Therapeutic Nipple-sparing Mastectomy Research Articles

Intraoperative frozen section of subareolar tissue in nipple-sparing mastectomy: Towards a less is more approach

BackgroundNipple preservation contributes to aesthetic outcome and quality of life in women undergoing Skin-Sparing Mastectomy (SSM) with immediate breast reconstruction for the treatment of breast cancer. Intraoperative Frozen Section (IFS) has been advocated to facilitate conversion from Nipple-Sparing Mastectomy (NSM) to SSM in cases with positive subareolar margins. This study investigated the application of IFS at our comprehensive cancer centre. MethodsIn this single-centre retrospective study, for all patients who underwent therapeutic NSM with IFS from 2000 to 2021 pathological reports, patient- and tumour characteristics were retrieved. ResultsIn total 640 women were included in whom 662 intended NSMs with IFS had been performed. Sensitivity and specificity of frozen section compared with definitive histopathology were 75.2% and 98.5% respectively. In six women with a false positive result, the nipple had been removed. In 16 out of 32 women with a false negative result, the nipple was excised in a second procedure. In total 115 nipples were resected. In 40% of these nipples, no residual disease was detected. DiscussionIFS is a moderately sensitive and highly specific diagnostic tool to detect positive subareolar margins. An alternative approach is to omit frozen section but take intraoperative biopsies of the sub areolar margin, which are postoperatively analysed with definitive formalin-fixed paraffin-embedded histopathology. This allows for shared decision making regarding nipple excision in cases where minimal disease is found in subareolar tissue or cases with an indication for post-mastectomy radiotherapy.

Expanded Indications for Nipple-Sparing Mastectomy and Immediate Breast Reconstruction in Patients Older Than 60 Years.

Although nipple-sparing mastectomy (NSM) and immediate breast reconstruction (IBR) have long been praised for excellent cosmetic results and the resultant psychosocial benefits, the feasibility and safety of these procedures in patients older than 60 years have yet to be demonstrated in a large population. Patients undergoing NSM with or without IBR at the MedStar Georgetown University Hospital between 1998 and 2017 were included. Patient demographics, surgical intervention, and complication and recurrence events were retrieved from electronic medical records. Primary outcomes were recurrence and complication rates by age groups older and younger than 60 years. There were 673 breasts from 397 patients; 58 (8.6%) older than 60 years and 615 (91.4%) younger than 60 years with mean follow-up of 5.43 (0.12) years. The mean age for those older than 60 was 63.9 (3.3) years, whereas that for those younger than 60 was 43.1 (7.9) years (P < 0.001). The older than 60 group had significantly higher prevalence of diabetes, rates of therapeutic (vs prophylactic) and unilateral (vs bilateral) NSM, and mastectomy weight. However, there were no significant differences by age group in complication rates or increased risk of locoregional or distant recurrence with age. Based on similar complication profiles in both age groups, we demonstrate safety and feasibility of both NSM and IBR in the aging population. Despite increased age and comorbidity status, appropriately selected older women were able to achieve similar outcomes to younger women undergoing NSM with or without IBR.

Low rate of complications in nipple-sparing mastectomy for patients with BRCA1 and BRCA2 mutation.

Background: To describe the indications and outcomes of BRCA mutation carriers undergoing nipple-sparing mastectomy (NSM). Methods: In this retrospective study, 76 BRCA mutation carriers with no cancer who opted to undergo risk reduction NSM or diagnosed with breast cancer (BC) who opted to undergo therapeutic NSM were included. Results: Indications for NSM: cancer treatment (n=33), bilateral risk reduction (n=39) and contralateral prophylactic NSM (n=4). In a mean follow-up of 45months (median: 30months), one patient (2.5%) undergoing risk-reducing NSM developed a new BC. One (3%) local, one (3%) ipsilateral axillary and one (3%) distant recurrence were observed in BC patients. No partial or total nipple necrosis occurred. Conclusion: NSM is safe for reducing the risk of BC development in BRCA mutation carriers and for treating cancer.

Literature review and guide for optimal position in implant-based breast reconstruction.

