Comparison of locoregional recurrence risk among nipple-sparing mastectomy, skin-sparing mastectomy, and simple mastectomy in patients with ductal carcinoma in situ: A single-center study

Comparison of locoregional recurrence risk among nipple-sparing mastectomy, skin-sparing mastectomy, and simple mastectomy in patients with ductal carcinoma in situ: A single-center study | 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 Comparison of locoregional recurrence risk among nipple-sparing mastectomy, skin-sparing mastectomy, and simple mastectomy in patients with ductal carcinoma in situ: A single-center study Mika Nashimoto, Yuko Asano, Hiroki Matsui, Youichi Machida, Eisuke Fukuma This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3901814/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Jul, 2024 Read the published version in Breast Cancer → Version 1 posted 4 You are reading this latest preprint version Abstract Background In invasive breast cancer, there is no difference in mid- and long-term oncological safety results between nipple-sparing mastectomy (NSM), skin-sparing mastectomy (SSM) and simple mastectomy (SM). However, there are few reports on ductal carcinoma in situ (DCIS). This study aimed to compare the local recurrence and survival rates of the three techniques (NSM, SSM, and SM) in Japanese patients undergoing mastectomy for DCIS. Methods Patients undergoing NSM, SSM, and SM at our institution between 2006 and 2015 were identified, and their outcomes were analyzed. Results The mean follow-up period was 80.4 months (standard deviation [SD]: 37.1 months). NSM was performed in 152 cases, SSM in 49, and SM in 44. Five of 245 patients developed local recurrences. Four of these patients had invasive cancer. The primary endpoints of 5-year cumulative local recurrence were 2.4% (95% confidence interval [CI]: 0.0–5.0) for NSM, 2.2% (95% CI: 0.0–6.3) for SSM, and 0% (95% CI: 0.0–0.0) for SM. There were no significant differences in the 5-year local recurrence rate. Conclusions In conclusion, in our single-center, retrospective study, SSM and NSM showed oncological safety for DCIS that was comparable to that of conventional simple mastectomy. nipple-sparing mastectomy (NSM) skin-sparing mastectomy (SSM) simple mastectomy (SM) ductal carcinoma in situ (DCIS) local recurrence Figures Figure 1 Figure 2 Introduction Ductal carcinoma in situ (DCIS) is typically asymptomatic and is detected during breast screening [ 1 ]. The proportion of women diagnosed with DCIS has increased to approximately 14–15% of those diagnosed with breast cancer in Japan [ 2 – 5 ]. The incidence of DCIS is on the rise, primarily attributed to the widespread implementation of mammographic screening. The increased utilization of mammography as a screening tool has led to the detection of a higher number of DCIS cases, as it allows for the identification of non-invasive breast abnormalities at an early stage [ 6 ]. At present, surgical resection is the primary approach for treating DCIS. When dealing with multicentric or extensive DCIS, mastectomy is the accepted standard of treatment [ 7 ]. In recent years, various surgical techniques have been developed for procedures such as NSM (nipple-sparing mastectomy) and SSM (skin-sparing mastectomy). These are new surgical approaches that enable cosmetic appearance to be retained with oncological safety [ 8 – 10 ]. A meta-analysis of patients with invasive breast cancer indicated that overall survival, disease-free survival, and local recurrence rates in patients who underwent SSM/NSM did not differ from those of patients who underwent a conventional simple mastectomy [ 11 ]. In our previous study, the local recurrence rate was 2.6% after endoscopy-assisted NSM in patients with breast cancer [ 12 ]. However, few studies have restricted their focus to DCIS cases and have demonstrated that SSM/NSM is a non-inferior technique in terms of oncological safety compared to conventional mastectomy. We performed a retrospective analysis of patients who underwent mastectomy for DCIS and compared the postoperative local recurrence rates among these techniques. This study aimed to evaluate the oncological safety and efficacy of NSM/SSM as surgical treatment options for DCIS. Methods Study population and data collection This was a single-center, retrospective cohort study. We reviewed the records of patients with DCIS who underwent mastectomy between January 2006 and December 2015 at our institution. No cases underwent risk reducing mastectomy. The following patients were excluded from further analysis: 1) patients whose contralateral breast was treated for invasive cancer in the previous or synchronous period; 2) patients without immunohistochemistry reports. All data on patient characteristics, surgical details, and postoperative courses were obtained from the medical records. Pathological information, including nuclear grade, [ 13 ] necrosis, and receptor status, was obtained from the pathology reports. We did not routinely test for Her2 expression in DCIS, so it was not included in the data collected in this study. The follow-up period was defined as the time from surgery to the last visit. The follow-up period was terminated on July 8, 2021. This study included only female patients with DCIS. Our institution follows the guideline that does not recommend adjuvant therapy, such as radiation therapy and endocrine therapy, for DCIS after mastectomy [ 14 ]. Ethics This study was conducted in compliance with the domestic laws of Japan, ethical guidelines for medical research in Japan, and the Declaration of Helsinki. As a retrospective observational study, patient consent was obtained through an opt-out approach. This study was approved by the institutional review board of Kameda Medical Center (No. 20–120). Presurgical planning All patients underwent mammography, breast ultrasound, and 1.5 or 3-Tesla breast MRI to assess the tumor size and location, as well as investigate the presence of any other tumors in the breast. All patients were diagnosed with DCIS by ultrasound-guided needle biopsy, vacuum-assisted biopsy, or excisional biopsy. Indications for mastectomy included cases where breast-conserving surgery was contraindicated due to a large tumor, multifocal or multicentric tumors, the possibility of poor cosmetic outcomes due to the tumor-size-to-breast-volume ratio, or patient preference. Clinical features and imaging findings without skin or muscle involvement were considered indications for SSM and NSM. Of these, we offer the option of NSM for patients with no clinical nipple discharge, no Paget disease, and no infiltration of the nipple-areola complex on MRI. Cases with uncertain infiltration of the nipple-areola complex on MRI are individually evaluated during our hospital's preoperative conference. Surgical procedure In every case, a sentinel lymph node (SLN) biopsy was performed prior to mastectomy using blue dye injection and radioisotopes guided by a gamma probe. The incisions used for each technique are illustrated in Fig. 1 . Mastectomy flaps were created in the subdermal plane using either electrocautery or scissors. We used endoscopic assistance for the dissection of the prefectorial major muscle in cases of NSM and SSM. To ensure oncological safety and examine whether cancer had extended to the nipple margins, an intraoperative subareolar tissue biopsy was performed in all cases of NSM [ 12 ]. in the event of a positive biopsy result, NSM was switched to SSM. Follow-up evaluation Patients were routinely followed up every 3–6 months for the first 5 years after surgery and every year thereafter. Abnormal findings on physical examination and ultrasonography were further evaluated using MRI and biopsy. Locoregional recurrence was defined as biopsy-diagnosed cancer of the skin, subcutaneous tissue, chest wall, or regional lymph nodes of the ipsilateral breast. Statistical analysis The primary outcome was the 5-year locoregional recurrence rate as the first event after mastectomy. The 5-year locoregional recurrence rate was defined as the period from the date of surgery to the last follow-up without local recurrence. Comparisons of observed items between surgical procedures were performed using a one-way analysis of variance for continuous variables