eAdjuvant Radiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.044\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e57 (28.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e27 (42.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e181\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e145 (71.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e36 (57.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eTargeted therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.413\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e32 (15.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e9 (14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e224\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e170 (84.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e54 (85.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e265\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 624px;\"\u003e\n \u003cp\u003eValues are represented as numbers (%) or mean \u0026plusmn; standard deviation.\u003c/p\u003e\n \u003cp\u003eIDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; DCISM, ductal carcinoma in situ with microinvasion; HER-2, human epidermal growth factor receptor 2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003cp\u003eThe 5-year DFS rate was 92.1% in the FS group and 93.7% in the PS group, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e2\u003c/span\u003eA. The PS group was noninferior to the FS group with respect to DFS, with a HR of 0.96 (95% CI, 0.28\u0026ndash;3.35) and a noninferiority P-value of 0.952. OS was comparable between groups (HR, 1.09; 95% CI, 0.13\u0026ndash;9.17; noninferiority P\u0026thinsp;=\u0026thinsp;0.937), as illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e2\u003c/span\u003eB. Five deaths (2.5%) occurred in the FS group, whereas no deaths were observed in the PS group during follow-up. Subgroup analyses according to tumor size, ALND status, and HER2 status showed consistent findings, with no statistically significant associations between these factors and disease recurrence (adjusted HR, 1.34 (95% CI, 0.44\u0026ndash;4.26; P\u0026thinsp;=\u0026thinsp;0.578), 1.13 (95% CI, 0.32\u0026ndash;2.99; P\u0026thinsp;=\u0026thinsp;0.851), and 1.33 (95% CI, 0.44\u0026ndash;4.05; P\u0026thinsp;=\u0026thinsp;0.613), respectively). Cumulative oncologic outcomes at 5 years are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e2\u003c/span\u003e. In the FS group, three patients (1.5%) experienced local breast recurrence, four patients (2.0%) developed regional (axillary) recurrence, and eight patients (4.0%) developed distant metastases. In the PS group, one patient (1.6%) had a local recurrence, one patient (1.6%) experienced axillary recurrence, and two patients (3.2%) developed distant metastases. No statistically significant differences were observed between groups for any oncologic outcome, as demonstrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e2\u003c/span\u003eA\u0026ndash;E.\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 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of 5-year survival outcomes\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLocal recurrences\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo. of event in FS group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo. of event in PS group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP- value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (1.5%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.6%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.667\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegional recurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (2.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.657\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistant metastases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.559\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeaths\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.253\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease-free survival\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (7.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.457\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eValues are represented as number.\u003c/p\u003e \u003cp\u003eFS, frozen section; PS, permanent section.