Frequency of Positive Margins and Predictors in Breast-Conserving Surgery in developing countries | 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 Frequency of Positive Margins and Predictors in Breast-Conserving Surgery in developing countries Sadaf Alipour, Bita Eslami, Nasim Nouri, Ramesh Omranipour, Samareh Heydari This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6148426/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Background Achieving negative surgical margins in breast-conserving surgery (BCS) is crucial due to the risks linked to positive margins, such as the need for reoperation and elevated local recurrence rates. Limited data exist about positive margins after BCS in developing countries, including Iran, and this study aims to close this gap by assessing the rates of positive margins in BCS and the factors that affect it. Method This retrospective study investigated breast cancer patients at Tehran University of Medical Sciences from 2003 to 2024. It included female patients who underwent breast-conserving surgery (BCS) and had complete data available. The rate of positive margins in histological assessment of surgical specimens and its relationship with various tumor and patient factors were explored using univariate and multivariate logistic model analyses. Result A total of 2,585 patients underwent BCS, with a median age of 49 and a mean tumor size of 27 mm. Free surgical margins were found in 91.4% of cases, while 8.6% exhibited involved margins, these underwent re-excision of the involved margin. A significant association was observed between younger patient age, tumor size, lymphovascular invasion, and margin involvement. Conclusion This study found a lower margin positivity rate in BCS than reported in the great part of the present literature, it also identified preoperative clinical and pathological factors linked to margin involvement, allowing for better risk prediction and potential surgical adjustments. Breast cancer Breast-conserving therapy (BCT) Positive surgical margin Re-operation Risk factors Background Achieving negative surgical margins besides cosmetic results is a critical determinant of success in breast-conserving surgery (BCS), as positive margins often necessitate re-operation and significantly increase the risk of local recurrence (ranging from 3.5–6.5%)( 1 – 5 ). While BCS, supported or not by oncoplastic techniques, has become one of the most preferred approaches for breast cancer treatment, especially for early-stage cancer, and aims to achieve oncological safety while preserving breast aesthetics, the rate of positive margins after this type of surgery varies widely across studies, ranging from 10–38% ( 2 , 6 – 12 ).These variations highlight the effect of factors such as tumor characteristics, institutional practices, and surgical techniques ( 5 , 10 , 13 , 14 ). Although margin status has been emphasized globally and widely studied, there is a lack of published data about the rate of positive margins following BCS in Iran, creating a gap in understanding the outcomes of this commonly performed procedure in the country. Previous studies have shown various factors that impact the likelihood of positive margins. These factors include tumor characteristics, such as histological subtype, size, molecular markers, lymphovascular invasion, and patient-related factors, such as age and body mass index. Additionally, surgical variables, including the type of surgery and surgeon’s experiment, have also been reported to impact margin status ( 5 , 13 – 19 ). Despite these insights, there is limited information about how these factors contribute to positive margin rates in Iran. In this study, we sought to evaluate the rate of positive margins in BCS cases performed in Iran and investigate the association of the likelihood of positive margins with clinicopathological factors. We aim to enhance surgical practices and patient outcomes in breast cancer treatment by comparing our findings with international data and incorporating surgeons' perspectives during this study. Material and Methods Settings, Participants, and Eligibility Criteria This retrospective study examined patients with breast cancer who underwent surgery at hospitals affiliated with Tehran University of Medical Sciences from March 2003 to September 2024. The research was approved by the Ethics Committee of TUMS (Approval ID: IR.TUMS.IKHC.REC.1402.229). Written informed consent was obtained from the patients for the use of their data in this study, and the study is conducted under the Declaration of Helsinki. The inclusion criteria consisted of the female sex, breast-conserving surgery (BCS), available demographic, surgical, histological, and molecular data; and availability of contact information. The exclusion criteria encompassed cases of rare breast cancers, such as sarcoma, malignant phyllode tumors, and neuroendocrine carcinoma. Variables, Measurements, and Outcomes Eligible patients were identified through a review of medical records and pathology data. Demographic information, including age, body mass index (BMI), clinical findings, relevant imaging results (ultrasonography, mammography, and MRI, when performed), and histological characteristics (tumor type, microscopic features, molecular subtype, tumor size, margin status, type and results of reoperation, and), was extracted. Additionally, information on menopausal status, history of abortion, infertility, blood type, smoking history, hormone therapy, oral contraceptive pill (OCP) use, and family history of breast cancer was collected. Tumor biological characteristics, such as grade, presence and type of metastasis, lymphovascular invasion (LVI), number of positive lymph nodes, hormone receptor status (estrogen receptor (ER), progesterone receptor (PR), and their respective percentages), HER2 status were documented. In cases of incomplete data, follow-up information was obtained by contacting patients or their relatives by phone. The relationship between positive surgical margins and various factors, including tumor grade, vascular and lymphatic invasion, lymph node involvement, pathology type, BMI, and was subsequently analyzed. The definition of a positive margin has been defined by the Society of Surgical Oncology (SSO) and the American Society for Radiation Oncology (ASTRO)( 20 ). Statistical Analysis The analysis for this study was conducted using SPSS version 24 (IBM Corp. 2016. IBM SPSS Statistics for Windows, version 24.0.Armonk, NY: IBM Corp). Quantitative variables were presented as means and standard deviations, while categorical variables were reported as counts and percentages. To compare quantitative variables between the two groups (involved and free margins) a Student T-test was utilized. For qualitative data, the chi-square test was used for comparison. Variables that showed a significance level below 0.05 in the univariate analysis were included in the multivariate logistic regression model. The odds ratio and 95% confidence intervals were calculated to assess the degree of association between the variables and involved margins. Results Over the years of our study, 2,585 patients underwent primary BCS in TUMS, with adequate pathology reports for margin status. The mean tumor size was 26.70 ± 16.92 mm, and the mean patient age was 49.11 ± 11.16, ranging from 18 to 88 years. Table 1 details all the patient and tumor characteristics. The pathological margins were free in 2,305 cases (91.4%), while involved margins were found in 216 patients (8.6%). Among the patients with free margins, 148 had close margins. Eighty-nine percent of cases involved invasive ductal carcinoma. Positive lymphovascular invasion was observed in 1,239 patients (54.2%). All patients with involved margins underwent a second surgery, which was either a margin re-excision or a mastectomy, depending on the surgeon's recommendation and the patient's preference. There were no additional instances of involved margins after the second surgery. Table 2 shows the relationship between the dependent variable (margin status) and various independent variables, including factors related to patients and tumors. Most patients (89.9%) with invasive ductal carcinoma (IDC) histology exhibited clear pathological margins. There was a significant association between patient age and margin status, indicating that younger patients tend to have more involved margin. Among all the tumor characteristics analyzed, only tumor size, pathology, lymphovascular invasion, and axillary lymph node invasion showed a significant association with margin status in univariate analysis. Of these factors, only tumor size (OR=1.02, 95%CI=1.01-1.03), lymphovascular invasion (OR=2.18, 95%CI=1.34-3.53), and patient age (OR=0.98, 95%CI= 0.96-0.99) remain significantly associated with margin involvement after multivariate analysis. Over the past 20 years, we observed a significant improvement in margin status, with a p-value of less than 0.001. The free margin increased from 0.6% reported in 2003 to 4.8% among 2024 patients. Discussion The current study found a positive margin rate of about 9% in Iran. We also analyzed patient outcomes and discovered that larger tumor sizes and younger ages are associated with involved margins after breast-conserving surgery (BCS), which is consistent with previous studies ( 21 – 26 ). Additionally, we identified lymphovascular invasion as a significant predictor of margin involvement. Since the involvement of surgical margins after breast-conserving surgery (BCS) is a significant predictor of local recurrence of the disease, failing to achieve negative margins often necessitates further surgery, such as re-excision or mastectomy( 27 ). Second