and Fisher’s exact test for categorical variables. For the time to recurrence from surgery (recurrence-free survival) for each surgical technique (NSM, SSM, and simple mastectomy [SM]), survival time analysis was performed using the Kaplan–Meier method. A log-rank test was performed for comparisons between groups. The Cox proportional hazards model was used to determine whether surgical techniques affected recurrence-free survival after adjusting for age and body mass index (BMI). Results Between January 1, 2006, and December 31, 2015, a total of 311 patients underwent a mastectomy for DCIS. Among these patients, 66 were excluded from the study for the following reasons: 1) patients whose contralateral breast was treated for invasive cancer in the previous or synchronous period (39 cases); and 2) patients without immunohistochemistry reports (27 cases). The remaining 245 cases were evaluated, with NSM (N = 152), SSM (N = 49), and SM (N = 44) procedures performed (Fig. 1 ). The patient demographics and pathological characteristics of the NSM, SSM, and SM groups are shown in Table 1 . The groups differed significantly in age (p < 0.001), BMI (p < 0.001), and reconstructive surgery (p < 0.001). The patients in the NSM group were younger (average age, 49.07 years). They also had a lower BMI (average 21.39) and were more likely to undergo immediate reconstructive surgery (35.5%). Statistically non-significant differences were observed among the three groups in terms of nuclear grade, preference for necrosis, and hormone receptor status. No, cases with positive surgical margins required reoperation or radiotherapy. Table 1 Patient demographics and pathologic characteristics in the NSM, SSM, and SM groups NSM (n = 152) SSM (n = 49) SM (n = 44) p value Number of patients 152 49 44 Age (years, mean [SD]) 49.07 (9.20) 50.58 (10.31) 65.59 (9.81) < 0.001 BMI (kg/m 2 , mean [SD]) 21.39 (3.01) 21.02 (3.27) 23.75 (4.36) < 0.001 Side 0.055 Left (%) 73 (48.0) 23 (46.9) 15 (34.1) Right (%) 58 (38.2) 18 (36.7) 27 (61.4) Bilateral (%) 21 (13.8) 8 (16.3) 2 (4.5) Reconstruction type < 0.001 TE (%) 54 (35.5) 12 (24.5) 0 (0.0) SBI (%) AUTO (%) 0 (0.0) 0 (0.0) 0 (0.0) Other (%) 0 (0.0) 0 (0.0) 0 (0.0) None (%) 98 (64.1) 37 (75.5) 44 (100) Lymph-node operation (%) 0.426 Ax 3 (2.0) 1 (2.0) 0 (0.0) SN 146 (96.1) 47 (95.9) 41 (93.2) No surgery 3 (2.0) 1 (2.0) 3 (6.8) Nuclear grade 0.846 1 27 (18.4) 10 (20.4) 10 (23.3) 2 76 (51.7) 23 (46.9) 23 (53.5) 3 44 (29.9) 16 (32.7) 10 (23.3) Presence of necrosis (%) 79 (52.7) 33 (67.3) 23 (52.3) 0.177 ER Positive (%) 140 (93.3) 40 (81.6) 39 (88.6) 0.055 Negative (%) 12 (7.9) 9 (18.4) 5 (11.4) PR Positive (%) 135 (90.0) 38 (77.6) 34 (77.3) 0.027 Negative (%) 17 (11.7) 11 (25.0) 10 (22.7) Follow-up period (months, (mean [SD]) 78.42 (40.35) 85.81 (32.23) 81.39 (29.75) 0.472 SD: standard deviation, BMI: body mass index, NSM: nipple sparing mastectomy, SSM: skin sparing mastectomy, SM: simple mastectomy, ER: estrogen hormone receptor expression, PR: progesterone hormone receptor expression, TE: tissue expander, SBI: silicon breast implant, AUTO: autologous breast reconstruction, Other: mesh, Ax: axillary dissection, SN: sentinel lymph node biopsy The median follow-up period was 80.4 months (standard deviation [SD]: 37.1 months). The median follow-up period was 78.42 months (SD: 40.35) in the NSM group, 85.81 months (SD: 29.75) in the SSM group, and 85.81 months (SD: 32.23) in the SM group. Five of the 248 patients had locoregional recurrence, four had undergone NSM, and one had undergone SSM (Table 2 ). There were four cases of recurrence in the subcutaneous tissue, or nipple, and one case of recurrence in the axillary lymph node. No distant metastases were observed in any of the five cases. Two patients died during follow-up for reasons unrelated to breast cancer. Table 2 Outcomes of nipple sparing mastectomy, skin sparing mastectomy, and simple mastectomy cohorts NSM SSM SM p value Number 152 49 44 No recurrence (%) 147 (96.7) 48 (98.0) 43 (97.7) 0.599 Locoregional recurrence a (%) 4 (2.6) 1 (2.0) 0 (0.0) Distant metastasis (%) 0 (0.0) 0 (0.0) 0 (0.0) Death b (%) 1 (0.7) 0 (0.0) 1 (2.3) NSM: nipple sparing mastectomy, SSM: skin sparing mastectomy, SM: simple mastectomy a Locoregional recurrence: a recurrence in either the skin, nipple areola complex, chest wall, or regional nodes b Death: any cause of death The primary endpoint of 5-year cumulative local recurrence was 2.4% (95% confidence interval [CI]: 0.0–5.0) for NSM, 2.2% (95% CI: 0.0–6.3) for SSM, and 0.0% for SM (Table 3 ). There were no significant differences in the 5-year local recurrence rate, which was the primary outcome. Table 3 Five-year cumulative local recurrence as measured by the Kaplan-Meier method NSM (n = 152) SSM (n = 49) SM (n = 44) Estimated 5 years cumulative local recurrence a 0.024 (0-0.05) 0.022 (0-0.063) - NSM: nipple-sparing mastectomy, SSM: skin-sparing mastectomy, SM: simple mastectomy a A recurrence in either the ipsilateral breast/chest wall or regional nodes All values are shown as cumulative local recurrence and 95% confidential intervals. Table 4 summarizes the five patients with locoregional recurrence. The median time from surgery to locoregional recurrence was 26.79 months (interquartile range: 18.94–46.65). Of the five cases with locoregional recurrence, four patients had received NSM, one of whom had recurrence at the nipple-areola complex. Locoregional recurrence was detected by physical examination in three patients and by ultrasound in two patients. Primary breast cancer characteristics were hormone receptor positivity and nuclear grade 1–2. Surgical pathology showed that four of the five patients had negative margins, and the pathology of the recurrent tumor was DCIS in one case and IDC in the others. All the patients underwent excision for cancer recurrence. Subsequently, one patient developed a second local recurrence, one was lost to follow-up due to transfer to a different hospital, and three patients were alive with no recurrence. Table 4 Patient characteristics and outcomes of cases with cancer recurrence Patient No. 1 2 3 4 5 Age at time of surgery (Years) 40 56 35 47 44 Surgical procedure NSM NSM NSM NSM SSM Character of primary tumor Size a (mm) 40 67 55 54 32 Surgical margin Negative Negative 0.3mm Negative Negative ER/PR status +/+ +/+ +/+ +/+ +/+ Nuclear grade 1 2 2 1 2 TND b (mm) 15 0 8 5 0 Time to recurrence (Months) 26 46 72 11 18 Detection of tumor recurrence lump US US lump lump Location of tumor recurrence sub-cutaneous areola lymph node sub-cutaneous sub-cutaneous Pathology of recurring tumor DCIS IDC IDC IDC IDC Treatment for tumor recurrence Surgery + + + + + Radiation - + + + - Endocrine therapy - + - + + Chemotherapy - - + - - Follow-up after recurrence Second recurrence Alive Transfer to hospital Alive Alive NSM: nipple-sparing mastectomy, SSM: skin-sparing mastectomy, US: ultrasonography, DCIS: ductal carcinoma in situ, IDC: invasive ductal carcinoma, TND: tumor-nipple distance a Size: Lesion extent was measured by MRI. b TND: The minimum TND measured by MRI The Cox proportional hazards model showed no significant difference in the risk of local recurrence according to treatment choice, even after adjusting for age and BMI (hazard ratio [HR] for SM: 0 [0-inf], HR for SSM: 0.66 [0.07–6.1]). Discussion This retrospective cohort study of 245 patients who underwent mastectomy for DCIS examined the risk of local recurrence for three techniques: SM, SSM, and NSM. Four of the five patients who had recurrence underwent NSM, whereas the 5-year postoperative cumulative rates, compared using the log-rank test, showed no significant differences among the three groups. The pathology of the recurrent tumor was invasive recurrence in four of the five patients. There have been some reports on the long-term outcomes of NSM and SSM in patients with breast cancer, including DCIS [ 15 – 17 ]. The long-term outcomes of NSM and SSM have been shown to be as oncologically as safe as simple mastectomy. In previous studies focusing on the 10-year outcomes of DCIS, the 10-year local recurrence rate was 2.6% [ 18 ]. Previous studies on local recurrence rates of NSM and SSM for DCIS have reported rates of 4.5% [ 19 ] and 0.97% [ 20 ] at 10 years of follow-up. The results