pISSN 1738-6756   eISSN 2092-9900
Open Access, Peer-reviewed
    J Breast Cancer. 2023 Dec;26(6):558-571. English.
    Published online Oct 17, 2023.
    https://doi.org/10.4048/jbc.2023.26.e46
    © 2023 Korean Breast Cancer Society
    Original Article

    Residual Risk of Ipsilateral Tumor Recurrence in Patients Who Achieved Clear Lumpectomy Margins After Repeated Resection

    Jong-Ho Cheun,1,* Hong-Kyu Kim,1,2 Han-Byoel Lee,1,2,3 Wonshik Han,1,2,3 and Hyeong-Gon Moon1,2,3
      • 1Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
      • 2Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
      • 3Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
    • Correspondence to Hyeong-Gon Moon. Department of Surgery, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea. Email: moonhg74@snu.ac.kr
      *Present address: Department of Surgery, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
    Received March 31, 2023; Revised August 15, 2023; Accepted September 18, 2023.

    This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Abstract

    Purpose

    Patients with breast cancer with positive lumpectomy margins have a two-fold increased risk of ipsilateral breast tumor recurrence (IBTR). This can be the result of either technically incomplete resection or the biological characteristics of the tumor that lead to a positive margin. We hypothesized that if achieving negative margins by re-excision nullifies the IBTR risk, then the increased risk is mainly attributed to the technical incompleteness of the initial surgeries. Thus, we investigated IBTR rates in patients with breast cancer who achieved clear margins after re-excision.

    Methods

    We retrospectively reviewed patients who underwent breast lumpectomy for invasive breast cancer between 2004 and 2018 at a single institution, and investigated IBTR events.

    Results

    Among 5,598 patients, 793 achieved clear margins after re-excision of their initial positive margins. During the median follow-up period of 76.4 months, 121 (2.2%) patients experienced IBTR. Patients who underwent re-excision to achieve negative margin experienced significantly higher IBTR rates compared to those achieving clear margin at first lumpectomy (10-year IBTR rate: 5.3% vs. 2.6% [25 vs. 84 events]; unadjusted p = 0.031, hazard ratio, 1.61, 95% confidence interval [CI], 1.04–2.48; adjusted p = 0.030, hazard ratio, 1.69, 95% CI, 1.05–2.72). This difference was more evident in patients aged < 50 years and those with delayed IBTR. Additionally, no statistically significant differences were observed in the spatial distribution of IBTR locations.

    Conclusion

    Patients who underwent re-excision for initial positive margins had an increased risk of IBTR, even after achieving a final negative margin, compared to patients with negative margins initially. This increased risk of IBTR is mostly observed in young patients and delayed cases.

    Keywords
    Breast Neoplasms; Margins of Excision; Neoplasm Recurrence, Local

    INTRODUCTION

    Currently, the widely accepted principle guiding lumpectomy margins in early breast cancer patients is to avoid the presence of tumor cells at the margin (‘no ink on tumor’). The ‘no ink on tumor’ principle was based on the results of a meta-analysis involving 28,162 patients in 33 studies, which demonstrated a lack of benefit in achieving a wide resection margin once the margin was free of tumor cells [1]. The introduction of the ‘no ink on tumor’ principle and the subsequent endorsement by academic societies has substantially reduced the rate of re-excision after initial lumpectomy [2, 3].

    However, more than 15% of patients who were initially treated with lumpectomy still underwent additional surgery [3, 4], and 8.5% of patients with positive resection margins chose mastectomy as their next procedure [5]. Although the potential disadvantages of reoperations, such as increased emotional stress, deterioration of cosmesis [6], and increased healthcare costs [7], are well known, most patients with positive margins undergo re-excision to minimize the risk of ipsilateral breast tumor recurrence (IBTR). Moreover, studies have repeatedly indicated a two-fold increased risk of IBTR with positive resection margins [1, 8].

    The presence of tumor cells at the lumpectomy margin represents two different aspects of local control in breast cancer. One aspect is related to potential technical failure, which may lead to incomplete tumor resection [9, 10]. Another aspect of a positive margin is the biological nature of the tumor. For example, extensive intraductal tumor components often result in positive lumpectomy margins [11] and may lead to an increased risk of local recurrence after breast conservation surgery [12]. Additionally, lobular histology is associated with margin positivity [13, 14] and an increased risk of IBTR [15]. Therefore, the two-fold increase in IBTR risk with positive margins reflects the combined effect of both technical failure and biological characteristics.