surgeries raise costs for the health care system and the patients and may lead to larger post-surgical defects, worsening aesthetic outcomes, and delaying necessary adjuvant therapy ( 28 – 30 ). Reoperation rates after BCS vary significantly between centers and institutions ( 31 – 33 ). Each center should evaluate its performance metrics to determine effectiveness and identify areas for improvement. Also, identifying patient and tumor characteristics associated with involved margins before surgery would enhance patient counseling and assist the surgeon in making preoperative decisions before the first procedure. The 9% rate of margin positivity reported in the current study is lower than rates published by other centers, including a rate of 24% in Bahrain ( 34 ),11% in Canada ( 31 ), around 66% in Italy ( 5 ), and 25% in the Netherlands ( 35 ). The difference may stem from several factors. To evaluate the point of view of surgeons in our country regarding the rate of BCS positive margins in Iran in comparison with literature reports and also the reasons for any difference in their opinion, we surveyed 30 active breast surgeons using two dedicated multiple-choice questions asking exactly these two questions. The survey showed that most surgeons believed the margin involvement rate in Iran is lower than that in Western studies, and most attributed this to larger tissue resection during initial surgeries, as patients are strongly reluctant to undergo re-operations. This is probably true, and the most likely reason for a low margin-positivity is because of the initial wide margin excision due to patients' unacceptance of further excision. Other factors that can be mentioned include the high costs of radiotherapy and chemotherapy and the possibility of needing further treatments due to close margins. Baliski et al.( 1 ) study supports these findings, showing that a larger CRR (calculated resection ratio) is more indicative of free margins. It is important to highlight that a previous study by Akbari et al. in Iran ( 36 ) found a positive margin rate of 1–2%. The difference in our findings and the more reasonable and expectable rate in our study might be because of the higher sample size, and the multicentric nature of our study. The definition of margin status has changed over the years. Before the SSO-ASTRO introduced "no ink on the tumor" in 2014, surgeons had varied and conservative methods for assessing margins. A 1995 study, for example, defined a close margin as being 12 mm from the tumor edge( 16 , 27 ). Recent studies have suggested that the definition of a negative margin in the context of BCS should be reconsidered ( 37 , 38 ). Additionally, it has been noted that the rates of reoperation after BCS remain high ( 39 ), indicating a continuing need for quality improvement in this area. This could be addressed by enhancing intraoperative margin assessment techniques, using options like shaving cavity margins ( 2 , 28 ), or identifying predictors that contribute to an increased re-excision rate, which was done during this study. Our analyses indicated an improvement in the re-excision rate during the recent 20 years. This finding has occurred in many centers globally and is partly due to the change in guidelines and margin definitions, as shown in a meta-analysis by Marinovichet et al. ( 6 ) in 2020. The current study identifies tumor size and lymphovascular invasion as significant factors that correlate with positive margins. It indicates that larger tumors with positive lymphovascular invasion are at a higher risk of having pathologically positive margins. Previous studies have also shown that larger tumors tend to have more positive margins, ( 21 – 26 ) possibly due to the challenges of removing a large tumor while also considering cosmetic outcomes. Lymphovascular invasion has not been as frequently discussed as a predictor of margin status in studies compared to tumor size. However, Deurzan et al.'s multivariate analysis ( 25 ) demonstrates a significant association between positive angioinvasion and positive margins. In this study, the patient's age is also identified as a predictor of margin involvement, supporting previous data showing higher positive margins after initial BCS in younger patients( 11 , 34 , 40 ), particularly those under 40 ( 41 ), under 46 ( 23 ), or between 45 and 60 years old ( 26 ). Denser breast tissue in younger patients may lead to less accurate tumor size assessments before surgery. Additionally, younger patients often prioritize cosmetic outcomes, resulting in smaller excisions that can cause a higher rate of positive margins and require further surgery. ILC and DCIS were more often associated with involved margins, suggesting that these histologic subtypes may increase the likelihood of having involved margins, similar to the study of Ellbrant et al. ( 11 , 32 ). Still, it wasn’t statistically significant during our study. This is in contrast to a study by Krekel et al.( 42 ), who reported a lower positive margin rate for nonpalpable lesions, including DCIS. Furthermore, another study found no significant differences in margin status between palpable and nonpalpable tumors( 14 ). Nonetheless, mass formation is more common in IDC tumors, whereas DCIS or ILC may not present with obvious masses; this may explain the improved understanding of the cancer boundaries and limits by surgeons, leading to better margin resection in IDC. There is a slight increase in margin positivity among HER + patients, but this result was not statistically significant, possibly due to the smaller number of HER + patients compared to HR + patients. In general, our study aligns with Zavagno et al.'s findings( 5 ) regarding predictor factors, but it differs in the margin status rate. This indicates an improvement in BCS management over the years. Understanding the factors contributing to ineffectiveness can be beneficial. In Iran, the lack of national BC screening programs has led to the late detection of tumors, resulting in most tumors being palpable during initial physical examinations. Therefore, this study did not recognize a palpable tumor in the first physical examination as a predictor of margin status despite previous studies in other countries. This study had some limitations. The data was collected from University-affiliated hospitals in Tehran, which may not represent practice in all regions of Iran. Also, considering the retrospective nature of this study, incomplete data from earlier years may have influenced certain clinical variables, although efforts were made to supplement this information. It should be noted that this study provides the first comprehensive evaluation of positive margin rates in BCS in Iran and highlights the key factors contributing to margin status. Future prospective studies conducted across a broader range of hospitals in Iran, incorporating advanced intraoperative margin assessment tools, could help address these limitations. Conclusion In this study, we identified a lower margin positivity rate in BCS compared with studies from other countries. According to experts, this lower rate might be due to patients' unacceptance of reoperation. Also, various clinical and pathological factors significantly linked to involved resection margins were considered. Since most of these factors can be evaluated preoperatively, this presents an opportunity for improved risk prediction before surgery and potential adjustments to the surgical approach. Abbreviations BCS, BCT, BMI, LVI, ER, PR, HER2, OCP, IDC, ILC, DCIS, CRR Declarations Ethics approval and consent to participate: The research was approved by the Ethics Committee of TUMS (Approval ID: IR.TUMS.IKHC.REC.1402.229). The patients gave written informed consent for using their data in this study, which was conducted according to the Declaration of Helsinki. Consent for publication: Not applicable. Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request . Competing interests: The authors declare that they have no competing interests. Funding: Not applicable. Authors' contributions: Sadaf Alipour, Ramesh Omranipour, and Bita Eslami contributed to the study conception and design. Material preparation and data collection were performed by Samareh Heydari and Nasim Nouri. Statistical analysis was conducted by Bita Eslami. The first draft of the manuscript was written by Samareh Heydari and Nasim Nouri. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledgments We would like to acknowledge Drs. Negar Mashoori, Adel Yazadnkhah Kenary, Mandana Motamedi, Mahsa Tavakol, Maryam Sarkardeh, Ms. Mahta Mohammadzadeh, Shiller Hessamiazar, Samira Shabani, Fatemeh Mahmoodi, and Mr. Mohammadreza Mirzaee Goodarzi for their assistance in gathering the proper data. We also acknowledge the Deputy of Research of Tehran University of Medical Sciences for their financial support of the project. References Baliski C, Hughes L, Bakos B. Lowering Re-excision Rates After Breast-Conserving Surgery: Unraveling the Intersection Between Surgeon Case Volumes and Techniques. Ann Surg Oncol. 2021;28(2):894–901. Tamburelli F, Maggiorotto F, Marchiò C, Balmativola D, Magistris A, Kubatzki F, et al. Reoperation rate after breast conserving surgery as quality indicator in breast cancer treatment: A reappraisal. Breast. 2020;53:181–8. Landercasper J, Borgert AJ, Fayanju OM, Cody H 3rd, Feldman S, Greenberg C, et al. Factors Associated with Reoperation in Breast-Conserving Surgery for Cancer: A Prospective Study of American Society of Breast Surgeon Members. Ann Surg Oncol. 2019;26(10):3321–36. Anderson SJ, Wapnir I, Dignam JJ, Fisher B, Mamounas EP, Jeong JH, et al. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative breast cancer. J Clin Oncol. 