of our study were comparable to those of previous studies. Predictors of local recurrence in DCIS are tumor size, young age, high nuclear grade, negative hormone receptor and human epidermal growth factor receptor 2-positive, tumor necrosis, and surgical margins [ 19 , 21 – 24 ]. However, even after adjusting for age and BMI, the recurrence rate did not change in each group due to the small number of events, and it was not possible to examine the risk factors for recurrence in our study. Regarding surgical indications, The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction [ 14 ] states that the absence of breast cancer extension into the nipple or skin is the criterion for NSM or SSM. However, the methods for evaluating the absence of breast cancer extension into the nipple or skin vary between institutions. Previous studies have demonstrated that skin sparing is feasible from an oncological safety perspective when the distance between the tumor and dermis is > 2 mm on breast ultrasound. [ 25 ] We do not have a specific criterion of 2 mm for the distance between the tumor and the skin in skin-sparing mastectomy. Regarding the criteria for nipple-areola complex preservation, the indication for preserving the nipple-areola complex is defined as cases without abnormal nipple enhancement connected to the lesion on MRI. In a previous retrospective study from our institution, 11 of 404 patients who underwent NSM for breast cancer had local recurrence (median follow-up of 61 months); two patients had recurrence at the conserved nipple-areola complex [ 12 ]. Previous single-center cohort studies reported the NSM criterion as 2 cm from the nipple-areola complex based on preoperative imaging [ 26 , 27 ]. The new National Comprehensive Cancer Network (NCCN) guidelines [ 28 ] presented NSM criteria of 1 cm from the nipple-areola complex, and other recent matched cohort studies have shown that, even when the tumor-nipple distance (TND) is less than 1 cm on imaging, oncological safety is not different from the group with a TND greater than 1 cm [ 29 ]. In our institution, patients are candidates for NSM if they have no clinical findings, that is, no bloody nipple discharge, no Paget disease, and no infiltration within the nipple on MRI. A negative result on a routine intraoperative subareolar biopsy was an indication for NSM, and TND was not considered. It seems that the eligibility criteria for NSM and SSM at our hospital are acceptable. Breast MRI is a recommended method for diagnosing the spread of breast cancer, as studies indicate its effectiveness in detecting DCIS, surpassing the sensitivity of mammography [ 30 – 32 ]. Moreover, it is particularly valuable in assessing nipple involvement to identify potential candidates for nipple-sparing mastectomy (NSM) [ 33 ]. The utilization of breast MRI not only improves the detection of breast cancer spread and DCIS compared to mammography, but also serves as a crucial tool for evaluating nipple involvement and determining eligibility for NSM. The integration of MRI into surgical decision-making processes holds the potential to expand eligibility for both NSM and SSM. Our study had several limitations. We only assessed whether the type of mastectomy was a risk factor for DCIS recurrence. The relationship between DCIS subtypes based on molecular biomarkers (e.g., ER, PR, and HER2 status) and the risk of recurrence could not be analyzed. A short follow-up period of 5 years may also have underestimated the occurrence of recurrence. In our series, four of the five cases of recurrence involved invasive cancers. Patients who experience recurrence after mastectomy for DCIS are more likely to have an advanced recurrence than those who experience recurrence after breast conservation surgery, suggesting they may have a higher-risk profile [ 34 ]. We will continue to follow patients and analyze the association between local control and the risk of recurrence for long-term results. Further studies are also needed to follow up after treatment for recurrent tumors and compare prognoses, including distant metastasis-free survival and overall survival. In conclusion, in our single-center, retrospective study, SSM and NSM showed oncological safety for DCIS that was comparable to that of conventional mastectomy. Preoperative breast ultrasound and MRI, in addition to mammography, are useful in determining the surgical approach. Declarations Conflict of Interest The authors declare no conflicts of interest associated with this research. 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Breast Cancer Res Treat. 2021;186:617–24. https://doi.org/10.1007/s10549-021-06129-3 Cite Share Download PDF Status: Published Journal Publication published 17 Jul, 2024 Read the published version in Breast Cancer → Version 1 posted Reviewers agreed at journal 04 Feb, 2024 Reviewers invited by journal 04 Feb, 2024 Editor assigned by journal 31 Jan, 2024 First submitted to journal 30 Jan, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3901814","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":271022826,"identity":"4ee0262d-8cd6-4f5e-a1c4-bdb7aa6403be","order_by":0,"name":"Mika Nashimoto","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIiWNgGAWjYDACZjYG5j88YNYBICEhQ5QWBh6gOh4GtgSQFh4irAFpsQFp4TEAcQlr0W1nS/wgkbNNzp695/OrGzUWPAzsh49uwKfF7DDbYQmDM7eNeXjObrPOOQZ0GE9a2g38WtgbJBJ7bif2SORuM85hA2qR4DEjpKX5x8F/IC05z4xz/hGlhe2YZAMPWAvz49w24rSkWTPwAP1y5pgZc26fBA8bQb+cP2Z8G6hFjr29+fHnnG91cvzsh4/h1YIM2CTAJLHKQYD5AymqR8EoGAWjYOQAAKdKQ5xmRyX3AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0009-0005-1398-8817","institution":"Kameda Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Mika","middleName":"","lastName":"Nashimoto","suffix":""},{"id":271022827,"identity":"78d968de-6faf-4c06-a26a-7e3526fe6526","order_by":1,"name":"Yuko Asano","email":"","orcid":"","institution":"Kameda Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Yuko","middleName":"","lastName":"Asano","suffix":""},{"id":271022828,"identity":"f45c2157-af35-4057-987a-4cdfe19b12bf","order_by":2,"name":"Hiroki Matsui","email":"","orcid":"","institution":"Kameda Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Hiroki","middleName":"","lastName":"Matsui","suffix":""},{"id":271022829,"identity":"30e7d8ca-cd40-4159-ba3e-04a89c5bc9d7","order_by":3,"name":"Youichi Machida","email":"","orcid":"","institution":"Kameda Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Youichi","middleName":"","lastName":"Machida","suffix":""},{"id":271022830,"identity":"77ca667c-ea13-4ee8-8775-02e8a89358a8","order_by":4,"name":"Eisuke Fukuma","email":"","orcid":"","institution":"Kameda Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Eisuke","middleName":"","lastName":"Fukuma","suffix":""}],"badges":[],"createdAt":"2024-01-27 04:17:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3901814/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3901814/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s12282-024-01613-2","type":"published","date":"2024-07-17T16:05:01+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":50752574,"identity":"9124110e-834e-4ae6-9776-bc027fc70cfc","added_by":"auto","created_at":"2024-02-06 17:49:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":138678,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eType of skin incision\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA skin incision was designed as shown.\u003c/p\u003e","description":"","filename":"Fig12.png","url":"https://assets-eu.researchsquare.com/files/rs-3901814/v1/db5434b72b265d024b3b1b47.png"},{"id":50752573,"identity":"0a6ff8c5-1df1-4332-8c81-d29c7bffb1aa","added_by":"auto","created_at":"2024-02-06 17:49:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":27808,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatient selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis figure represents the included and excluded cases in the collected data.\u003c/p\u003e\n\u003cp\u003eDCIS: ductal carcinoma in situ, NSM: nipple-sparing mastectomy, SSM: skin-sparing mastectomy, SM: simple mastectomy.