    In this study, we aimed to address this issue by investigating the IBTR rates in patients who achieved negative margins through initial lumpectomy or re-excision. We assumed that if the IBTR rates of the two groups are comparable, then the two-fold increase in IBTR risk associated with a positive margin is mostly caused by technically incomplete resections, as achieving negative margins by repeated excision nullifies the IBTR risk.

    METHODS

    This study was approved by the Institutional Review Board (IRB) of Seoul National University Hospital (IRB No. H2109-125-1257) and was performed in accordance with the Declaration of Helsinki or comparable ethical standards. The requirement for informed consent was waived; however, the reuse of their electronically recorded data was approved.

    Study design

    We retrospectively reviewed the data of patients with invasive breast cancer who underwent upfront breast conservation surgery followed by whole-breast irradiation between January 2004 and December 2018 at Seoul National University Hospital. Patients who received neoadjuvant chemotherapy and those with male breast cancer, bilateral breast cancer, recurrent breast cancer, or stage IV breast cancer were excluded. A clear resection margin was defined as “no ink on tumor.” Focusing on the IBTR, patients who underwent a mastectomy to achieve a clear resection margin after breast-conserving surgery were also excluded from the analysis.

    Breast cancer was pathologically staged according to the 8th American Joint Committee on Cancer staging criteria. Hormone receptor (HR) status, including estrogen and progesterone receptors, was reported to be positive when dyed at > 1% on immunohistochemistry. Human epidermal growth factor receptor-2 (HER2) status was assessed using anti-HER2 antibodies and/or fluorescence in situ hybridization.

    Regarding radiation treatment, patients received radiation treatment with a regimen of either conventional fractionated 1.8–2.0 gray in 28–33 fractions over 6 weeks or hypofractionated 2.4–2.7 gray in 15–20 fractions over 3 weeks, once daily according to the fractionation schedule of our institution. An additional boost to the tumor bed was applied, depending on the clinical experience of the radiation oncologists. Patients who discontinued radiation treatment for various reasons were excluded from the study.

    Evaluation of resection margin status

    The extent of surgical resection was determined based on the extent of the disease on magnetic resonance imaging or sonography. Cavity shaving or intraoperative frozen-section biopsy for the resection margin was not routinely conducted in all patients, and the decision to do so was made by the surgeon. Furthermore, separate cavity shaving was performed in the direction of the residual parenchyma after resection of the main tumor with or without intraoperative frozen biopsy. The outer surface of the resected specimen was sutured.

    When a frozen-section biopsy revealed the involvement of atypical or tumor cells on the resection margin, additional tissue excision was performed in the direction of the positive margin. As further resected tissue is usually sutured and attached to the main specimen, pathologists examine the specimen as a whole and not as separate specimens. In contrast, when tumor cells were identified in lumpectomy margins via the final pathology reports 1 or 2 weeks after surgery, we conducted reoperation, and a separate pathology review for the additionally resected tissues was obtained separately.

    Definition of IBTR and recurrence-free survival

    The recurrence of breast cancer in the ipsilateral breast was defined as IBTR; however, recurrence in the breast skin was not included in the IBTR. Other types of recurrences, including regional recurrence or distant metastasis before IBTR, were treated as censored events related to competing risks. The IBTR-free survival rate was calculated as the interval from the date of the last surgery to the time of pathological diagnosis of IBTR or censored events.

    Statistical analysis

    The continuous variables were compared with one-way analysis of variance and categorical variables were compared with Pearson’s χ2 test. The log-rank test was used to analyze the differences between the survival curves derived using the Kaplan-Meier method. A Cox proportional hazards regression model was used to estimate the adjusted hazard ratio and to adjust for other variables affecting the recurrence rate. Statistical significance was set at p < 0.05. All analyses were performed using SPSS (version 26.0; IBM, Armonk, USA), and figures were plotted using GraphPad Prism (version 9.0; GraphPad Software, San Diego, USA). Propensity score matching was conducted using the “MatchIt” R package (version 3.6.3; R Foundation, Vienna, Austria).