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eFS of sentinel lymph nodes was historically adopted primarily to avoid a second operation by enabling immediate ALND when nodal metastases were identified intraoperatively\u003csup\u003e(10, 11)\u003c/sup\u003e. However, the contemporary evidence base has narrowed the indications for ALND after SLNB. In patients undergoing mastectomy who otherwise meet criteria for axillary de-escalation, multiple trials have established that with the post-mastectomy radiotherapy (PMRT), completion ALND can be safely omitted when only one or two sentinel nodes are involved, with no detriment in long-term oncologic outcomes. As a result, the potential benefit of FS is now largely confined to the scenario in which more than two sentinel nodes are positive, because only then would intraoperative identification be expected to alter management by prompting immediate ALND\u003csup\u003e(3, 4)\u003c/sup\u003e. Moreover, this paradigm has been increasingly questioned in the modern era, as systemic therapy and regional nodal irradiation have reduced the clinical impact of low-volume nodal disease\u003csup\u003e(12, 13)\u003c/sup\u003e. Consistent with this shift, an expanding body of literature supports that routine intraoperative FS can be omitted in early-stage breast cancer treated with breast-conserving surgery, without a clinically meaningful increase in reoperation rates\u003csup\u003e(14, 15)\u003c/sup\u003e. More recently, axillary de-escalation has progressed further: randomized evidence demonstrates that omission of SLNB in carefully selected patients undergoing primary breast-conserving surgery (typically clinically node-negative with negative preoperative axillary ultrasound and favorable biology) is noninferior to SLNB for key survival endpoints, supporting “no axillary surgery” approaches in defined low-risk groups\u003csup\u003e(16, 17)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eNevertheless, even in mastectomy populations where surgeons may be more reluctant to de-escalate axillary management, some studies have questioned the routine use of intraoperative FS because it often does not translate into a meaningful reduction in reoperations, particularly as ALND thresholds have become more restrictive and systemic/radiation strategies have evolved \u003csup\u003e(9, 18)\u003c/sup\u003e. In line with this, our previous institutional work also demonstrated that SLNB performed without intraoperative FS was not inferior in terms of reoperation rates, reinforcing the limited practical benefit of FS in contemporary management and supporting a PS-only strategy in appropriate patients\u003csup\u003e(9)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn this study, omission of FS during mastectomy for early-stage breast cancer did not compromise oncologic outcomes. At 5 years, disease-free survival (DFS) was 92.1% in the FS group and 93.7% in the permanent section (PS) group, with the PS strategy meeting predefined noninferiority criteria (HR, 0.96; 95% CI, 0.28–3.35; P = 0.952). These results indicate that omission of FS does not increase the risk of disease recurrence when treatment decisions are guided by final pathology and contemporary multimodality therapy, consistent with prior institutional and multi-institutional series evaluating FS omission in mastectomy patients\u003csup\u003e(12, 19, 20)\u003c/sup\u003e. Patterns of recurrence further reinforce the oncologic equivalence of the two approaches. Local recurrence occurred in 1.5% of patients in the FS group and 1.6% in the PS group, while regional (axillary) recurrence rates were 2.0% and 1.6%, respectively. Distant metastases developed in 4.0% of FS patients and 3.2% of PS patients, with no statistically significant differences across any oncologic endpoint. These low recurrence rates are comparable to those reported in modern mastectomy studies and support the safety of delayed axillary management based on permanent pathology\u003csup\u003e(3, 4, 21)\u003c/sup\u003e. An interesting observation in our cohort was the numerically higher incidence of overall recurrence incidences in the FS group, although these differences were not statistically significant. Notably, rare late overall locoregional and distant metastases occurring beyond eight years in the both groups raise questions regarding the long-term reliability of FS-based decision-making. A similar pattern of late recurrence following SLNB has been reported, underscoring the importance of extended follow-up in de-escalation studies\u003csup\u003e(22)\u003c/sup\u003e. In one cohort of clinically node-negative patients undergoing upfront mastectomy, omission of FS significantly reduced unnecessary ALND without adversely affecting oncologic outcomes\u003csup\u003e(19, 23)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eContemporary axillary management for patients with early-stage breast cancer undergoing mastectomy and found to have one to two positive sentinel lymph nodes has increasingly shifted toward postmastectomy radiotherapy (PMRT) rather than routine completion ALND\u003csup\u003e(24, 25)\u003c/sup\u003e. This paradigm change is supported by randomized evidence demonstrating comparable locoregional control between axillary radiotherapy and ALND, as shown in the SENOMAC, AMAROS, and OTOASOR trials\u003csup\u003e(3, 4, 21)\u003c/sup\u003e. As a result, PMRT has emerged as a preferred strategy in appropriately selected patients, offering effective regional control while reducing treatment-related