\u003c/p\u003e","description":"","filename":"Fi22.png","url":"https://assets-eu.researchsquare.com/files/rs-3901814/v1/65b289399fae8ef433839a2f.png"},{"id":61594683,"identity":"78923e68-17c4-4637-8b1b-f652571114cd","added_by":"auto","created_at":"2024-08-01 17:15:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":691994,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3901814/v1/218d1a20-f03f-4353-b331-b9b3c59e84ff.pdf"}],"financialInterests":"","formattedTitle":"Comparison of locoregional recurrence risk among nipple-sparing mastectomy, skin-sparing mastectomy, and simple mastectomy in patients with ductal carcinoma in situ: A single-center study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDuctal carcinoma in situ (DCIS) is typically asymptomatic and is detected during breast screening [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The proportion of women diagnosed with DCIS has increased to approximately 14\u0026ndash;15% of those diagnosed with breast cancer in Japan [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The incidence of DCIS is on the rise, primarily attributed to the widespread implementation of mammographic screening. The increased utilization of mammography as a screening tool has led to the detection of a higher number of DCIS cases, as it allows for the identification of non-invasive breast abnormalities at an early stage [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAt present, surgical resection is the primary approach for treating DCIS. When dealing with multicentric or extensive DCIS, mastectomy is the accepted standard of treatment [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In recent years, various surgical techniques have been developed for procedures such as NSM (nipple-sparing mastectomy) and SSM (skin-sparing mastectomy). These are new surgical approaches that enable cosmetic appearance to be retained with oncological safety [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. A meta-analysis of patients with invasive breast cancer indicated that overall survival, disease-free survival, and local recurrence rates in patients who underwent SSM/NSM did not differ from those of patients who underwent a conventional simple mastectomy [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In our previous study, the local recurrence rate was 2.6% after endoscopy-assisted NSM in patients with breast cancer [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, few studies have restricted their focus to DCIS cases and have demonstrated that SSM/NSM is a non-inferior technique in terms of oncological safety compared to conventional mastectomy. We performed a retrospective analysis of patients who underwent mastectomy for DCIS and compared the postoperative local recurrence rates among these techniques. This study aimed to evaluate the oncological safety and efficacy of NSM/SSM as surgical treatment options for DCIS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population and data collection\u003c/h2\u003e \u003cp\u003eThis was a single-center, retrospective cohort study. We reviewed the records of patients with DCIS who underwent mastectomy between January 2006 and December 2015 at our institution. No cases underwent risk reducing mastectomy. The following patients were excluded from further analysis: 1) patients whose contralateral breast was treated for invasive cancer in the previous or synchronous period; 2) patients without immunohistochemistry reports.\u003c/p\u003e \u003cp\u003eAll data on patient characteristics, surgical details, and postoperative courses were obtained from the medical records. Pathological information, including nuclear grade, [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] necrosis, and receptor status, was obtained from the pathology reports. We did not routinely test for Her2 expression in DCIS, so it was not included in the data collected in this study. The follow-up period was defined as the time from surgery to the last visit. The follow-up period was terminated on July 8, 2021. This study included only female patients with DCIS. Our institution follows the guideline that does not recommend adjuvant therapy, such as radiation therapy and endocrine therapy, for DCIS after mastectomy [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eEthics\u003c/h2\u003e \u003cp\u003e This study was conducted in compliance with the domestic laws of Japan, ethical guidelines for medical research in Japan, and the Declaration of Helsinki. As a retrospective observational study, patient consent was obtained through an opt-out approach. This study was approved by the institutional review board of Kameda Medical Center (No. 20\u0026ndash;120).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003ePresurgical planning\u003c/h2\u003e \u003cp\u003eAll patients underwent mammography, breast ultrasound, and 1.5 or 3-Tesla breast MRI to assess the tumor size and location, as well as investigate the presence of any other tumors in the breast. All patients were diagnosed with DCIS by ultrasound-guided needle biopsy, vacuum-assisted biopsy, or excisional biopsy. Indications for mastectomy included cases where breast-conserving surgery was contraindicated due to a large tumor, multifocal or multicentric tumors, the possibility of poor cosmetic outcomes due to the tumor-size-to-breast-volume ratio, or patient preference. Clinical features and imaging findings without skin or muscle involvement were considered indications for SSM and NSM. Of these, we offer the option of NSM for patients with no clinical nipple discharge, no Paget disease, and no infiltration of the nipple-areola complex on MRI. Cases with uncertain infiltration of the nipple-areola complex on MRI are individually evaluated during our hospital's preoperative conference.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eSurgical procedure\u003c/h2\u003e \u003cp\u003eIn every case, a sentinel lymph node (SLN) biopsy was performed prior to mastectomy using blue dye injection and radioisotopes guided by a gamma probe. The incisions used for each technique are illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Mastectomy flaps were created in the subdermal plane using either electrocautery or scissors. We used endoscopic assistance for the dissection of the prefectorial major muscle in cases of NSM and SSM. To ensure oncological safety and examine whether cancer had extended to the nipple margins, an intraoperative subareolar tissue biopsy was performed in all cases of NSM [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. in the event of a positive biopsy result, NSM was switched to SSM.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eFollow-up evaluation\u003c/h2\u003e \u003cp\u003ePatients were routinely followed up every 3\u0026ndash;6 months for the first 5 years after surgery and every year thereafter. Abnormal findings on physical examination and ultrasonography were further evaluated using MRI and biopsy. Locoregional recurrence was defined as biopsy-diagnosed cancer of the skin, subcutaneous tissue, chest wall, or regional lymph nodes of the ipsilateral breast.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe primary outcome was the 5-year locoregional recurrence rate as the first event after mastectomy. The 5-year locoregional recurrence rate was defined as the period from the date of surgery to the last follow-up without local recurrence.\u003c/p\u003e \u003cp\u003eComparisons of observed items between surgical procedures were performed using a one-way analysis of variance for continuous variables and Fisher\u0026rsquo;s exact test for categorical variables. For the time to recurrence from surgery (recurrence-free survival) for each surgical technique (NSM, SSM, and simple mastectomy [SM]), survival time analysis was performed using the Kaplan\u0026ndash;Meier method. A log-rank test was performed for comparisons between groups. The Cox proportional hazards model was used to determine whether surgical techniques affected recurrence-free survival after adjusting for age and body mass index (BMI).