Identification of ideal candidates for prepectoral versus retropectoral implant-based breast reconstruction relies on careful preoperative risk assessment and intraoperative flap evaluation. Few guidelines exist to guide the surgeon's decision-making process when evaluating the preferred plane for implant placement. A literature review was performed to develop clinical decision-making algorithms for direct-to-implant (DTI) reconstruction with acellular dermal matrix (ADM) for patients undergoing prophylactic or therapeutic nipple-sparing mastectomy (NSM) based on patient characteristics, surgical techniques, and outcomes. Prepectoral reconstruction is most suitable for patients with small breasts or macromastia with desire for breast reduction, low-grade ptosis, smaller implant sizes, those undergoing PMRT, and for those who aim to mitigate animation deformity and capsular contracture. Retropectoral reconstruction may be recommended for patients with larger breasts with no desire for size change requiring additional prosthesis support, and in patients who aim to reduce likelihood of rippling and need for subsequent fat grafting procedures to address contour abnormalities. Careful preoperative and intraoperative assessment of reconstruction options for patients undergoing implant-based breast reconstruction is necessary to mitigate complications and produce superior aesthetic outcomes. Decision algorithms may be used to determine ideal surgical techniques based on patient factors, like radiation history and planning, breast size and ptosis, and patient preferences.

Dermal Nipple-Areola Complex Perfusion through Circumareolar Scars: A Delay Model in Two-Stage Nipple-Sparing Mastectomy.

Nipple-sparing mastectomy (NSM) has evolved as a standard surgical option. The NSM complication rate remains high in large breasts. To reduce the risk of necrosis, several authors have proposed delayed procedures to enhance blood supply to the nipple-areola complex (NAC). The purpose of this study in a porcine model was to show adequate redirection of NAC perfusion by neoangiogenesis through circumareolar scars. Delayed two-staged NSM was simulated in 52 nipples (six pigs) with a 60-day interval. The nipples underwent a full-thickness, circumareolar incision onto the muscular fascia, with preservation of underlying glandular perforators. After 60 days, NSM was performed through a radial incision. A silicone sheet was introduced in the mastectomy plane to prevent NAC revascularization by wound bed imbibition. Digital color imaging was used to assess necrosis. Near-infrared fluorescence with indocyanine green was used to assess perfusion patterns and perfusion in real time. No NAC necrosis was seen after 60 days' delay in any nipples. In all nipples, indocyanine green angiography showed complete alteration of the NAC vascular perfusion pattern from subjacent gland to a capillary fill following devascularization, exhibiting a predominant arteriolar capillary blush without distinct larger vessels. NAC delay reverses glandular perfusion to adequate dermal neovascularization. Neovascularization through full-thickness scars provides sufficient dermal perfusion after 60 days' delay. Identical staged delay in humans may be a surgically safe NSM option and could broaden therapeutic NSM indications in difficult breasts. Large clinical trials are necessary to provide identical results in human breasts. NAC delay reverses glandular perfusion to adequate dermal neovascularization. Neovascularization through full-thickness scars provides sufficient dermal perfusion after 60 days of delay. Identical staged delay in humans may be a surgically safe NSM option.

Long-Term Cancer Recurrence Rates following Nipple-Sparing Mastectomy: A 10-Year Follow-Up Study.

Despite the increased use of nipple-sparing mastectomies, there are limited data examining long-term cancer recurrence rates in these patients. The objective of this study was to analyze breast cancer recurrence in patients who underwent therapeutic nipple-sparing mastectomy with a median of 10 years of follow-up. All patients undergoing nipple-sparing mastectomy at a single institution were retrospectively reviewed temporally to obtain a median of 10 years of follow-up. Patient demographic factors, mastectomy specimen pathologic findings, and oncologic outcomes were analyzed. Univariate analysis was performed to identify independent risk factors for locoregional recurrence. One hundred twenty-six therapeutic nipple-sparing mastectomies were performed on 120 patients. The most frequently observed tumor histology included invasive ductal carcinoma (48.4 percent) and ductal carcinoma in situ (38.1 percent). Mean tumor size was 1.62 cm. Multifocal or multicentric disease and lymphovascular invasion were present in 31.0 percent and 10.3 percent of nipple-sparing mastectomy specimens, respectively. Sentinel lymph node biopsy was performed in 84.9 percent of nipple-sparing mastectomies, and 17.8 percent were positive. The rate of positive frozen subareolar biopsy was 7.3 percent ( n = 82) and that of permanent subareolar pathology was 9.5 percent ( n = 126). The most frequently observed pathologic tumor stages were stage I (44.6 percent) and stage 0 (33.9 percent). The incidence of recurrent disease was 3.17 percent per mastectomy and 3.33 percent per patient. On univariate analysis, no demographic, operative, or tumor-specific variables were independent risk factors for locoregional recurrence. Overall recurrence rates are low in patients undergoing nipple-sparing mastectomy at a median follow-up of 10-years. Close surveillance should remain a goal for patients and their providers to promptly identify potential recurrence. Risk, III.