morbidity associated with more extensive axillary surgery. Looking forward, ongoing prospective trials are expected to further refine axillary treatment by identifying subsets of node-positive patients who may safely avoid both ALND and PMRT. Studies such as POSNOC trial and T-REX trial are evaluating whether carefully selected patients, particularly those with hormone receptor–positive, HER2-negative, biologically low-risk tumors and limited nodal involvement, can achieve excellent oncologic outcomes with SLNB alone\u003csup\u003e(26, 27)\u003c/sup\u003e. Collectively, these efforts reflect a continued movement toward axillary de-escalation in mastectomy patients, with the dual aims of preserving oncologic safety while minimizing long-term treatment-related morbidity.\u003c/p\u003e \u003cp\u003eThe limitations of this study include the use of data from a single center with a limited sample size, which may affect the generalizability of the findings. As the data were extracted from real-world clinical practice, the lack of randomization between patients with and without FS introduces the potential for confounding factors. Although our team made efforts to minimize loss to follow-up, we acknowledge that a small number of patients with incomplete follow-up may have influenced the results. Nevertheless, our findings suggest that omitting FS in favor of PS does not compromise oncologic safety and may streamline surgical workflows.\u003c/p\u003e \u003cp\u003e\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, we recommend reconsidering the routine use of intraoperative FS during SLNB for early-stage breast cancer. PS-only evaluation is safe, effective, and consistent with global trends and modern evidence-based practices.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of Interest Statement\u003c/h2\u003e \u003cp\u003eThe authors have no conflicts of interest to declare\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eStatement of Ethics\u003c/h2\u003e \u003cp\u003eThe authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study protocol was reviewed and approved by the Institutional review board of faculty of medicine, Chulalongkorn University on August 5, 2025, COA number: 0951/2025. Individual consent for this retrospective analysis was waived.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding statement:\u003c/h2\u003e \u003cp\u003eNo funding was available for this study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eNattanan Treeratanapun: Conceptualization, Data Curation, Validation, Formal analysis Investigation, Writing - Original Draft, Writing- Reviewing and Editing Bhoowit Lerttiendamrong: Conceptualization, Data Curation, Formal analysis, Investigation, Validation, Writing- Reviewing and Editing Voranaddha Vacharathit: Investigation , Writing- Reviewing and Editing Kasaya Tantiphlachiva: Investigation Phuphat Vongwattanakit: Investigation Sopark Manasnayakorn: Investigation Mawin Vongsaisuwon: Conceptualization, Methodology, Supervision, Validation, Writing - Review \u0026amp; Editing\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e \u003cp\u003eThe authors received no contribution in this study.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe Datasets generated and/or analyzed in the current study are not publicly available due to the individuals privacy issue but are available from the corresponding author on reasonable request\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLyman GH, Somerfield MR, Bosserman LD, Perkins CL, Weaver DL, Giuliano AE. Sentinel Lymph Node Biopsy for Patients With Early-Stage Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2017;35:561-4.\u003c/li\u003e\n\u003cli\u003eWang Z, Wu LC, Chen JQ. Sentinel lymph node biopsy compared with axillary lymph node dissection in early breast cancer: a meta-analysis. Breast Cancer Res Treat 2011;129:675-89.\u003c/li\u003e\n\u003cli\u003eBartels SAL, Donker M, Poncet C, Sauv\u0026eacute; N, Straver ME, van de Velde CJH, et al. Radiotherapy or Surgery of the Axilla After a Positive Sentinel Node in Breast Cancer: 10-Year Results of the Randomized Controlled EORTC 10981-22023 AMAROS Trial. J Clin Oncol 2023;41:2159-65.\u003c/li\u003e\n\u003cli\u003ede Boniface J, Filtenborg Tvedskov T, Ryd\u0026eacute;n L, Szulkin R, Reimer T, K\u0026uuml;hn T, et al. Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases. N Engl J Med 2024;390:1163-75.\u003c/li\u003e\n\u003cli\u003eFrancissen CM, van la Parra RF, Mulder AH, Bosch AM, de Roos WK. Evaluation of the benefit of routine intraoperative frozen section analysis of sentinel lymph nodes in breast cancer. ISRN Oncol 2013;2013:843793.\u003c/li\u003e\n\u003cli\u003eElshanbary AA, Awad AA, Abdelsalam A, Ibrahim IH, Abdel-Aziz W, Darwish YB, et al. The diagnostic accuracy of intraoperative frozen section biopsy for diagnosis of sentinel lymph node metastasis in breast cancer patients: a meta-analysis. Environ Sci Pollut Res Int 2022;29:47931-41.