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eBetween January 1, 2006, and December 31, 2015, a total of 311 patients underwent a mastectomy for DCIS. Among these patients, 66 were excluded from the study for the following reasons: 1) patients whose contralateral breast was treated for invasive cancer in the previous or synchronous period (39 cases); and 2) patients without immunohistochemistry reports (27 cases). The remaining 245 cases were evaluated, with NSM (N\u0026thinsp;=\u0026thinsp;152), SSM (N\u0026thinsp;=\u0026thinsp;49), and SM (N\u0026thinsp;=\u0026thinsp;44) procedures performed (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The patient demographics and pathological characteristics of the NSM, SSM, and SM groups are shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The groups differed significantly in age (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), BMI (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and reconstructive surgery (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The patients in the NSM group were younger (average age, 49.07 years). They also had a lower BMI (average 21.39) and were more likely to undergo immediate reconstructive surgery (35.5%). Statistically non-significant differences were observed among the three groups in terms of nuclear grade, preference for necrosis, and hormone receptor status. No, cases with positive surgical margins required reoperation or radiotherapy.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ePatient demographics and pathologic characteristics in the NSM, SSM, and SM groups\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNSM (n\u0026thinsp;=\u0026thinsp;152)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSSM (n\u0026thinsp;=\u0026thinsp;49)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSM (n\u0026thinsp;=\u0026thinsp;44)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNumber of patients\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e152\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e44\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge (years, mean [SD])\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49.07 (9.20)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50.58 (10.31)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e65.59 (9.81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e, mean [SD])\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.39 (3.01)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.02 (3.27)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.75 (4.36)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSide\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.055\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLeft (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e73 (48.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23 (46.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15 (34.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRight (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e58 (38.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18 (36.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27 (61.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBilateral (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21 (13.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (16.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eReconstruction type\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTE (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e54 (35.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12 (24.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSBI (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAUTO (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOther (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNone (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e98 (64.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37 (75.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e44 (100)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLymph-node operation (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.426\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAx\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSN\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e146 (96.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e47 (95.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41 (93.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo surgery\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (6.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNuclear grade\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.846\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27 (18.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (20.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (23.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e76 (51.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23 (46.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23 (53.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e44 (29.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16 (32.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (23.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePresence of necrosis (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e79 (52.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33 (67.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23 (52.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.177\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eER\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePositive (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e140 (93.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40 (81.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39 (88.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.055\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12 (7.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (18.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (11.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePositive (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e135 (90.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38 (77.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34 (77.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.027\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17 (11.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (25.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (22.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFollow-up period (months, (mean [SD])\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e78.42 (40.35)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e85.81 (32.23)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e81.39 (29.75)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.472\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003eSD: standard deviation, BMI: body mass index, NSM: nipple sparing mastectomy, SSM: skin sparing mastectomy, SM: simple mastectomy, ER: estrogen hormone receptor expression, PR: progesterone hormone receptor expression, TE: tissue expander, SBI: silicon breast implant, AUTO: autologous breast reconstruction, Other: mesh, Ax: axillary dissection, SN: sentinel lymph node biopsy\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe median follow-up period was 80.4 months (standard deviation [SD]: 37.1 months). The median follow-up period was 78.42 months (SD: 40.35) in the NSM group, 85.81 months (SD: 29.75) in the SSM group, and 85.81 months (SD: 32.23) in the SM group. Five of the 248 patients had locoregional recurrence, four had undergone NSM, and one had undergone SSM (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). There were four cases of recurrence in the subcutaneous tissue, or nipple, and one case of recurrence in the axillary lymph node. No distant metastases were observed in any of the five cases. Two patients died during follow-up for reasons unrelated to breast cancer.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eOutcomes of nipple sparing mastectomy, skin sparing mastectomy, and simple mastectomy cohorts\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNSM\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSSM\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSM\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNumber\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e152\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e44\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo recurrence (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e147 (96.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e48 (98.