    RESULTS

    Patient characteristics

    Between January 2004 and December 2018, 5,632 patients underwent breast conservation surgery and breast radiation therapy at our institution. During the study period, 34 patients (0.6%) had positive resection margins and did not undergo additional surgery for various reasons, including comorbidities or patient refusal. The aforementioned 34 patients had a significantly higher risk of IBTR compared to the remaining patients with clear final resection margins (10-year IBTR rate: 17.8% vs. 3.0%; p < 0.001, hazard ratio, 7.56, 95% confidence interval [CI], 3.09–18.51, Supplementary Figure 1). As we aimed to compare the IBTR rates among patients with clear final resection margins based on re-excision, the remaining 5,598 patients were the main participants of this study.

    Among the 5,598 patients, 793 (14.2%) achieved clear margins after re-excision because of their positive resection margins. The median age of the patients was 49 years old (19–92), and nearly two-thirds had T1 tumors (64.3%). A total of 4,293 patients (76.7%) were node-negative, and 4,332 (77.4%) had HR-positive tumors. Intraoperative margin assessment was performed in 4,098 (73.2%). Detailed information on the study population is presented in Table 1.

    Table 1
    Demographics and clinicopathologic characteristics of patients who achieved clear resection margin

    Impact of re-excision on the risk of IBTR

    During the median follow-up period of 76.6 (± 44.6) months, a total of 121 patients (2.2%) experienced IBTR. Additionally, 95 patients achieved clear resection margin at first lumpectomy and 26 patients underwent re-excision. Patients who underwent re-excision to achieve negative margins experienced a significantly higher rate of IBTR compared to patients in whom the margins were clear at the first lumpectomy (10-year IBTR rate: 5.3% vs. 2.6% [25 vs. 84 events], p = 0.031; hazard ratio, 1.61; 95% CI, 1.04–2.48) (Figure 1A). The survival curves began to separate around 4–5 years after surgery (98.5% vs. 98.0% [64 vs. 14 events] at 5 years, and 97.4% vs. 94.7% at 10 years of follow-up). Moreover, the annual recurrence pattern demonstrated that the re-excision group had a higher incidence of IBTR 5 years after surgery than the other groups, while patients with involved resection margins displayed a higher incidence within the first 5 years of surgery in comparison to other groups (Figure 2).

    Figure 1
    The Kaplan-Meier curves according to initial resection margin status and age at surgery.
    Kaplan-Meier curves of IBTR for patients who achieved clear resection margins after re-excision and for those with clear resection margins at the first lumpectomy (A). After stratification according to age at operation, the survival curves of IBTR for patients younger than 50 years (B) and older than or equal to 50 years (C) are displayed. The p-values are calculated using the log-rank test and hazard ratios are calculated using the Cox regression test.

    IBTR = ipsilateral breast tumor recurrence; CI = confidence interval.

    Figure 2
    Patterns of annual recurrence incidence according to resection margin status. The annual recurrence pattern displays that the re-excision group had a higher incidence of IBTR 5 years after surgery than the other groups, while patients with involved resection margin display a high incidence within the first 5 years of surgery.
    IBTR = ipsilateral breast tumor recurrence.

    Age at the time of operation was also revealed to be significantly associated with IBTR (hazard ratio, 0.97; 95% CI, 0.95–0.99; p = 0.001), and an increased number of younger patients were included in the re-excision group compared to older patients (p < 0.001). Thus, we conducted a subgroup analysis according to the age at surgery to adjust for confounding effects between age and IBTR. The survival difference was observed for young patients (p = 0.033; hazard ratio, 1.72; 95% CI, 1.04–2.85 for age less than 50) (Figure 1B and C). Additionally, when the patients were divided according to their HR and HER2 amplification status, we observed significant differences in the HR+/HER2− and HR−/HER2− subtypes, whereas HER2-amplified tumors displayed no significant differences (Figure 3).

    Figure 3
    The Kaplan-Meier curves according to tumor subtypes.
    The Kaplan-Meier survival curves of IBTR according to HR and HER2 status of tumors are displayed: (A) HR+/HER2−; (B) HR+/HER2+; (C) HR−/HER2+; (D) HR−/HER2−. The p-values are calculated using the log-rank test and hazard ratios are calculated using the Cox regression test.