2009;27(15):2466–73. Zavagno G, Goldin E, Mencarelli R, Capitanio G, Del Bianco P, Marconato R, et al. Role of resection margins in patients treated with breast conservation surgery. Cancer. 2008;112(9):1923–31. Marinovich ML, Noguchi N, Morrow M, Houssami N. Changes in Reoperation After Publication of Consensus Guidelines on Margins for Breast-Conserving Surgery: A Systematic Review and Meta-analysis. JAMA Surg. 2020;155(10):e203025. Aziz D, Rawlinson E, Narod SA, Sun P, Lickley HL, McCready DR, et al. The role of reexcision for positive margins in optimizing local disease control after breast-conserving surgery for cancer. Breast J. 2006;12(4):331–7. Kurniawan ED, Wong MH, Windle I, Rose A, Mou A, Buchanan M, et al. Predictors of surgical margin status in breast-conserving surgery within a breast screening program. Ann Surg Oncol. 2008;15(9):2542–9. Haloua MH, Volders JH, Krekel NM, Barbé E, Sietses C, Jóźwiak K, et al. A nationwide pathology study on surgical margins and excision volumes after breast-conserving surgery: There is still much to be gained. Breast. 2016;25:14–21. Rubio IT, Ahmed M, Kovacs T, Marco V. Margins in breast conserving surgery: A practice-changing process. Eur J Surg Oncol. 2016;42(5):631–40. Jung W, Kang E, Kim SM, Kim D, Hwang Y, Sun Y, et al. Factors Associated with Re-excision after Breast-Conserving Surgery for Early-Stage Breast Cancer. J Breast Cancer. 2012;15(4):412–9. Rossou C, Alampritis G, Patel B. Reducing re-excision rates in breast conserving surgery with Margin Probe: systematic review. Br J Surg. 2024;111(1). Touboul E, Buffat L, Belkacémi Y, Lefranc JP, Uzan S, Lhuillier P, et al. Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer. Int J Radiat Oncol Biol Phys. 1999;43(1):25–38. Srour MK, Manguso N, Mirocha J, Chung A, Giuliano AE, Amersi F. Impact of Resident and Fellow Participation on Surgical Outcomes in Breast Conserving Surgery for Invasive Breast Cancer. J Surg Educ. 2020;77(1):144–9. Cheun JH, Lee YJ, Lee JH, Shin Y, Chun JW, Baek SY, et al. Surgical margin status and survival outcomes of breast cancer patients treated with breast-conserving surgery and whole-breast irradiation after neoadjuvant chemotherapy. Breast Cancer Res Treat. 2022;194(3):683–92. Moran MS, Schnitt SJ, Giuliano AE, Harris JR, Khan SA, Horton J, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. J Clin Oncol. 2014;32(14):1507–15. Houssami N, Macaskill P, Marinovich ML, Dixon JM, Irwig L, Brennan ME, et al. Meta-analysis of the impact of surgical margins on local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy. Eur J Cancer. 2010;46(18):3219–32. Chakedis JM, Chang SB, Tang A, Kuehner GE, Savitz AC, Vuong B, et al. Assessment of Surgeon Factors Associated With Margin Re-excision After Breast-Conserving Surgery. JAMA Netw Open. 2022;5(8):e2228100. Biglia N, Ponzone R, Bounous VE, Mariani LL, Maggiorotto F, Benevelli C, et al. Role of re-excision for positive and close resection margins in patients treated with breast-conserving surgery. Breast. 2014;23(6):870–5. Morrow M, Van Zee KJ, Solin LJ, Houssami N, Chavez-MacGregor M, Harris JR, et al. Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma In Situ. J Clin Oncol. 2016;34(33):4040–6. Fisher S, Yasui Y, Dabbs K, Winget M. Re-excision and survival following breast conserving surgery in early stage breast cancer patients: a population-based study. BMC Health Serv Res. 2018;18(1):94. Bouzón A, Acea B, García A, Iglesias Á, Mosquera J, Santiago P, et al. Risk factors for positive margins in conservative surgery for breast cancer after neoadjuvant chemotherapy. Cir Esp. 2016;94(7):379–84. Hughes L, Hamm J, McGahan C, Baliski C. Surgeon Volume, Patient Age, and Tumor-Related Factors Influence the Need for Re-Excision After Breast-Conserving Surgery. Ann Surg Oncol. 2016;23(Suppl 5):656–64. Fauveau LR, Dao TN, Wallace LB, Mamawala MK, Obaid A, Waddimba AC, et al. Positive surgical margins after breast-conserving surgery for ductal carcinoma in-situ: does histologic grade or estrogen receptor status matter? Breast Cancer Res Treat. 2023;199(2):215–20. van Deurzen CH. Predictors of Surgical Margin Following Breast-Conserving Surgery: A Large Population-Based Cohort Study. Ann Surg Oncol. 2016;23(Suppl 5):627–33. Dhak S, Baliski C, Bakos B. Factors influencing suboptimal pathologic margins and re-excision following breast conserving surgery for ductal carcinoma in-situ. Am J Surg. 2023;225(5):866–70. Smitt MC, Nowels KW, Zdeblick MJ, Jeffrey S, Carlson RW, Stockdale FE, et al. The importance of the lumpectomy surgical margin status in long-term results of breast conservation. Cancer. 1995;76(2):259–67. Mansilla-Polo M, Ruiz-Merino G, Marín-Rodríguez P, Iborra-Lacal E, Guzmán-Aroca F. Cavity shaving for invasive breast cancer conservative surgery: Reduced specimen volume and margin positive rates. Surg Oncol. 2021;38:101632. Simpson D, Allan J, McFall B. Radiological Underestimation of Tumor Size Influences the Success Rate of Re-Excision after Breast-conserving Surgery. Eur J Breast Health. 2021;17(4):363–70. Sandor MF, Schwalbach B, Hofmann V, Istrate SE, Schuller Z, Ionescu E, et al. Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscope for intraoperative margin assessment - POLARHIS study. Breast. 2022;66:118–25. Ryan JF, Ghosh S, Rajaee AN, Olson D, Lesniak DM, Peiris LJ. Re-excision rates after breast-conserving surgery for invasive breast cancer: an Albertan perspective. Can J Surg. 2024;67(6):E363–9. Ellbrant J, Gulis K, Plasgård E, Svensjö T, Bendahl PO, Rydén L. Validated prediction model for positive resection margins in breast-conserving surgery based exclusively on preoperative data. BJS Open. 2021;5(5). Romics L, Macaskill EJ, Fernandez T, Simpson L, Morrow E, Pitsinis V, et al. A population-based audit of surgical practice and outcomes of oncoplastic breast conservations in Scotland - An analysis of 589 patients. Eur J Surg Oncol. 2018;44(7):939–44. Abdulla HA, Rajab B, Hammad M, Alrayes A. Risk Factors for Positive Margins in Breast-Conserving Surgery. Cureus. 2023;15(5):e38399. Volders JH, Haloua MH, Krekel NM, Negenborn VL, Barbé E, Sietses C, et al. Neoadjuvant chemotherapy in breast-conserving surgery - Consequences on margin status and excision volumes: A nationwide pathology study. Eur J Surg Oncol. 2016;42(7):986–93. Me A, Akbari M, Zirakzadeh H, Nafissi N, Heidari A, Hosseinizadegan Shirazi F. Margin Status Influence on the Outcome of Patients Treated with Breast Conserving Surgery. Iran J Cancer Prev. 2011;4(4):177–82. Rakha EA, Quinn C, Masannat YA, Lee AHS, Tan PH, Karakatsanis A, et al. Revisiting surgical margins for invasive breast cancer patients treated with breast conservation therapy - Evidence for adopting a 1 mm negative width. Eur J Surg Oncol. 2024;50(10):108573. Bundred JR, Michael S, Stuart B, Cutress RI, Beckmann K, Holleczek B, et al. Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis. BMJ. 2022;378:e070346. Kim Y, Ganduglia-Cazaban C, Tamirisa N, Lucci A, Krause TM. Contemporary Analysis of Reexcision and Conversion to Mastectomy Rates and Associated Healthcare Costs for Women Undergoing Breast-Conserving Surgery. Ann Surg Oncol. 2024;31(6):3649–60. Lamb LR, Mercaldo S, Oseni TO, Bahl M. Predictors of Reexcision following Breast-Conserving Surgery for Ductal Carcinoma In Situ. Ann Surg Oncol. 2021;28(3):1390–7. Valero MG, Mallory MA, Losk K, Tukenmez M, Hwang J, Camuso K, et al. Surgeon Variability and Factors Predicting for Reoperation Following Breast-Conserving Surgery. Ann Surg Oncol. 2018;25(9):2573–8. Krekel N, Zonderhuis B, Muller S, Bril H, van Slooten HJ. de Lange de Klerk E, Excessive resections in breast-conserving surgery: a retrospective multicentre study. Breast J. 2011;17(6):602-9. Tables Table 1. Demographic, clinical, and tumor characteristics of all patients. (n=2586) Mean ± SD/ Number (percentage) Variables 49.11 ± 11.16 Age 27.82 ± 4.70 BMI 26.70 ± 16.92 Tumor Size 1331 (51.9%) 1234 (49.1%) BC Side Left Right 1961 (96.4%) 54 (2.7%) 20 (0.9%) Self- History of cancer None Breast Others 422 (18%) 1287 (55%) 631 (26.9%) Tumor grade G1 G2 G3 1587 (80.8%) 131 (6.7%) 245 (12.5%) Tumor subtype HR+ HER+ TN 1239 (54.2%) 1047 (45.8%) Tumor LVI Positive Negative 2293 (89.0%) 99(3.8%) 183 (7.1%) Tumor histology IDC ILC DCIS 104 (6.9%) 1338 (88.8%) 64 (4.2%) Breast exam findings Normal Mass Other 1022 (42.9%) 1304 (54.7%) 58 (2.4%) Axillary surgery ALND SLND Not 1015(55.4%) 818 (44.6%) Lymph node involvement Yes no (ALN = axillary lymph nodes, ALND = axillary lymph node dissection, BCS = breast-conserving surgery, BC = breast cancer, BMI = body mass index, DCIS = ductal carcinoma in situ, G1 = grade 1, G2 = grade 2, G3 = grade 3, HER+ = positive human epidermal growth factor 2, HR+ = positive hormone receptor, IDC = invasive ductal carcinoma, ILC = invasive lobular carcinoma, LVI = lymphovascular invasion, SLN = sentinel lymph node, SLND = sentinel lymph node dissection, TN = triple negative) Table 2. Effect of Patient- and Tumor-related factors on Margin Involvement Variables Free Margin (n=2305) Involved margin (n=216) P-value Age (yrs) 49.26 ± 11.09 47 ± 11.61 0.005 BMI (kg/m 2 ) 27.81 ± 4.69 27.88 ± 4.81 0.90 Tumor size (mm) 26.15 ± 16.61 31.71 ± 18.37 < 0.001 Lymph node Involvement 2.02 ± 3.60 3.33 ± 6.11 < 0.001 Breast exam findings Normal Mass Others 99 (7.2%) 1230 (88.9%) 55 (4%) 4 (3.5%) 102 (89.5%) 8 (7%) 0.113 Tumor histology IDC ILC DCIS 2071 (89.9%) 82 (3.6%) 150 (6.5%) 175 (81.4%) 15 (7%) 25 (11.6%) 0.001 Grade G1 G2 G3 387 (18.4%) 1150 (54.7%) 566 (26.9%) 31 (16.0%) 111 (57.2%) 52 (26.8%) 0.67 LVI No Yes 989(47.9%) 1075 (52.1%) 46 (24.9%) 139 (75.1%) < 0.001 Subtype HER+ HR+ TN 112 (6.3%) 1450 (81.1%) 225 (12.6%) 14 (9.8%) 116 (81.1%) 13 (9.1%) 0.147 Data are presented as Mean ± standard deviation and number (percentages). BMI = body mass index, DCIS = ductal carcinoma in situ, G1 = grade 1, G2 = grade 2, G3 = grade 3, HER+ = positive human epidermal growth factor 2, HR+ = positive hormone receptor, IDC = invasive ductal carcinoma, ILC = invasive lobular carcinoma, LVI = lymphovascular invasion, TN = triple-negative Table 3. Multivariate analysis of variables Variables Adjusted OR 95%CI P-value Age (yrs) 0.98 0.96-0.99 0.02 T-size (mm) 1.02 1.01-1.03 0.002 Lymphovascular invasion 2.18 1.34-3.53 0.002 Subtype HR+ HER+ TN Ref 1.02 0.62 1 0.47-2.44 0.30-1.28 0.96 0.20 Surgical pathology DCIS IDC ILC Ref 0.90 1.50 1 0.30-2.68 0.41-5.42 0.85 0.54 ALN_ involvement No Yes Ref 1.03 1 0.67-1.59 0.90 ALN= axillary lymph node , DCIS= ductal carcinoma in situ, IDC= = invasive ductal carcinoma, ILC = invasive lobular carcinoma, HER+ = positive human epidermal growth factor 2, HR+ =posetive hormone receptor, TN= triple-negative, T-size= tumor size Additional Declarations No competing interests reported. 