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43 (97.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.599\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLocoregional recurrence\u003csup\u003ea\u003c/sup\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (2.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDistant metastasis (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDeath\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (0.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (2.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003eNSM: nipple sparing mastectomy, SSM: skin sparing mastectomy, SM: simple mastectomy\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003eLocoregional recurrence: a recurrence in either the skin, nipple areola complex, chest wall, or regional nodes\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003e\u003csup\u003eb\u003c/sup\u003eDeath: any cause of death\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe primary endpoint of 5-year cumulative local recurrence was 2.4% (95% confidence interval [CI]: 0.0\u0026ndash;5.0) for NSM, 2.2% (95% CI: 0.0\u0026ndash;6.3) for SSM, and 0.0% for SM (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). There were no significant differences in the 5-year local recurrence rate, which was the primary outcome.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eFive-year cumulative local recurrence as measured by the Kaplan-Meier method\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNSM (n\u0026thinsp;=\u0026thinsp;152)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSSM (n\u0026thinsp;=\u0026thinsp;49)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSM (n\u0026thinsp;=\u0026thinsp;44)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEstimated 5 years cumulative local recurrence\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.024 (0-0.05)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.022 (0-0.063)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\"\u003eNSM: nipple-sparing mastectomy, SSM: skin-sparing mastectomy, SM: simple mastectomy\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003eA recurrence in either the ipsilateral breast/chest wall or regional nodes\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\"\u003eAll values are shown as cumulative local recurrence and 95% confidential intervals.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e summarizes the five patients with locoregional recurrence. The median time from surgery to locoregional recurrence was 26.79 months (interquartile range: 18.94\u0026ndash;46.65). Of the five cases with locoregional recurrence, four patients had received NSM, one of whom had recurrence at the nipple-areola complex. Locoregional recurrence was detected by physical examination in three patients and by ultrasound in two patients. Primary breast cancer characteristics were hormone receptor positivity and nuclear grade 1\u0026ndash;2. Surgical pathology showed that four of the five patients had negative margins, and the pathology of the recurrent tumor was DCIS in one case and IDC in the others. All the patients underwent excision for cancer recurrence. Subsequently, one patient developed a second local recurrence, one was lost to follow-up due to transfer to a different hospital, and three patients were alive with no recurrence.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ePatient characteristics and outcomes of cases with cancer recurrence\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePatient No.\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge at time of surgery (Years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e56\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e47\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e44\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgical procedure\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNSM\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNSM\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNSM\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNSM\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSSM\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCharacter of primary tumor\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSize\u003csup\u003ea\u003c/sup\u003e (mm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e67\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e54\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgical margin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.3mm\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eER/PR status\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+/+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+/+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+/+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+/+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+/+\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNuclear grade\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTND\u003csup\u003eb\u003c/sup\u003e (mm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTime to recurrence (Months)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e46\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e72\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDetection of tumor recurrence\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003elump\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003elump\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003elump\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLocation of tumor recurrence\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003esub-cutaneous\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eareola\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003elymph node\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003esub-cutaneous\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003esub-cutaneous\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePathology of recurring tumor\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDCIS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIDC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIDC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIDC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIDC\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTreatment for tumor recurrence\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgery\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRadiation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEndocrine therapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChemotherapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFollow-up after recurrence\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSecond recurrence\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTransfer to hospital\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlive\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"6\"\u003eNSM: nipple-sparing mastectomy, SSM: skin-sparing mastectomy, US: ultrasonography, DCIS: ductal carcinoma in situ, IDC: invasive ductal carcinoma, TND: tumor-nipple distance\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"6\"\u003e\u003csup\u003ea\u003c/sup\u003eSize: Lesion extent was measured by MRI.\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"6\"\u003e\u003csup\u003eb\u003c/sup\u003eTND: The minimum TND measured by MRI\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe Cox proportional hazards model showed no significant difference in the risk of local recurrence according to treatment choice, even after adjusting for age and BMI (hazard ratio [HR] for SM: 0 [0-inf], HR for SSM: 0.66 [0.07\u0026ndash;6.1]).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective cohort study of 245 patients who underwent mastectomy for DCIS examined the risk of local recurrence for three techniques: SM, SSM, and NSM. Four of the five patients who had recurrence underwent NSM, whereas the 5-year postoperative cumulative rates, compared using the log-rank test, showed no significant differences among the three groups. The pathology of the recurrent tumor was invasive recurrence in four of the five patients.