    IBTR = ipsilateral breast tumor recurrence; HR = hormone receptor; HER2 = human epidermal growth factor receptor-2; CI = confidence interval.

    Using Cox regression analysis, we adjusted for other clinicopathological variables, such as age, histologic grade, lymphovascular invasion, HR status, HER2 amplification status, Ki-67 levels, and administration of adjuvant treatments (Table 2). The results of the Cox regression analysis demonstrated that re-excision to achieve negative margins was significantly associated with the risk of IBTR after adjusting for the aforementioned variables (p = 0.030; hazard ratio, 1.69; 95% CI, 1.05–2.72). Furthermore, to further adjust for clinicopathologic features associated with IBTR, we conducted 1:1 propensity score matching yielding 1,304 patients (Supplementary Table 1). Patients who underwent re-excision still exhibited unfavorable IBTR-free survival than those who did not (p = 0.045; hazard ratio, 2.12; 95% CI, 1.00–4.47) (Supplementary Figure 2).

    Table 2
    Univariate and multivariate analyses for ipsilateral breast tumor recurrence-free survival

    IBTR patterns in patients with re-excision

    The events of IBTR can be classified as true recurrence (TR) or new primary (NP) events based on their location and histological features [16, 17]. Moreover, TR was defined as tumor recurrence in the same quadrant with the same HR/HER2 status and histological type as the original tumor. We investigated that the relapse patterns of IBTR due to technical failure to remove cancer cells were more likely to result in TR than in NP. The recurrence patterns of IBTR in both groups are displayed in Figure 4. As demonstrated in Figure 4A, the number of TR events did not differ significantly between the two groups. Additionally, the spatial patterns of IBTR, defined by the distance of recurrence from the initial tumor, did not exhibit a significant difference between patients who achieved clear margins at the initial lumpectomy and those who underwent re-excision (Figure 4B and C). Notably, regarding subtype changes between primary and recurrent tumors, 26.1% of patients displayed different tumor subtypes.

    Figure 4
    Recurrence patterns among patients with ipsilateral breast tumor recurrence.
    Recurrent tumors in 121 patients with IBTR are classified based on their location and histological features (A). Regarding the spatial pattern of IBTR, the location of recurrence relative to the original tumor (B) and the distance of recurrence from the initial tumor (C) according to the two groups are demonstrated.

    IBTR = ipsilateral breast tumor recurrence; ns = not significant.

    DISCUSSION

    A widely accepted fact is that the microscopic presence of tumor cells at the surgical margins leads to a two-fold increased risk of IBTR in patients undergoing breast conservation [18]. This association between resection margin status and the risk of recurrence has resulted in a consensus that stresses the importance of achieving a negative resection margin to minimize the risk of IBTR [1]. Accordingly, many patients with breast cancer undergo repeat surgeries to minimize the risk of recurrence [2, 3, 4]. However, the degree of benefit associated with repeated surgical excision to achieve a negative resection margin has not yet been quantitatively addressed.

    The true benefit of re-excision for clear margins can only be determined by a randomized trial comparing either performing or omitting re-excision in patients with positive resection margins; such clinical trials require substantial scientific evidence to be justified. In the present study, we used a different approach that may provide insight into this issue by comparing the outcomes between patients who achieved clear margins at initial lumpectomy and those who achieved clear margins after repeated excisions. The two-fold increased risk of IBTR with a positive resection margin could be the result of the biologically aggressive nature of the disease that led to the involvement of margins, technical failure leaving residual disease, or a combination of both. Regarding the two hypotheses, we assumed that if achieving negative margins by initial lumpectomy and repeated excision resulted in similar outcomes, then the increased IBTR risk associated with positive margins would be mainly due to technical issues, as repeated excision nullified the risk.