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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-6148426","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":447567330,"identity":"6801687a-f6db-4d91-aa51-41e64a5a8c9a","order_by":0,"name":"Sadaf Alipour","email":"","orcid":"","institution":"Breast Diseases Research Center, Cancer Institute, Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Sadaf","middleName":"","lastName":"Alipour","suffix":""},{"id":447567331,"identity":"885b7a7b-f38b-4527-8d2b-a72c84f6bc94","order_by":1,"name":"Bita Eslami","email":"","orcid":"","institution":"Breast Diseases Research Center, Cancer Institute, Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Bita","middleName":"","lastName":"Eslami","suffix":""},{"id":447567332,"identity":"0bbd3b81-88d3-4021-a72c-4659f00f4545","order_by":2,"name":"Nasim Nouri","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Nasim","middleName":"","lastName":"Nouri","suffix":""},{"id":447567333,"identity":"578b5c99-4d6e-4f6c-a503-d079791117e3","order_by":3,"name":"Ramesh Omranipour","email":"","orcid":"","institution":"Department of Cancer Surgery, Cancer Institute, School of Medicine, Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Ramesh","middleName":"","lastName":"Omranipour","suffix":""},{"id":447567334,"identity":"ffc9091c-4c68-4627-b9b1-754e6d583586","order_by":4,"name":"Samareh Heydari","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYLACxgYgcQCIEiqADGbmBhK0PDgD0sJIghbGh21wLm4g33468XPlDpvEvuNnHx5InFcbzd8O1PKjYhtOLQZncjdLnj2TljjzTLrBgcRtx3NnHGZsYOw5cxu3FobcDZKNbYcTNxxIYwBqOZbbANTCzNiGW4t8/9vNPxvb/iduOP8MqGXOsdz5hLQw3MjdBrTlQOKGGyBbGmpyNxDSYnDj7TbLxrZk45k3gLYkHDuQuxGo5SA+v8j3526+2dhmJ9t3Po3544+autx55w8ffPCjAo/DoMCxAUIfBpMHCKoHAnsoXUeM4lEwCkbBKBhhAACKRGzTnEi74AAAAABJRU5ErkJggg==","orcid":"","institution":"Breast Diseases Research Center, Cancer Institute, Tehran University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Samareh","middleName":"","lastName":"Heydari","suffix":""}],"badges":[],"createdAt":"2025-03-03 17:53:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6148426/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6148426/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":81626809,"identity":"81261711-efe7-4bc4-8c6c-08545dfd97f1","added_by":"auto","created_at":"2025-04-29 10:26:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":776495,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6148426/v1/6a8ac9d0-df5d-40b4-8751-a87529d19893.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eFrequency of Positive Margins and Predictors in Breast-Conserving Surgery in developing countries\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eAchieving negative surgical margins besides cosmetic results is a critical determinant of success in breast-conserving surgery (BCS), as positive margins often necessitate re-operation and significantly increase the risk of local recurrence (ranging from 3.5\u0026ndash;6.5%)(\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). While BCS, supported or not by oncoplastic techniques, has become one of the most preferred approaches for breast cancer treatment, especially for early-stage cancer, and aims to achieve oncological safety while preserving breast aesthetics, the rate of positive margins after this type of surgery varies widely across studies, ranging from 10\u0026ndash;38% (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).These variations highlight the effect of factors such as tumor characteristics, institutional practices, and surgical techniques (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Although margin status has been emphasized globally and widely studied, there is a lack of published data about the rate of positive margins following BCS in Iran, creating a gap in understanding the outcomes of this commonly performed procedure in the country.\u003c/p\u003e \u003cp\u003ePrevious studies have shown various factors that impact the likelihood of positive margins. These factors include tumor characteristics, such as histological subtype, size, molecular markers, lymphovascular invasion, and patient-related factors, such as age and body mass index. Additionally, surgical variables, including the type of surgery and surgeon\u0026rsquo;s experiment, have also been reported to impact margin status (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14 CR15 CR16 CR17 CR18\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Despite these insights, there is limited information about how these factors contribute to positive margin rates in Iran.\u003c/p\u003e \u003cp\u003eIn this study, we sought to evaluate the rate of positive margins in BCS cases performed in Iran and investigate the association of the likelihood of positive margins with clinicopathological factors. We aim to enhance surgical practices and patient outcomes in breast cancer treatment by comparing our findings with international data and incorporating surgeons' perspectives during this study.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSettings, Participants, and Eligibility Criteria\u003c/h2\u003e \u003cp\u003eThis retrospective study examined patients with breast cancer who underwent surgery at hospitals affiliated with Tehran University of Medical Sciences from March 2003 to September 2024. The research was approved by the Ethics Committee of TUMS (Approval ID: IR.TUMS.IKHC.REC.1402.229). Written informed consent was obtained from the patients for the use of their data in this study, and the study is conducted under the Declaration of Helsinki. The inclusion criteria consisted of the female sex, breast-conserving surgery (BCS), available demographic, surgical, histological, and molecular data; and availability of contact information. The exclusion criteria encompassed cases of rare breast cancers, such as sarcoma, malignant phyllode tumors, and neuroendocrine carcinoma.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eVariables, Measurements, and Outcomes\u003c/h3\u003e\n\u003cp\u003eEligible patients were identified through a review of medical records and pathology data. Demographic information, including age, body mass index (BMI), clinical findings, relevant imaging results (ultrasonography, mammography, and MRI, when performed), and histological characteristics (tumor type, microscopic features, molecular subtype, tumor size, margin status, type and results of reoperation, and), was extracted. Additionally, information on menopausal status, history of abortion, infertility, blood type, smoking history, hormone therapy, oral contraceptive pill (OCP) use, and family history of breast cancer was collected. Tumor biological characteristics, such as grade, presence and type of metastasis, lymphovascular invasion (LVI), number of positive lymph nodes, hormone receptor status (estrogen receptor (ER), progesterone receptor (PR), and their respective percentages), HER2 status were documented. In cases of incomplete data, follow-up information was obtained by contacting patients or their relatives by phone.\u003c/p\u003e \u003cp\u003eThe relationship between positive surgical margins and various factors, including tumor grade, vascular and lymphatic invasion, lymph node involvement, pathology type, BMI, and was subsequently analyzed.\u003c/p\u003e \u003cp\u003eThe definition of a positive margin has been defined by the Society of Surgical Oncology (SSO) and the American Society for Radiation Oncology (ASTRO)(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eThe analysis for this study was conducted using SPSS version 24 (IBM Corp. 2016. IBM SPSS Statistics for Windows, version 24.0.Armonk, NY: IBM Corp). Quantitative variables were presented as means and standard deviations, while categorical variables were reported as counts and percentages. To compare quantitative variables between the two groups (involved and free margins) a Student T-test was utilized. For qualitative data, the chi-square test was used for comparison. Variables that showed a significance level below 0.05 in the univariate analysis were included in the multivariate logistic regression model. The odds ratio and 95% confidence intervals were calculated to assess the degree of association between the variables and involved margins.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOver the years of our study, 2,585 patients underwent primary BCS in TUMS, with adequate pathology reports for margin status. The mean tumor size was 26.70 ± 16.92 mm, and the mean patient age was 49.11 ± 11.16, ranging from 18 to 88 years.\u0026nbsp;Table 1 details all the patient and tumor characteristics.