\u003c/p\u003e \u003cp\u003eThere have been some reports on the long-term outcomes of NSM and SSM in patients with breast cancer, including DCIS [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The long-term outcomes of NSM and SSM have been shown to be as oncologically as safe as simple mastectomy. In previous studies focusing on the 10-year outcomes of DCIS, the 10-year local recurrence rate was 2.6% [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Previous studies on local recurrence rates of NSM and SSM for DCIS have reported rates of 4.5% [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] and 0.97% [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] at 10 years of follow-up. The results of our study were comparable to those of previous studies. Predictors of local recurrence in DCIS are tumor size, young age, high nuclear grade, negative hormone receptor and human epidermal growth factor receptor 2-positive, tumor necrosis, and surgical margins [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22 CR23\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. However, even after adjusting for age and BMI, the recurrence rate did not change in each group due to the small number of events, and it was not possible to examine the risk factors for recurrence in our study.\u003c/p\u003e \u003cp\u003eRegarding surgical indications, The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] states that the absence of breast cancer extension into the nipple or skin is the criterion for NSM or SSM. However, the methods for evaluating the absence of breast cancer extension into the nipple or skin vary between institutions. Previous studies have demonstrated that skin sparing is feasible from an oncological safety perspective when the distance between the tumor and dermis is \u0026gt;\u0026thinsp;2 mm on breast ultrasound. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] We do not have a specific criterion of 2 mm for the distance between the tumor and the skin in skin-sparing mastectomy.\u003c/p\u003e \u003cp\u003eRegarding the criteria for nipple-areola complex preservation, the indication for preserving the nipple-areola complex is defined as cases without abnormal nipple enhancement connected to the lesion on MRI. In a previous retrospective study from our institution, 11 of 404 patients who underwent NSM for breast cancer had local recurrence (median follow-up of 61 months); two patients had recurrence at the conserved nipple-areola complex [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Previous single-center cohort studies reported the NSM criterion as 2 cm from the nipple-areola complex based on preoperative imaging [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The new National Comprehensive Cancer Network (NCCN) guidelines [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] presented NSM criteria of 1 cm from the nipple-areola complex, and other recent matched cohort studies have shown that, even when the tumor-nipple distance (TND) is less than 1 cm on imaging, oncological safety is not different from the group with a TND greater than 1 cm [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In our institution, patients are candidates for NSM if they have no clinical findings, that is, no bloody nipple discharge, no Paget disease, and no infiltration within the nipple on MRI. A negative result on a routine intraoperative subareolar biopsy was an indication for NSM, and TND was not considered. It seems that the eligibility criteria for NSM and SSM at our hospital are acceptable.\u003c/p\u003e \u003cp\u003eBreast MRI is a recommended method for diagnosing the spread of breast cancer, as studies indicate its effectiveness in detecting DCIS, surpassing the sensitivity of mammography [\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Moreover, it is particularly valuable in assessing nipple involvement to identify potential candidates for nipple-sparing mastectomy (NSM) [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe utilization of breast MRI not only improves the detection of breast cancer spread and DCIS compared to mammography, but also serves as a crucial tool for evaluating nipple involvement and determining eligibility for NSM. The integration of MRI into surgical decision-making processes holds the potential to expand eligibility for both NSM and SSM.\u003c/p\u003e \u003cp\u003eOur study had several limitations. We only assessed whether the type of mastectomy was a risk factor for DCIS recurrence. The relationship between DCIS subtypes based on molecular biomarkers (e.g., ER, PR, and HER2 status) and the risk of recurrence could not be analyzed. A short follow-up period of 5 years may also have underestimated the occurrence of recurrence. In our series, four of the five cases of recurrence involved invasive cancers. Patients who experience recurrence after mastectomy for DCIS are more likely to have an advanced recurrence than those who experience recurrence after breast conservation surgery, suggesting they may have a higher-risk profile [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. We will continue to follow patients and analyze the association between local control and the risk of recurrence for long-term results. Further studies are also needed to follow up after treatment for recurrent tumors and compare prognoses, including distant metastasis-free survival and overall survival.\u003c/p\u003e \u003cp\u003eIn conclusion, in our single-center, retrospective study, SSM and NSM showed oncological safety for DCIS that was comparable to that of conventional mastectomy. Preoperative breast ultrasound and MRI, in addition to mammography, are useful in determining the surgical approach.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflict of Interest\u003c/h2\u003e\n\u003cp\u003eThe authors declare no conflicts of interest associated with this research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWard EM, DeSantis CE, Lin CC, Kramer JL, Jemal A, Kohler B, et al. Cancer statistics: Breast cancer in situ. CA Cancer J Clin. 2015;65:481\u0026ndash;95. https://doi.org/10.3322/caac.21321\u003c/li\u003e\n\u003cli\u003eTada K, Kumamaru H, Miyata H, Asaga S, Iijima K, Ogo E, et al. Characteristics of female breast cancer in Japan: Annual report of the National Clinical Database in 2018. Breast Cancer. 2023;30:157\u0026ndash;66. https://doi.org/10.1007/s12282-022-01423-4\u003c/li\u003e\n\u003cli\u003eKubo M, Kumamaru H, Isozumi U, Miyashita M, Nagahashi M, Kadoya T, et al. Annual report of the Japanese Breast Cancer Society registry for 2016. Breast Cancer. 2020;27:511\u0026ndash;8. https://doi.org/10.1007/s12282-020-01081-4\u003c/li\u003e\n\u003cli\u003eHayashi N, Kumamaru H, Isozumi U, Aogi K, Asaga S, Iijima K, et al. Annual report of the Japanese Breast Cancer Registry for 2017. Breast Cancer. 2020;27:803\u0026ndash;9. https://doi.org/10.1007/s12282-020-01139-3\u003c/li\u003e\n\u003cli\u003eKurebayashi J, Miyoshi Y, Ishikawa T, Saji S, Sugie T, Suzuki T, et al. Clinicopathological characteristics of breast cancer and trends in the management of breast cancer patients in Japan: Based on the Breast Cancer Registry of the Japanese Breast Cancer Society between 2004 and 2011. Breast Cancer. 2015;22:235\u0026ndash;44. https://doi.org/10.1007/s12282-015-0599-6\u003c/li\u003e\n\u003cli\u003eBadve SS, G\u0026ouml;kmen-Polar Y. Ductal carcinoma in situ of breast: Update 2019. 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Breast Cancer. 2016;23:851\u0026ndash;60. https://doi.org/10.1007/s12282-015-0651-6\u003c/li\u003e\n\u003cli\u003eSakurai T, Zhang N, Suzuma T, Umemura T, Yoshimura G, Sakurai T, et al. Long-term follow-up of nipple-sparing mastectomy without radiotherapy: A single center study at a Japanese institution. Med Oncol. 2013;30:481. https://doi.org/10.1007/s12032-013-0481-3\u003c/li\u003e\n\u003cli\u003eStuart KE, Houssami N, Taylor R, Hayen A, Boyages J. Long-term outcomes of ductal carcinoma in situ of the breast: A systematic review, meta-analysis and meta-regression analysis. BMC Cancer. 2015;15:890. https://doi.org/10.1186/s12885-015-1904-7\u003c/li\u003e\n\u003cli\u003eWu ZY, Kim HJ, Lee J, Chung IY, Kim JS, Lee SB, et al. Recurrence outcomes after nipple-sparing mastectomy and immediate breast reconstruction in patients with pure ductal carcinoma in situ. Ann Surg Oncol. 