    In our data of 5,598 patients who underwent breast conservation, a 61% increased risk of IBTR was observed in patients with positive resection margins at the initial lumpectomy, despite all patients achieving negative resection by repeated excisions. The data indicate that a certain proportion of the two-fold increased risk of IBTR remains in patients with positive resection margins even after additional surgeries to clear the margins, as reported in a previous meta-analysis [1]. Our findings raise the possibility that the benefits associated with additional surgery to achieve negative margins may be minimal, as the inherent biology of the tumor may play a significant role in determining the risk of IBTR. For example, extensive intraductal components and lobular histology are well-known biological factors that affect resection margin status and IBTR rate [11, 12, 13, 14, 15]. The presence of multifocality and lymphovascular invasion of tumors also can induce a positive resection margin, resulting in local control failure [19, 20, 21]. Additionally, changes in the microenvironment of normal breast tissue far from the main tumor induce alterations in transforming growth factor-beta signaling and affect local recurrence [22]. Furthermore, we observed similar IBTR patterns on TR and NP regardless of re-excision, suggesting that technical failure to remove cancer cells is not likely to be the cause of the increased IBTR risk observed in patients who underwent re-excision.

    While studies have demonstrated that re-excision for breast conservation does not influence the overall survival of patients [23, 24], the oncologic benefit of re-excision for positive resection margins remains unclear. Based on a propensity score matching analysis of 2,110 patients, Sorrentino et al. [25] reported no significant benefit in local control with re-excision. However, this finding differs from that of Vos et al. [24], who reported a significantly high risk of IBTR with the omission of re-excision in patients with positive margins. However, in their study, > 50% of the patients with positive resection margins underwent mastectomy for re-excision, which made direct comparison difficult. The conflicting results regarding the benefit of re-excision for patients undergoing lumpectomy with positive resection margins, along with our present observation of a persistently increased risk of IBTR after re-excision, warrant further prospective clinical trials that can properly address this issue.

    To investigate the effect of delayed adjuvant treatment due to reoperation, we sub-grouped the re-excision group according to the timing of further resection. Among the 793 patients, 663 (83.6%) underwent further resection immediately after the excision of the main specimen, while 130 (16.4%) underwent delayed reoperation. Kaplan–Meier graphs revealed that the immediate re-excision group had an IBTR rate comparable to the delayed reoperation group (hazard ratio, 1.34; 95% CI, 0.45–4.47; p = 0.632) (Supplementary Figure 3A). In contrast, the group still displayed a worse IBTR-free survival rate than those who achieved a clear resection margin at first lumpectomy (hazard ratio, 1.67; 95% CI, 1.06–2.64; p = 0.025) (Supplementary Figure 3B). Previous studies investigated the effects of delayed adjuvant treatment on survival outcomes. Jobsen et al. [26] reported that the timing of radiotherapy in breast-conserving patients was not associated with the local recurrence rate, while Buchholz et al. [27] displayed a high local failure rate for those who started radiotherapy after 6 months or more. Another study reported that 91 or more days of delay in adjuvant chemotherapy was associated with a poor overall survival rate [28]. In the current study, the median interval between the first lumpectomy and delayed re-excision was 21 days (range, 9–51) days. Thus, an assumption can be made that the delay in adjuvant treatment did not affect the IBTR survival rate in the re-excision group.

    Cox regression analysis revealed that young age at surgery, presence of lymphovascular invasion, and positive HER2 status were also significant predictors of poor IBTR-free survival. Consistent with our results, previous studies have reported higher IBTR rates in young patients than in older patients owing to aggressive features, small resection volume, and the possibility of genetic predisposition [29, 30, 31]. The elevated IBTR rate for HER2-positive tumors can be the result of increased resistance to radiotherapy via the focal adhesion kinase-mediated pathway or resistance to endocrine therapy via the interaction effect of crosstalk between estrogen receptors and HER2 [32, 33]. Finally, tumors with lymphovascular invasion have a two-fold high risk of local recurrence [34]. Tumors presenting with lymphovascular invasion are usually accompanied by more aggressive tumor features and are associated with poor survival rates [35, 36]. In the current study, patients with lymphovascular invasion were included in the re-excision group but displayed no statistical significance between the two groups. This suggests that other biological features, such as multifocality or intraductal components, may have influenced the elevated IBTR rate in the re-excision group.