PC20. LONG-TERM CANCER RECURRENCE RATES FOLLOWING NIPPLE-SPARING MASTECTOMY: A 10-YEAR FOLLOW UP STUDY

PURPOSE: Although nipple-sparing mastectomy (NSM) is a widely accepted and popular technique, limited data exists examining long-term cancer recurrence rates associated with it. This study sought to analyze rates of breast cancer recurrence in patients who underwent therapeutic NSM with a median of 10 years of follow-up. METHODS: A single institution retrospective review identified all patients who underwent NSM with a median of 10-years of follow-up. Analysis focused on patient demographics, mastectomy specimen pathology, and oncologic outcomes including cancer recurrence. Independent risk factors for locoregional recurrence were assessed via univariate logistic regression. RESULTS: 158 therapeutic NSMs were performed on 152 patients. Invasive ductal carcinoma (48.7%) and ductal carcinoma in situ (35.4%) were the most common tumor types seen on pathology. Multifocal/multicentric disease and lymphovascular invasion were present in 34.1% and 12.8% of specimens, respectively. Sentinel lymph node biopsy rate was 82.9%, with 15.2% reported as positive. Rates of positive frozen and permanent subareolar biopsy were 5.4% and 8.3%, respectively. Low cancer stages were overwhelmingly more common, with stage I and stage 0 representing 40.5% and 35.4% of the population, respectively. Incidence of recurrent disease was 3.2% per mastectomy and 3.3% per patient. Univariate analysis did not identify any variables that were independent risk factors for locoregional recurrence. CONCLUSION: At a median of 10 years of follow-up, overall cancer recurrence rates are low in patients who undergo NSM, further suggesting the safety of this technique. Regardless, close surveillance should remain a goal to ensure prompt detection of any sign of recurrence.

Staged breast reconstruction before nipple-sparing mastectomy with reconstruction

: Since the introduction of the radical mastectomy, surgical treatment for breast cancer has evolved significantly including advancements in breast reconstruction, resulting in improvements in both oncologic and aesthetic outcomes. Nipple-sparing mastectomy (NSM), in which the nipple-areolar complex is preserved along with skin, has become an oncological option for several groups of patients including patients with low body mass index (BMI), minimal ptosis, small breasts and non-smokers. Recently, patients who were initially deemed poor candidates for this procedure—such as women with macromastia or high-grade ptosis—have undergone NSM and reconstruction with successful outcomes due to the utilization of staged surgical techniques. In this review, options for staging reconstruction after mastectomy are outlined for both therapeutic and prophylactic NSMs. For therapeutic mastectomies, patients may undergo breast envelope shaping with either reduction mammoplasty, mastopexy, or oncoplastic reconstruction in a first stage, followed later by NSM and definitive reconstruction. Alternatively, NSM can be completed in the initial stage either with or without immediate breast reconstruction, followed by breast envelope shaping in a later stage. For prophylactic mastectomies, similar strategies may be employed with either breast envelope shaping or NSM up-front. Here, strategies for the various staging approaches are reviewed along with several techniques for nipple delay, and an algorithm for treatment of these patients is proposed.