2020;27:1627\u0026ndash;35. https://doi.org/10.1245/s10434-019-08184-z\u003c/li\u003e\n\u003cli\u003eLhenaff M, Tunon de Lara C, Fournier M, Charitansky H, Brouste V, Mathoulin-Pelissier S, et al. A single-center study on total mastectomy versus skin-sparing mastectomy in case of pure ductal carcinoma in situ of the breast. Eur J Surg Oncol. 2019;45:950\u0026ndash;5. https://doi.org/10.1016/j.ejso.2019.01.014\u003c/li\u003e\n\u003cli\u003eTimbrell S, Al-Himdani S, Shaw O, Tan K, Morris J, Bundred N. Comparison of local recurrence after simple and skin-sparing mastectomy performed in patients with ductal carcinoma in situ. Ann Surg Oncol. 2017;24:1071\u0026ndash;6. https://doi.org/10.1245/s10434-016-5673-6\u003c/li\u003e\n\u003cli\u003eCarlson GW, Page A, Johnson E, Nicholson K, Styblo TM, Wood WC. Local recurrence of ductal carcinoma in situ after skin-sparing mastectomy. J Am Coll Surg. 2007;204:1074\u0026ndash;8; discussion 1078\u0026ndash;80. https://doi.org/10.1016/j.jamcollsurg.2007.01.063\u003c/li\u003e\n\u003cli\u003eFitzsullivan E, Lari SA, Smith B, Caudle AS, Krishnamurthy S, Lucci A, et al. Incidence and consequence of close margins in patients with ductal carcinoma-in situ treated with mastectomy: Is further therapy warranted? Ann Surg Oncol. 2013;20:4103\u0026ndash;12. https://doi.org/10.1245/s10434-013-3194-0\u003c/li\u003e\n\u003cli\u003eLago V, Maisto V, Gimenez-Climent J, Vila J, Vazquez C, Estevan R. Nipple-sparing mastectomy as treatment for patients with ductal carcinoma in situ: A 10-year follow-up study. Breast J. 2018;24:298\u0026ndash;303. https://doi.org/10.1111/tbj.12947\u003c/li\u003e\n\u003cli\u003eFujii T, Nakazawa Y, Ogino M, Obayashi S, Yajima R, Honda C, et al. Oncological safety of immediate breast reconstruction with skin- or nipple-sparing mastectomy: The value of tumor-to-dermis distance measured by preoperative ultrasonography. World J Surg Oncol. 2021;19:72. https://doi.org/10.1186/s12957-021-02185-7\u003c/li\u003e\n\u003cli\u003eGalimberti V, Vicini E, Corso G, Morigi C, Fontana S, Sacchini V, et al. Nipple-sparing and skin-sparing mastectomy: Review of aims, oncological safety and contraindications. Breast. 2017;34;Suppl 1:S82\u0026ndash;4. https://doi.org/10.1016/j.breast.2017.06.034\u003c/li\u003e\n\u003cli\u003eLecl\u0026egrave;re FM, Panet-Spallina J, Kolb F, Garbay JR, Mazouni C, Leduey A, et al. Nipple-sparing mastectomy and immediate reconstruction in ductal carcinoma in situ: A critical assessment with 41 patients. Aesthetic Plast Surg. 2014;38:338\u0026ndash;43. https://doi.org/10.1007/s00266-013-0236-8\u003c/li\u003e\n\u003cli\u003eGradishar WJ, Moran MS, Abraham J, et al. Breast cancer. version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw; 2022;20:p. 691\u0026ndash;722\u003c/li\u003e\n\u003cli\u003eWu ZY, Kim HJ, Lee J, Chung IY, Kim J, Lee SB, et al. Oncologic safety of nipple-sparing mastectomy in patients with breast cancer and tumor-to-nipple distance \u0026le;\u0026thinsp;1 cm: A matched cohort study. Ann Surg Oncol. 2021;28:4284\u0026ndash;91. https://doi.org/10.1245/s10434-020-09427-0\u003c/li\u003e\n\u003cli\u003eMann RM, Kuhl CK, Kinkel K, Boetes C. Breast MRI: Guidelines from the European Society of Breast Imaging. Eur Radiol. 2008;18:1307\u0026ndash;18. https://doi.org/10.1007/s00330-008-0863-7\u003c/li\u003e\n\u003cli\u003eBaur A, Bahrs SD, Speck S, Wietek BM, Kr\u0026auml;mer B, Vogel U, et al. Breast MRI of pure ductal carcinoma in situ: Sensitivity of diagnosis and influence of lesion characteristics. Eur J Radiol. 2013;82:1731\u0026ndash;7. https://doi.org/10.1016/j.ejrad.2013.05.002\u003c/li\u003e\n\u003cli\u003eKuhl CK, Schrading S, Bieling HB, Wardelmann E, Leutner CC, Koenig R, et al. MRI for diagnosis of pure ductal carcinoma in situ: A prospective observational study. Lancet. 2007;370:485\u0026ndash;92. https://doi.org/10.1016/S0140-6736(07)61232-X\u003c/li\u003e\n\u003cli\u003eLee SC, Mendez-Broomberg K, Eacobacci K, Vincoff NS, Gupta E, McElligott SE. Nipple-sparing mastectomy: What the radiologist should know. RadioGraphics. 2022;42:321\u0026ndash;39. https://doi.org/10.1148/rg.210136\u003c/li\u003e\n\u003cli\u003ePawloski KR, Tadros AB, Sevilimedu V, Newman A, Gentile L, Zabor EC, et al. Patterns of invasive recurrence among patients originally treated for ductal carcinoma in situ by breast-conserving surgery versus mastectomy. Breast Cancer Res Treat. 2021;186:617\u0026ndash;24. https://doi.org/10.1007/s10549-021-06129-3\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"breast-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brca","sideBox":"Learn more about [Breast Cancer](http://link.springer.com/journal/12282)","snPcode":"12282","submissionUrl":"https://www.editorialmanager.com/brca/default2.aspx","title":"Breast Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"nipple-sparing mastectomy (NSM), skin-sparing mastectomy (SSM), simple mastectomy (SM), ductal carcinoma in situ (DCIS), local recurrence","lastPublishedDoi":"10.21203/rs.3.rs-3901814/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3901814/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIn invasive breast cancer, there is no difference in mid- and long-term oncological safety results between nipple-sparing mastectomy (NSM), skin-sparing mastectomy (SSM) and simple mastectomy (SM). However, there are few reports on ductal carcinoma in situ (DCIS). This study aimed to compare the local recurrence and survival rates of the three techniques (NSM, SSM, and SM) in Japanese patients undergoing mastectomy for DCIS.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePatients undergoing NSM, SSM, and SM at our institution between 2006 and 2015 were identified, and their outcomes were analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe mean follow-up period was 80.4 months (standard deviation [SD]: 37.1 months). NSM was performed in 152 cases, SSM in 49, and SM in 44. Five of 245 patients developed local recurrences. Four of these patients had invasive cancer. The primary endpoints of 5-year cumulative local recurrence were 2.4% (95% confidence interval [CI]: 0.0\u0026ndash;5.0) for NSM, 2.2% (95% CI: 0.0\u0026ndash;6.3) for SSM, and 0% (95% CI: 0.0\u0026ndash;0.0) for SM. There were no significant differences in the 5-year local recurrence rate.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn conclusion, in our single-center, retrospective study, SSM and NSM showed oncological safety for DCIS that was comparable to that of conventional simple mastectomy.\u003c/p\u003e","manuscriptTitle":"Comparison of locoregional recurrence risk among nipple-sparing mastectomy, skin-sparing mastectomy, and simple mastectomy in patients with ductal carcinoma in situ: A single-center study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-06 17:49:08","doi":"10.21203/rs.3.rs-3901814/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-02-04T14:38:01+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-02-04T12:41:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-31T14:44:55+00:00","index":"","fulltext":""},{"type":"submitted","content":"Breast Cancer","date":"2024-01-30T09:48:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"breast-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brca","sideBox":"Learn more about [Breast Cancer](http://link.springer.com/journal/12282)","snPcode":"12282","submissionUrl":"https://www.editorialmanager.com/brca/default2.aspx","title":"Breast Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"dddc34f9-3f1a-4104-801d-f8073215c293","owner":[],"postedDate":"February 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-01T16:15:30+00:00","versionOfRecord":{"articleIdentity":"rs-3901814","link":"https://doi.org/10.1007/s12282-024-01613-2","journal":{"identity":"breast-cancer","isVorOnly":false,"title":"Breast Cancer"},"publishedOn":"2024-07-17 16:05:01","publishedOnDateReadable":"July 17th, 2024"},"versionCreatedAt":"2024-02-06 17:49:08","video":"","vorDoi":"10.1007/s12282-024-01613-2","vorDoiUrl":"https://doi.org/10.1007/s12282-024-01613-2","workflowStages":[]},"version":"v1","identity":"rs-3901814","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3901814","identity":"rs-3901814","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}