\u003c/p\u003e\n\u003cp\u003eThe pathological margins were free in 2,305 cases (91.4%), while involved margins were found in 216 patients (8.6%). Among the patients with free margins, 148 had close margins.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEighty-nine percent of cases involved invasive ductal carcinoma. Positive lymphovascular invasion was observed in 1,239 patients (54.2%).\u003c/p\u003e\n\u003cp\u003eAll patients with involved margins underwent a second surgery, which was either a margin re-excision or a mastectomy, depending on the surgeon's recommendation and the patient's preference. There were no additional instances of involved margins after the second surgery.\u003c/p\u003e\n\u003cp\u003eTable 2 shows the relationship between the dependent variable (margin status) and various independent variables, including factors related to patients and tumors.\u003c/p\u003e\n\u003cp\u003eMost patients (89.9%) with invasive ductal carcinoma (IDC) histology exhibited clear pathological margins. There was a significant association between patient age and margin status, indicating that younger patients tend to have more involved margin.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong all the tumor characteristics analyzed, only tumor size, pathology, lymphovascular invasion, and axillary lymph node invasion showed a significant association with margin status in univariate analysis.\u003c/p\u003e\n\u003cp\u003eOf these factors, only tumor size (OR=1.02, 95%CI=1.01-1.03), lymphovascular invasion (OR=2.18, 95%CI=1.34-3.53), and patient age (OR=0.98, 95%CI= 0.96-0.99) remain significantly associated with margin involvement after multivariate analysis.\u003c/p\u003e\n\u003cp\u003eOver the past 20 years, we observed a significant improvement in margin status, with a p-value of less than 0.001. The free margin increased from 0.6% reported in 2003 to 4.8% among 2024 patients.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe current study found a positive margin rate of about 9% in Iran. We also analyzed patient outcomes and discovered that larger tumor sizes and younger ages are associated with involved margins after breast-conserving surgery (BCS), which is consistent with previous studies (\u003cspan additionalcitationids=\"CR22 CR23 CR24 CR25\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Additionally, we identified lymphovascular invasion as a significant predictor of margin involvement.\u003c/p\u003e \u003cp\u003eSince the involvement of surgical margins after breast-conserving surgery (BCS) is a significant predictor of local recurrence of the disease, failing to achieve negative margins often necessitates further surgery, such as re-excision or mastectomy(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Second surgeries raise costs for the health care system and the patients and may lead to larger post-surgical defects, worsening aesthetic outcomes, and delaying necessary adjuvant therapy (\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eReoperation rates after BCS vary significantly between centers and institutions (\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Each center should evaluate its performance metrics to determine effectiveness and identify areas for improvement. Also, identifying patient and tumor characteristics associated with involved margins before surgery would enhance patient counseling and assist the surgeon in making preoperative decisions before the first procedure.\u003c/p\u003e \u003cp\u003eThe 9% rate of margin positivity reported in the current study is lower than rates published by other centers, including a rate of 24% in Bahrain (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e),11% in Canada (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), around 66% in Italy (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), and 25% in the Netherlands (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). The difference may stem from several factors. To evaluate the point of view of surgeons in our country regarding the rate of BCS positive margins in Iran in comparison with literature reports and also the reasons for any difference in their opinion, we surveyed 30 active breast surgeons using two dedicated multiple-choice questions asking exactly these two questions. The survey showed that most surgeons believed the margin involvement rate in Iran is lower than that in Western studies, and most attributed this to larger tissue resection during initial surgeries, as patients are strongly reluctant to undergo re-operations. This is probably true, and the most likely reason for a low margin-positivity is because of the initial wide margin excision due to patients' unacceptance of further excision. Other factors that can be mentioned include the high costs of radiotherapy and chemotherapy and the possibility of needing further treatments due to close margins. Baliski et al.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) study supports these findings, showing that a larger CRR (calculated resection ratio) is more indicative of free margins.\u003c/p\u003e \u003cp\u003eIt is important to highlight that a previous study by Akbari et al. in Iran (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e) found a positive margin rate of 1\u0026ndash;2%. The difference in our findings and the more reasonable and expectable rate in our study might be because of the higher sample size, and the multicentric nature of our study.\u003c/p\u003e \u003cp\u003eThe definition of margin status has changed over the years. Before the SSO-ASTRO introduced \"no ink on the tumor\" in 2014, surgeons had varied and conservative methods for assessing margins. A 1995 study, for example, defined a close margin as being 12 mm from the tumor edge(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRecent studies have suggested that the definition of a negative margin in the context of BCS should be reconsidered (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). Additionally, it has been noted that the rates of reoperation after BCS remain high (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e), indicating a continuing need for quality improvement in this area. This could be addressed by enhancing intraoperative margin assessment techniques, using options like shaving cavity margins (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e), or identifying predictors that contribute to an increased re-excision rate, which was done during this study.\u003c/p\u003e \u003cp\u003eOur analyses indicated an improvement in the re-excision rate during the recent 20 years. This finding has occurred in many centers globally and is partly due to the change in guidelines and margin definitions, as shown in a meta-analysis by Marinovichet et al. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) in 2020.\u003c/p\u003e \u003cp\u003eThe current study identifies tumor size and lymphovascular invasion as significant factors that correlate with positive margins. It indicates that larger tumors with positive lymphovascular invasion are at a higher risk of having pathologically positive margins. Previous studies have also shown that larger tumors tend to have more positive margins, (\u003cspan additionalcitationids=\"CR22 CR23 CR24 CR25\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e) possibly due to the challenges of removing a large tumor while also considering cosmetic outcomes.\u003c/p\u003e \u003cp\u003eLymphovascular invasion has not been as frequently discussed as a predictor of margin status in studies compared to tumor size. However, Deurzan et al.'s multivariate analysis (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) demonstrates a significant association between positive angioinvasion and positive margins.\u003c/p\u003e \u003cp\u003eIn this study, the patient's age is also identified as a predictor of margin involvement, supporting previous data showing higher positive margins after initial BCS in younger patients(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e), particularly those under 40 (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e), under 46 (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), or between 45 and 60 years old (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Denser breast tissue in younger patients may lead to less accurate tumor size assessments before surgery. Additionally, younger patients often prioritize cosmetic outcomes, resulting in smaller excisions that can cause a higher rate of positive margins and require further surgery.\u003c/p\u003e \u003cp\u003eILC and DCIS were more often associated with involved margins, suggesting that these histologic subtypes may increase the likelihood of having involved margins, similar to the study of Ellbrant et al. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Still, it wasn\u0026rsquo;t statistically significant during our study. This is in contrast to a study by Krekel et al.(\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e), who reported a lower positive margin rate for nonpalpable lesions, including DCIS. Furthermore, another study found no significant differences in margin status between palpable and nonpalpable tumors(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Nonetheless, mass formation is more common in IDC tumors, whereas DCIS or ILC may not present with obvious masses; this may explain the improved understanding of the cancer boundaries and limits by surgeons, leading to better margin resection in IDC. There is a slight increase in margin positivity among HER\u0026thinsp;+\u0026thinsp;patients, but this result was not statistically significant, possibly due to the smaller number of HER\u0026thinsp;+\u0026thinsp;patients compared to HR\u0026thinsp;+\u0026thinsp;patients.