Predicting Nipple–Areolar Complex Necrosis in Nipple-sparing Mastectomy with a Machine Learning Model

BACKGROUND & OBJECTIVES: Necrosis of the nipple-areolar complex (NAC) is the Achilles’ heel of Nipple Sparing Mastectomy (NSM).1 Our goal was to create a user-friendly, validated technology platform that surgeons could utilize preoperatively to predict which patients are at risk of NAC necrosis and aid in shared decision-making. This prediction would be based on patient characteristics and intraoperative variables. METHODS: We conducted a retrospective review of all NSM with immediate reconstruction performed at our institution between January 2015 and July 2019. Preoperative clinical characteristics, operative variables, and postoperative complications were collected and linked to NAC outcomes. These results were utilized to train a Random Forest machine learning model to predict necrosis when given preoperative patient characteristics, including age, BMI, smoking status, medical history, previous breast incisions, breast size, and planned implant or tissue expander (TE) size. Our model was subsequently validated by predicting NAC outcomes in a prospective cohort. The prospective cohort included all therapeutic and prophylactic NSM performed at our institution from May 2020 through October 2020. RESULTS: 305 breasts in 181 patients were included in the retrospective dataset which served as the foundation for our machine learning model. Full-thickness skin necrosis including part or all of the NAC occurred in 46 cases (15.1%). The strongest predictors of NAC necrosis were implant weight (P < 0.001) and weight of the mastectomy specimen (P < 0.001). When controlling for implant volume in our model, fill weight maintained a strong association with NAC necrosis. Rates of NAC necrosis among TE reconstructions using air only were lower at equivalent volumes compared with TE using saline fill and direct to implant reconstructions. Other influential factors included diabetes (P = 0.005), smoking (P = 0.04), and hypertension (= 0.03). With a prospective cohort of 27 patients, our predictive machine learning model achieved 96% accuracy (P = 0.02) with high positive predictive value and specificity for NAC necrosis. The model correctly predicted 4 of 5 cases of NAC necrosis and all 22 cases without necrosis. CONCLUSIONS: Implant weight is an independent risk factor for NAC necrosis following NSM, indicating that lower implant volumes, or using air-only initial TE fill, may mitigate the risk of NAC necrosis. The findings of our predictive Random Forest machine learning model also provide a basis for utilizing artificial intelligence to predict cases with a high probability of NAC necrosis. We created an easy-to-use interface for our model, which allows a user to input patient characteristics and receive a prediction which includes a binary outcome: “NAC Necrosis” or “No NAC Necrosis” and the predicted probability of necrosis. The instrument also provides a description of each variable’s effect on the prediction. Such models may be developed using institutional data and utilized to inform patient decision-making prior to mastectomy. REFERENCE: 1. Wapnir I, Dua M, Kieryn A, et al. Intraoperative imaging of nipple perfusion patterns and ischemic complications in nipple-sparing mastectomies. Ann Surg Oncol. 2014;21(1):100–106.

Subareolar Tissue Biopsy Predicts Occult Nipple Involvement in Nipple-Sparing Mastectomies.

Subareolar tissue is examined during nipple-sparing mastectomy (NSM) to minimize the risk of occult malignancy within the preserved nipple. A positive subareolar tissue biopsy typically warrants subsequent nipple excision. We study the factors associated with a positive subareolar tissue biopsy, the rate of residual malignancy in subsequent nipple excisions, and the value of subareolar tissue biopsy intraoperative frozen section (IOF). We identified 1,026 consecutive NSMs with separately submitted subareolar tissue biopsies over a 5.5-year period. Clinicopathologic data were reviewed. We examined concordance rates between subareolar tissue biopsy and subsequent nipple excisions as well as IOF diagnosis and permanent control diagnosis. Among cases of therapeutic NSM, the rate of a positive subareolar tissue biopsy was 7.2%. Multifocal/multicentric disease (P = .0005), presence of lymphovascular invasion (P = .033), and nodal involvement (P = .006) were significantly associated with a positive subareolar tissue biopsy. Thirty-nine of 41 cases with positive subareolar biopsies underwent subsequent nipple excision, with 20 (51%) showing residual carcinoma. Among all IOF samples, 9 (3.3%) showed a discrepancy between the IOF and permanent diagnoses, mostly because of false-negatives. A positive subareolar tissue biopsy predicts residual carcinoma in the excised nipples in 51% of cases. IOF is accurate and reliable.

How Protective are Nipple-Sparing Prophylactic Mastectomies in BRCA1 and BRCA2 Mutation Carriers?