\u003c/li\u003e\n\u003cli\u003eBharath S, Sharma D, Yadav SK, Shekhar S, Jha CK. A Systematic Review and Meta-analysis of Touch Imprint Cytology and Frozen Section Biopsy and Their Comparison for Evaluation of Sentinel Lymph Node in Breast Cancer. World J Surg 2023;47:478-88.\u003c/li\u003e\n\u003cli\u003eGeertsema D, Gobardhan PD, Madsen EV, Albregts M, van Gorp J, de Hooge P, et al. Discordance of intraoperative frozen section analysis with definitive histology of sentinel lymph nodes in breast cancer surgery: complementary axillary lymph node dissection is irrelevant for subsequent systemic therapy. Ann Surg Oncol 2010;17:2690-5.\u003c/li\u003e\n\u003cli\u003eVongsaisuwon M, Vacharathit V, Lerttiendamrong B, Manasnayakorn S, Tantiphlachiva K, Vongwattanakit P, et al. Reconsidering the Role of Frozen Section in Sentinel Lymph Node Biopsy for Mastectomy Patients. J Surg Res 2024;293:64-70.\u003c/li\u003e\n\u003cli\u003eChao C, Wong SL, Ackermann D, Simpson D, Carter MB, Brown CM, et al. Utility of intraoperative frozen section analysis of sentinel lymph nodes in breast cancer. Am J Surg 2001;182:609-15.\u003c/li\u003e\n\u003cli\u003eBarakat FH, Sulaiman I, Sughayer MA. Reliability of frozen section in breast sentinel lymph node examination. Breast Cancer 2014;21:576-82.\u003c/li\u003e\n\u003cli\u003eSi J, Guo R, Pan H, Lu X, Guo Z, Han C, et al. Axillary Lymph Node Dissection Can Be Omitted in Breast Cancer Patients With Mastectomy and False-Negative Frozen Section in Sentinel Lymph Node Biopsy. Front Oncol 2022;12:869864.\u003c/li\u003e\n\u003cli\u003ePoling JS, Tsangaris TN, Argani P, Cimino-Mathews A. Frozen section evaluation of breast carcinoma sentinel lymph nodes: a retrospective review of 1,940 cases. Breast Cancer Res Treat 2014;148:355-61.\u003c/li\u003e\n\u003cli\u003eTreeratanapun N, Lerttiendamrong B, Vacharathit V, Tantiphlachiva K, Vongwattanakit P, Manasnayakorn S, et al. Is sentinel lymph node biopsy without frozen section in early stage breast cancer sufficient in accordance with ACOSOG-Z0011? A retrospective review from King Chulalongkorn Memorial Hospital. BMC Surg 2022;22:261.\u003c/li\u003e\n\u003cli\u003eLerttiendamrong B, Treeratanapun N, Vacharathit V, Tantiphlachiva K, Vongwattanakit P, Manasnayakorn S, et al. Is Routine Intraoperative Frozen Section Analysis of Sentinel Lymph Nodes Necessary in Every Early-Stage Breast Cancer? Breast Cancer (Dove Med Press) 2022;14:281-90.\u003c/li\u003e\n\u003cli\u003eGentilini OD, Botteri E, Sangalli C, Galimberti V, Porpiglia M, Agresti R, et al. Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes: The SOUND Randomized Clinical Trial. JAMA Oncol 2023;9:1557-64.\u003c/li\u003e\n\u003cli\u003eReimer T, Stachs A, Veselinovic K, K\u0026uuml;hn T, Heil J, Polata S, et al. Axillary Surgery in Breast Cancer - Primary Results of the INSEMA Trial. N Engl J Med 2025;392:1051-64.\u003c/li\u003e\n\u003cli\u003eAydin F, Kulturoglu MO, Aslan F, Dogan L. Intraoperative frozen section analysis can be omitted in early breast cancer without significantly elevating reoperation rates. BMC Surg 2025;25:347.\u003c/li\u003e\n\u003cli\u003eWilliams AD, Khan AJ, Sevilimedu V, Barrio AV, Morrow M, Mamtani A. Omission of Intraoperative Frozen Section May Reduce Axillary Overtreatment Among Clinically Node-Negative Patients Having Upfront Mastectomy. Ann Surg Oncol 2022;29:8037-43.\u003c/li\u003e\n\u003cli\u003eSargent RE, Barrio AV, Sevilimedu SV, Khan AJ, Morrow M, Mamtani A. Omission of Routine Frozen Section for Clinically Node-Negative Patients Undergoing Upfront Mastectomy Avoids Unnecessary Axillary Treatment. Ann Surg Oncol 2025.\u003c/li\u003e\n\u003cli\u003eS\u0026aacute;volt \u0026Aacute;, P\u0026eacute;ley G, Polg\u0026aacute;r C, Udvarhelyi N, Rubovszky G, Kov\u0026aacute;cs E, et al. Eight-year follow up result of the OTOASOR trial: The Optimal Treatment Of the Axilla - Surgery Or Radiotherapy after positive sentinel lymph node biopsy in early-stage breast cancer: A randomized, single centre, phase III, non-inferiority trial. Eur J Surg Oncol 2017;43:672-9.\u003c/li\u003e\n\u003cli\u003eCarleton N, Zou J, Fang Y, Koscumb SE, Shah OS, Chen F, et al. Outcomes After Sentinel Lymph Node Biopsy and Radiotherapy in Older Women With Early-Stage, Estrogen Receptor-Positive Breast Cancer. JAMA Netw Open 2021;4:e216322.\u003c/li\u003e\n\u003cli\u003ePride RM, Glass CC, Nakhlis F, Laws A, Weiss AC, Bellon JR, et al. Intraoperative Pathology Assessment May Lead to Overtreatment of the Axilla in Clinically Node-Negative Breast Cancer Patients Undergoing Upfront Mastectomy. Ann Surg Oncol 2023;30:5978-87.\u003c/li\u003e\n\u003cli\u003eWeiss A, Lin H, Babiera GV, Bedrosian I, Shaitelman SF, Shen Y, et al. Evolution in practice patterns of axillary management following mastectomy in patients with 1-2 positive sentinel nodes. Breast Cancer Res Treat 2019;176:435-44.