\u003c/p\u003e \u003cp\u003eIn general, our study aligns with Zavagno et al.'s findings(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) regarding predictor factors, but it differs in the margin status rate. This indicates an improvement in BCS management over the years.\u003c/p\u003e \u003cp\u003eUnderstanding the factors contributing to ineffectiveness can be beneficial. In Iran, the lack of national BC screening programs has led to the late detection of tumors, resulting in most tumors being palpable during initial physical examinations. Therefore, this study did not recognize a palpable tumor in the first physical examination as a predictor of margin status despite previous studies in other countries.\u003c/p\u003e \u003cp\u003eThis study had some limitations. The data was collected from University-affiliated hospitals in Tehran, which may not represent practice in all regions of Iran. Also, considering the retrospective nature of this study, incomplete data from earlier years may have influenced certain clinical variables, although efforts were made to supplement this information. It should be noted that this study provides the first comprehensive evaluation of positive margin rates in BCS in Iran and highlights the key factors contributing to margin status.\u003c/p\u003e \u003cp\u003eFuture prospective studies conducted across a broader range of hospitals in Iran, incorporating advanced intraoperative margin assessment tools, could help address these limitations.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this study, we identified a lower margin positivity rate in BCS compared with studies from other countries. According to experts, this lower rate might be due to patients' unacceptance of reoperation. Also, various clinical and pathological factors significantly linked to involved resection margins were considered. Since most of these factors can be evaluated preoperatively, this presents an opportunity for improved risk prediction before surgery and potential adjustments to the surgical approach.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBCS, BCT, BMI, LVI, ER, PR, HER2, OCP, IDC, ILC, DCIS, CRR\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e The research was approved by the Ethics Committee of TUMS (Approval ID: \u0026nbsp;IR.TUMS.IKHC.REC.1402.229). The patients gave written informed consent for using their data in this study, which was conducted according to the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u0026nbsp;\u003c/strong\u003eSadaf Alipour, Ramesh Omranipour, and Bita Eslami contributed to the study conception and design. Material preparation and data collection were performed by Samareh Heydari and Nasim Nouri. Statistical analysis was conducted by Bita Eslami. The first draft of the manuscript was written by Samareh Heydari and Nasim Nouri. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003e\u0026nbsp; We would like to acknowledge Drs. Negar Mashoori,\u003c/p\u003e\n\u003cp\u003eAdel Yazadnkhah Kenary, Mandana Motamedi, Mahsa Tavakol, Maryam Sarkardeh, Ms. Mahta Mohammadzadeh, Shiller Hessamiazar, Samira Shabani, Fatemeh Mahmoodi, and Mr. Mohammadreza Mirzaee Goodarzi for their assistance in gathering the proper data. We also acknowledge the Deputy of Research of Tehran University of Medical Sciences for their financial support of the project.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBaliski C, Hughes L, Bakos B. Lowering Re-excision Rates After Breast-Conserving Surgery: Unraveling the Intersection Between Surgeon Case Volumes and Techniques. Ann Surg Oncol. 2021;28(2):894\u0026ndash;901.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTamburelli F, Maggiorotto F, Marchi\u0026ograve; C, Balmativola D, Magistris A, Kubatzki F, et al. Reoperation rate after breast conserving surgery as quality indicator in breast cancer treatment: A reappraisal. Breast. 2020;53:181\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLandercasper J, Borgert AJ, Fayanju OM, Cody H 3rd, Feldman S, Greenberg C, et al. Factors Associated with Reoperation in Breast-Conserving Surgery for Cancer: A Prospective Study of American Society of Breast Surgeon Members. Ann Surg Oncol. 2019;26(10):3321\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAnderson SJ, Wapnir I, Dignam JJ, Fisher B, Mamounas EP, Jeong JH, et al. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative breast cancer. J Clin Oncol. 2009;27(15):2466\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZavagno G, Goldin E, Mencarelli R, Capitanio G, Del Bianco P, Marconato R, et al. Role of resection margins in patients treated with breast conservation surgery. Cancer. 2008;112(9):1923\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarinovich ML, Noguchi N, Morrow M, Houssami N. Changes in Reoperation After Publication of Consensus Guidelines on Margins for Breast-Conserving Surgery: A Systematic Review and Meta-analysis. JAMA Surg. 2020;155(10):e203025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAziz D, Rawlinson E, Narod SA, Sun P, Lickley HL, McCready DR, et al. The role of reexcision for positive margins in optimizing local disease control after breast-conserving surgery for cancer. Breast J. 2006;12(4):331\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKurniawan ED, Wong MH, Windle I, Rose A, Mou A, Buchanan M, et al. Predictors of surgical margin status in breast-conserving surgery within a breast screening program. Ann Surg Oncol. 2008;15(9):2542\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaloua MH, Volders JH, Krekel NM, Barb\u0026eacute; E, Sietses C, J\u0026oacute;źwiak K, et al. A nationwide pathology study on surgical margins and excision volumes after breast-conserving surgery: There is still much to be gained. Breast. 2016;25:14\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRubio IT, Ahmed M, Kovacs T, Marco V. Margins in breast conserving surgery: A practice-changing process. Eur J Surg Oncol. 2016;42(5):631\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJung W, Kang E, Kim SM, Kim D, Hwang Y, Sun Y, et al. Factors Associated with Re-excision after Breast-Conserving Surgery for Early-Stage Breast Cancer. J Breast Cancer. 2012;15(4):412\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRossou C, Alampritis G, Patel B. Reducing re-excision rates in breast conserving surgery with Margin Probe: systematic review. Br J Surg. 2024;111(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTouboul E, Buffat L, Belkac\u0026eacute;mi Y, Lefranc JP, Uzan S, Lhuillier P, et al. Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer. Int J Radiat Oncol Biol Phys. 1999;43(1):25\u0026ndash;38.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSrour MK, Manguso N, Mirocha J, Chung A, Giuliano AE, Amersi F. Impact of Resident and Fellow Participation on Surgical Outcomes in Breast Conserving Surgery for Invasive Breast Cancer. J Surg Educ. 2020;77(1):144\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheun JH, Lee YJ, Lee JH, Shin Y, Chun JW, Baek SY, et al. Surgical margin status and survival outcomes of breast cancer patients treated with breast-conserving surgery and whole-breast irradiation after neoadjuvant chemotherapy. Breast Cancer Res Treat. 2022;194(3):683\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoran MS, Schnitt SJ, Giuliano AE, Harris JR, Khan SA, Horton J, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. J Clin Oncol. 2014;32(14):1507\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoussami N, Macaskill P, Marinovich ML, Dixon JM, Irwig L, Brennan ME, et al. Meta-analysis of the impact of surgical margins on local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy. Eur J Cancer. 2010;46(18):3219\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChakedis JM, Chang SB, Tang A, Kuehner GE, Savitz AC, Vuong B, et al. Assessment of Surgeon Factors Associated With Margin Re-excision After Breast-Conserving Surgery. JAMA Netw Open. 2022;5(8):e2228100.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBiglia N, Ponzone R, Bounous VE, Mariani LL, Maggiorotto F, Benevelli C, et al. Role of re-excision for positive and close resection margins in patients treated with breast-conserving surgery. Breast. 2014;23(6):870\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorrow M, Van Zee KJ, Solin LJ, Houssami N, Chavez-MacGregor M, Harris JR, et al. Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma In Situ. J Clin Oncol. 2016;34(33):4040\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFisher S, Yasui Y, Dabbs K, Winget M. Re-excision and survival following breast conserving surgery in early stage breast cancer patients: a population-based study. BMC Health Serv Res. 2018;18(1):94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBouz\u0026oacute;n A, Acea B, Garc\u0026iacute;a A, Iglesias \u0026Aacute;, Mosquera J, Santiago P, et al. Risk factors for positive margins in conservative surgery for breast cancer after neoadjuvant chemotherapy. Cir Esp. 2016;94(7):379\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHughes L, Hamm J, McGahan C, Baliski C. Surgeon Volume, Patient Age, and Tumor-Related Factors Influence the Need for Re-Excision After Breast-Conserving Surgery. Ann Surg Oncol. 2016;23(Suppl 5):656\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFauveau LR, Dao TN, Wallace LB, Mamawala MK, Obaid A, Waddimba AC, et al. Positive surgical margins after breast-conserving surgery for ductal carcinoma in-situ: does histologic grade or estrogen receptor status matter? Breast Cancer Res Treat. 2023;199(2):215\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Deurzen CH. Predictors of Surgical Margin Following Breast-Conserving Surgery: A Large Population-Based Cohort Study. Ann Surg Oncol. 