    Our study has several limitations. First, the retrospective and single-institution nature of the study requires further validation. Moreover, the lack of a pathological review by a central pathologist may have resulted in a hidden bias. However, our institution has a standardized pathology report form, and all pathologists who participated in the pathological examinations specialized in breast cancer. Second, we compared the IBTR rates of patients with positive resection margins who did not undergo additional surgery; however, only 35 patients (0.6%) did not undergo further surgery for their positive margins during the study period. Therefore, obtaining sufficient statistical evidence to determine an increased risk of IBTR in patients with positive margins was not possible. Third, a possibility may be present of inaccurate re-excision of residual tumors, which should be considered a technical issue, leaving the tumor cells in the cavity. To address this issue, we investigated the presence of tumor cells in the excised specimen. Although most patients had no pathology report for further resected specimens as we sutured them to the main specimen, 180 patients in the re-excision group were able to discern the presence of tumor cells, and 44 (24.4%) patients had no residual tumor cells, which was comparable to that reported in other studies [37, 38]. Only 1 of 44 patients demonstrated IBTR while 5 patients recurred among those with residual tumor cells in the cavity (χ2 p-value = 0.652). Additionally, the IBTR-free survival rate was not significantly different between the two groups (p = 0.839, hazard ratio, 0.80, 95% CI, 0.09–6.89, data not displayed). Interestingly, among patients with no residual tumor, nine did not undergo cavity shaving, and none of them exhibited IBTR events. Moreover, to further investigate the possible effects of technical failure, we reviewed 115 patients who underwent total mastectomy to achieve a clear resection margin during the same period as the current study. Compared to patients who underwent breast-conserving surgery for re-excision, no significant difference was observed in the number of patients without residual tumor cells or the IBTR-free survival rate (Supplementary Figure 4). These findings further confirm that the impact of technical failure on IBTR was sufficiently negated. Finally, we could not elucidate differences in the pathological characteristics of the tumors between the groups. The presence of extensive intraductal components, the presence of microscopic multifocal tumors, or the nature of the spatial tumor growth can all be the pathologic phenotypes identified in the patients with initial positive margins. However, we could not perform a detailed review of the tumor pathology specimens.

    In conclusion, our data demonstrated that patients with positive resection margins after breast conservation have an increased risk of IBTR, which cannot be completely nullified by achieving negative resection margins through re-excision. Patients who underwent re-excision for initial positive margins had an increased risk of IBTR, even after achieving a final negative margin, compared to patients with initially negative margins. This increased risk of IBTR is mostly observed in young patients and delayed cases.

    SUPPLEMENTARY MATERIALS

    Supplementary Table 1

    Clinicopathologic characteristics of patients after 1:1 propensity score matching

    Click here to view.(31K, xls)

    Supplementary Figure 1

    The Kaplan-Meier curves according to final resection margin status.

    Click here to view.(543K, ppt)

    Supplementary Figure 2

    The Kaplan-Meier curves according to initial resection margin status after 1:1 propensity score matching.

    Click here to view.(602K, ppt)

    Supplementary Figure 3

    The Kaplan-Meier curves according to the timing of further resection.

    Click here to view.(919K, ppt)

    Supplementary Figure 4

    Comparison of the operation method for re-excision.

    Click here to view.(843K, ppt)

    Notes

    Funding:This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HA15C0011). This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. NRF-2019R1A2C2005277).

    Conflict of Interest:Han-Byoel Lee and Wonshik Han is currently a board member and holds stocks of DCGen, Co., Ltd. Other authors declare no relevant conflict of interest to this study.

    Data Availability:The datasets used in this study are available from the corresponding author upon request.

    Author Contributions:

    • Conceptualization: Moon HG.

    • Data curation: Cheun JH.

    • Formal analysis: Cheun JH.

    • Funding acquisition: Moon HG.

    • Investigation: Cheun JH, Moon HG.

    • Supervision: Moon HG.

    • Writing - original draft: Cheun JH, Moon HG.

    • Writing - review & editing: Cheun JH, Kim HK, Lee HB, Han W, Moon HG.

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    MeSH Terms
    Biological Products
    Breast
    Breast Neoplasms
    Follow-Up Studies
    Humans
    Margins of Excision
    Mastectomy, Segmental*
    Neoplasm Recurrence, Local
    Recurrence*
    Retrospective Studies
    Metrics
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