\u003c/li\u003e\n\u003cli\u003eVerreck EEF, van Steenhoven JEC, Kuijer A, van Maaren MC, Simons JM, Siesling S, et al. Trends of Axillary Treatment in Sentinel Node-Positive Breast Cancer Patients Undergoing Mastectomy. Ann Surg Oncol 2023;30:5623-32.\u003c/li\u003e\n\u003cli\u003eAlkner S, de Boniface J, Lundstedt D, Mjaaland I, Ryden L, Vikstrom J, et al. Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases - an open, multicentre, randomised non-inferiority phase 3 trial. BMJ Open 2023;13:e075543.\u003c/li\u003e\n\u003cli\u003eGoyal A, Mann GB, Fallowfield L, Duley L, Reed M, Dodwell D, et al. POSNOC-POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy: a randomised controlled trial of axillary treatment in women with early-stage breast cancer who have metastases in one or two sentinel nodes. BMJ Open 2021;11:e054365.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"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":"Permanent section (PS), Frozen section (FS), Early-stage breast cancer, Sentinel lymph node biopsy (SLNB)","lastPublishedDoi":"10.21203/rs.3.rs-8959199/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8959199/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIntraoperative frozen section (FS) during sentinel lymph node biopsy (SLNB) has traditionally been used to facilitate immediate axillary lymph node dissection (ALND). However, contemporary axillary de-escalation strategies supported by AMAROS and SENOMAC trials have narrowed indications for ALND, raising questions about the clinical value of routine FS, particularly in mastectomy patients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed early-stage breast cancer patients (T1\u0026ndash;T2, clinically node-negative) who underwent mastectomy with SLNB at a single institution between 2017 and 2022. Patients were managed with either intraoperative FS or permanent section (PS) alone. The primary endpoint was 5-year disease-free survival (DFS) using a noninferiority design. Secondary endpoints included overall survival (OS) and patterns of recurrence.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 265 patients, 202 underwent SLNB with FS and 63 with PS alone. Median follow-up was 5.7 and 4.8 years, respectively. Five-year DFS was 92.1% in the FS group and 93.7% in the PS group. The PS strategy was noninferior to FS (hazard ratio [HR], 0.96; 95% CI, 0.28\u0026ndash;3.35; noninferiority P\u0026thinsp;=\u0026thinsp;0.952). Overall survival was comparable (HR, 1.09; 95% CI, 0.13\u0026ndash;9.17). Rates of local, regional, and distant recurrence did not differ significantly. Only one patient in the PS group required delayed ALND.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOmission of intraoperative FS during SLNB in mastectomy patients did not compromise long-term oncologic outcomes. A PS-only strategy appears safe and supports further axillary de-escalation in contemporary practice.\u003c/p\u003e","manuscriptTitle":"Sentinel lymph node biopsy without frozen section in mastectomy patients: A 5-year survival analysis from King Chulalongkorn Memorial Hospital","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-23 10:11:58","doi":"10.21203/rs.3.rs-8959199/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-09T13:52:52+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-09T01:40:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"105521899774409949018274823683039642810","date":"2026-05-09T01:35:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"232015008291614277477135157493475862024","date":"2026-05-01T12:58:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-22T15:26:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"215774213804610512924005771227344739393","date":"2026-03-12T20:55:09+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-12T09:44:31+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-04T06:08:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-26T09:29:44+00:00","index":"","fulltext":""},{"type":"submitted","content":"World Journal of Surgical Oncology","date":"2026-02-24T15:35:23+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":"3213d5cb-7c48-4c99-a396-b1c467602e1b","owner":[],"postedDate":"March 23rd, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-09T13:52:52+00:00","index":33,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-09T01:40:22+00:00","index":32,"fulltext":""},{"type":"reviewerAgreed","content":"105521899774409949018274823683039642810","date":"2026-05-09T01:35:41+00:00","index":31,"fulltext":""},{"type":"reviewerAgreed","content":"232015008291614277477135157493475862024","date":"2026-05-01T12:58:27+00:00","index":28,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-23T10:11:58+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-23 10:11:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8959199","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8959199","identity":"rs-8959199","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}