2016;23(Suppl 5):627\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDhak S, Baliski C, Bakos B. Factors influencing suboptimal pathologic margins and re-excision following breast conserving surgery for ductal carcinoma in-situ. Am J Surg. 2023;225(5):866\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmitt MC, Nowels KW, Zdeblick MJ, Jeffrey S, Carlson RW, Stockdale FE, et al. The importance of the lumpectomy surgical margin status in long-term results of breast conservation. Cancer. 1995;76(2):259\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMansilla-Polo M, Ruiz-Merino G, Mar\u0026iacute;n-Rodr\u0026iacute;guez P, Iborra-Lacal E, Guzm\u0026aacute;n-Aroca F. Cavity shaving for invasive breast cancer conservative surgery: Reduced specimen volume and margin positive rates. Surg Oncol. 2021;38:101632.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimpson D, Allan J, McFall B. Radiological Underestimation of Tumor Size Influences the Success Rate of Re-Excision after Breast-conserving Surgery. Eur J Breast Health. 2021;17(4):363\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSandor MF, Schwalbach B, Hofmann V, Istrate SE, Schuller Z, Ionescu E, et al. Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscope for intraoperative margin assessment - POLARHIS study. Breast. 2022;66:118\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRyan JF, Ghosh S, Rajaee AN, Olson D, Lesniak DM, Peiris LJ. Re-excision rates after breast-conserving surgery for invasive breast cancer: an Albertan perspective. Can J Surg. 2024;67(6):E363\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEllbrant J, Gulis K, Plasg\u0026aring;rd E, Svensj\u0026ouml; T, Bendahl PO, Ryd\u0026eacute;n L. Validated prediction model for positive resection margins in breast-conserving surgery based exclusively on preoperative data. BJS Open. 2021;5(5).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRomics L, Macaskill EJ, Fernandez T, Simpson L, Morrow E, Pitsinis V, et al. A population-based audit of surgical practice and outcomes of oncoplastic breast conservations in Scotland - An analysis of 589 patients. Eur J Surg Oncol. 2018;44(7):939\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbdulla HA, Rajab B, Hammad M, Alrayes A. Risk Factors for Positive Margins in Breast-Conserving Surgery. Cureus. 2023;15(5):e38399.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVolders JH, Haloua MH, Krekel NM, Negenborn VL, Barb\u0026eacute; E, Sietses C, et al. Neoadjuvant chemotherapy in breast-conserving surgery - Consequences on margin status and excision volumes: A nationwide pathology study. Eur J Surg Oncol. 2016;42(7):986\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMe A, Akbari M, Zirakzadeh H, Nafissi N, Heidari A, Hosseinizadegan Shirazi F. Margin Status Influence on the Outcome of Patients Treated with Breast Conserving Surgery. Iran J Cancer Prev. 2011;4(4):177\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRakha EA, Quinn C, Masannat YA, Lee AHS, Tan PH, Karakatsanis A, et al. Revisiting surgical margins for invasive breast cancer patients treated with breast conservation therapy - Evidence for adopting a 1 mm negative width. Eur J Surg Oncol. 2024;50(10):108573.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBundred JR, Michael S, Stuart B, Cutress RI, Beckmann K, Holleczek B, et al. Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis. BMJ. 2022;378:e070346.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim Y, Ganduglia-Cazaban C, Tamirisa N, Lucci A, Krause TM. Contemporary Analysis of Reexcision and Conversion to Mastectomy Rates and Associated Healthcare Costs for Women Undergoing Breast-Conserving Surgery. Ann Surg Oncol. 2024;31(6):3649\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLamb LR, Mercaldo S, Oseni TO, Bahl M. Predictors of Reexcision following Breast-Conserving Surgery for Ductal Carcinoma In Situ. Ann Surg Oncol. 2021;28(3):1390\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValero MG, Mallory MA, Losk K, Tukenmez M, Hwang J, Camuso K, et al. Surgeon Variability and Factors Predicting for Reoperation Following Breast-Conserving Surgery. Ann Surg Oncol. 2018;25(9):2573\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrekel N, Zonderhuis B, Muller S, Bril H, van Slooten HJ. de Lange de Klerk E, Excessive resections in breast-conserving surgery: a retrospective multicentre study. Breast J. 2011;17(6):602-9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Demographic, clinical, and tumor characteristics of all patients. (n=2586)\u003c/p\u003e\n\u003cdiv align=\"left\"\u003e\n \u003ctable dir=\"rtl\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"323\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eMean \u0026plusmn; SD/\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eNumber (percentage)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp dir=\"LTR\"\u003e49.11 \u0026plusmn; 11.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp dir=\"LTR\"\u003e27.82 \u0026plusmn; 4.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eBMI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp dir=\"LTR\"\u003e26.70 \u0026plusmn; 16.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eTumor Size\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e1331 (51.9%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e1234 (49.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eBC Side\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eLeft\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e1961 (96.4%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e54 (2.7%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e20 (0.9%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eSelf- History of cancer\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eNone\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eBreast\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e422 (18%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e1287 (55%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e631 (26.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eTumor grade\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eG1\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eG2\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eG3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e1587 (80.8%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e131 (6.7%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e245 (12.5%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eTumor subtype\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eHR+\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eHER+\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eTN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e1239 (54.2%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e1047 (45.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eTumor LVI\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003ePositive\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e2293 (89.0%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e99(3.8%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e183 (7.1%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eTumor histology\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eIDC\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eILC\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eDCIS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e104 (6.9%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e1338 (88.8%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e64 (4.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eBreast exam findings\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eNormal\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eMass\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e1022 (42.9%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e1304 (54.7%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e58 (2.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eAxillary surgery\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eALND\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eSLND\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eNot\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e1015(55.4%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e818 (44.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eLymph node involvement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eYes\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e(ALN = axillary lymph nodes, ALND = axillary lymph node dissection, BCS = breast-conserving surgery, BC = breast cancer, BMI = body mass index, DCIS = ductal carcinoma in situ, G1 = grade 1, G2 = grade 2, G3 = grade 3, HER+ = positive human epidermal growth factor 2, HR+ = positive hormone receptor, IDC = invasive ductal carcinoma, ILC = invasive lobular carcinoma, LVI = lymphovascular invasion, SLN = sentinel lymph node, SLND = sentinel lymph node dissection, TN = triple negative)\u003c/p\u003e\n\u003cp\u003eTable 2. Effect of Patient- and Tumor-related factors on Margin Involvement\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"487\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 181px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFree Margin\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=2305)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInvolved margin\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=216)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 181px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u0026nbsp;\u003c/strong\u003e(yrs)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e49.26 \u0026plusmn; 11.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e47 \u0026plusmn; 11.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 181px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI\u0026nbsp;\u003c/strong\u003e(kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e27.81 \u0026plusmn; 4.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e27.88 \u0026plusmn; 4.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 181px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor size\u0026nbsp;\u003c/strong\u003e(mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e26.15 \u0026plusmn; 16.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e31.71 \u0026plusmn; 18.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 181px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLymph node Involvement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e2.02 \u0026plusmn; 3.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e3.33 \u0026plusmn; 6.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 181px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBreast exam\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e findings\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNormal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMass\u003c/p\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e99 (7.2%)\u003c/p\u003e\n \u003cp\u003e1230 (88.9%)\u003c/p\u003e\n \u003cp\u003e55 (4%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (3.5%)\u003c/p\u003e\n \u003cp\u003e102 (89.5%)\u003c/p\u003e\n \u003cp\u003e8 (7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.113\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 181px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor histology\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eIDC\u003c/p\u003e\n \u003cp\u003eILC\u003c/p\u003e\n \u003cp\u003eDCIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2071 (89.9%)\u003c/p\u003e\n \u003cp\u003e82 (3.6%)\u003c/p\u003e\n \u003cp\u003e150 (6.5%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e175 (81.4%)\u003c/p\u003e\n \u003cp\u003e15 (7%)\u003c/p\u003e\n \u003cp\u003e25 (11.6%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 181px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eG1\u003c/p\u003e\n \u003cp\u003eG2\u003c/p\u003e\n \u003cp\u003eG3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e387 (18.4%)\u003c/p\u003e\n \u003cp\u003e1150 (54.7%)\u003c/p\u003e\n \u003cp\u003e566 (26.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31 (16.0%)\u003c/p\u003e\n \u003cp\u003e111 (57.2%)\u003c/p\u003e\n \u003cp\u003e52 (26.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 181px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLVI\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e989(47.9%)\u003c/p\u003e\n \u003cp\u003e1075 (52.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e46 (24.9%)\u003c/p\u003e\n \u003cp\u003e139 (75.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 181px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSubtype\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eHER+\u003c/p\u003e\n \u003cp\u003eHR+\u003c/p\u003e\n \u003cp\u003eTN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e112 (6.3%)\u003c/p\u003e\n \u003cp\u003e1450 (81.1%)\u003c/p\u003e\n \u003cp\u003e225 (12.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 (9.8%)\u003c/p\u003e\n \u003cp\u003e116 (81.1%)\u003c/p\u003e\n \u003cp\u003e13 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.147\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are presented as Mean \u0026plusmn; standard deviation and number (percentages).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;BMI = body mass index, DCIS = ductal carcinoma in situ, G1 = grade 1, G2 = grade 2, G3 = grade 3, HER+ = positive human epidermal growth factor 2, HR+ = positive hormone receptor, IDC = invasive ductal carcinoma, ILC = invasive lobular carcinoma, LVI = lymphovascular invasion, TN = triple-negative\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3. Multivariate analysis of variables\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"463\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted OR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95%CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (yrs)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e0.96-0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.02\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT-size (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e1.01-1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLymphovascular invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e2.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e1.34-3.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSubtype\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eHR+\u003c/p\u003e\n \u003cp\u003eHER+\u003c/p\u003e\n \u003cp\u003eTN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e1.02\u003c/p\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e0.47-2.44\u003c/p\u003e\n \u003cp\u003e0.30-1.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgical pathology\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eDCIS\u003c/p\u003e\n \u003cp\u003eIDC\u003c/p\u003e\n \u003cp\u003eILC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.90\u003c/p\u003e\n \u003cp\u003e1.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e0.30-2.68\u003c/p\u003e\n \u003cp\u003e0.41-5.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALN_ involvement\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e0.67-1.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eALN= axillary lymph node , DCIS= ductal carcinoma in situ, IDC= = invasive ductal carcinoma, ILC = invasive lobular carcinoma, HER+ = positive human epidermal growth factor 2, HR+ =posetive hormone receptor, TN= triple-negative, T-size= tumor size\u003c/p\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":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Breast cancer, Breast-conserving therapy, (BCT), Positive surgical margin, Re-operation, Risk factors ","lastPublishedDoi":"10.21203/rs.3.rs-6148426/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6148426/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e Achieving negative surgical margins in breast-conserving surgery (BCS) is crucial due to the risks linked to positive margins, such as the need for reoperation and elevated local recurrence rates. Limited data exist about positive margins after BCS in developing countries, including Iran, and this study aims to close this gap by assessing the rates of positive margins in BCS and the factors that affect it.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod \u0026nbsp;\u003c/strong\u003eThis retrospective study investigated breast cancer patients at Tehran University of Medical Sciences from 2003 to 2024. It included female patients who underwent breast-conserving surgery (BCS) and had complete data available. The rate of positive margins in histological assessment of surgical specimens and its relationship with various tumor and patient factors were explored using univariate and multivariate logistic model analyses.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResult\u003c/strong\u003e A total of 2,585 patients underwent BCS, with a median age of 49 and a mean tumor size of 27 mm. Free surgical margins were found in 91.4% of cases, while 8.6% exhibited involved margins, these underwent re-excision of the involved margin. A significant association was observed between younger patient age, tumor size, lymphovascular invasion, and margin involvement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e \u0026nbsp;This study found a lower margin positivity rate in BCS than reported in the great part of the present literature, it also identified preoperative clinical and pathological factors linked to margin involvement, allowing for better risk prediction and potential surgical adjustments.\u003c/p\u003e","manuscriptTitle":"Frequency of Positive Margins and Predictors in Breast-Conserving Surgery in developing countries","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-29 10:10:33","doi":"10.21203/rs.3.rs-6148426/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-28T10:56:39+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-04T06:31:47+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-19T07:05:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"259706402426563096116593177220759305032","date":"2025-04-16T22:23:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-16T14:14:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"320419986386788533192874450272114480693","date":"2025-04-16T06:29:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"73398269297858139672893746841730841015","date":"2025-04-14T15:46:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-14T15:17:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-09T14:26:03+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-03-17T04:23:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-14T11:54:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-03-14T11:53:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c700ed35-f17a-4d5c-9601-76089f26a53e","owner":[],"postedDate":"April 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-07-14T09:53:19+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-29 10:10:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6148426","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6148426","identity":"rs-6148426","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
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