Nipple-sparing mastectomy (NSM) is now routinely offered to BRCA mutation carriers for risk reduction. We assessed the rates of ipsilateral cancer events after prophylactic and therapeutic NSM in BRCA1 and BRCA2 mutation carriers. BRCA1 and BRCA2 mutation carriers undergoing NSM from October 2007 to June 2019 were identified in a single-institution prospective database, with variants of unknown significance being excluded. Patient, tumor, and outcomes data were collected. Follow-up analysis was by cumulative breast-years (total years of follow-up of each breast) and woman-years (total years of follow-up of each woman). Overall, 307 BRCA1 and BRCA2 mutation carriers (160 BRCA1, mean age 41.4years [range 21-65]; and 147 BRCA2, mean age 43.8years [range 23-65]) underwent 607 NSMs, with a median follow-up of 42 months (range 1-143). 388 bilateral prophylactic NSMs had 744 cumulative woman-years of follow-up, with no new cancers seen (< 0.0013 new cancers per woman-years); 251 BRCA1 prophylactic NSMs had 1034 cumulative breast-years of follow-up, with no new ipsilateral cancers seen (< 0.0010 per breast-year); 66 BRCA1 therapeutic NSMs had 328 cumulative breast-years of follow-up, with one ipsilateral cancer recurrence not directly involving the nipple or areola (0.0030 per breast-year); 237 BRCA2 prophylactic NSMs had 926 cumulative breast-years of follow-up, with no new ipsilateral cancers seen (< 0.0011 per breast-year); and 53 BRCA2 therapeutic NSMs had 239 cumulative breast-years of follow-up, with two ipsilateral recurrent cancers, neither of which directly involved the nipple or areola (0.0084 per breast-year). The risk of new ipsilateral breast cancers is extremely low after NSM in BRCA1 and BRCA2 mutation carriers. NSM is an effective risk-reducing strategy for BRCA gene mutations.

Oncologic Safety of Nipple-Sparing Mastectomy for Patients with Breast Cancer

In patients undergoing mastectomy, benefits of nipple preservation include improved esthetics and quality of life. The purpose of this review is to evaluate the oncologic safety of nipple-sparing mastectomy (NSM) in women with breast cancer, focusing on complications, recurrence, and patient reported outcomes. Clinical presentation, risk factors for nipple involvement, and preoperative imaging may be helpful in choosing appropriate candidates. Recent series suggest that complications after NSM are slightly increased when compared to traditional mastectomy but likely related to increased risk of nipple necrosis. Pathologic assessment of the nipple is necessary. Local recurrence after NSM appears similar to patients after traditional mastectomy; however, studies evaluating local recurrence are of lower quality and have short follow-up. NSM is associated with improved psychosocial and sexual well-being after surgery. Studies evaluating oncologic safety of therapeutic NSM suggest that it is a viable option for appropriate patients, as risk of local recurrence and survival appears to be similar to patients undergoing traditional mastectomy. However, careful patient selection is critical.

Postoperative complications following simultaneous therapeutic and contralateral prophylactic nipple-sparing mastectomy: a retrospective study

Introduction: Nipple-Sparing Mastectomy (NSM) is increasingly indicated for therapeutic and prophylactic purposes due to better cosmetic results with nipple maintenance. Postoperative complications have not been compared among patients who have undergone simultaneous therapeutic and contralateral prophylactic NSM. The aim of the present study was to evaluate the incidence and risk factors for postoperative complications in bilateral/unilateral NSMs, and therapeutic and/or prophylactic NSMs. Methods: Retrospective study of patients who underwent NSM between 2007 and 2017 at A.C. Camargo Cancer Center. Results: Among 290 patients, 367 NSMs were performed, 64 simultaneous therapeutic and contralateral prophylactic NSM. The latter were associated with more postoperative complications (OR=3.42; p=0.002), mainly skin flap necrosis (OR=3.79; p=0.004), hematoma (OR=7.1; p=0.002), wound infection (OR=3.45; p=0.012), and nipple-areola complex (NAC) loss (OR=9.63; p=0.003). Of the 367 NSMs, 213 were unilateral NSMs, which were associated with lower rates of postoperative complications (OR=0.44; p=0.003), especially skin flap necrosis (OR=0.32; p=0.001), hematoma (OR=0.29; p=0.008), wound infection (OR=0.22; p=0.0001), and reoperation (OR=0.38; p=0.008). Obesity was related to more postoperative complications (OR=2.55; p=0.01), mainly hematoma (OR=3.54; p=0.016), reoperation (OR=2.68; p=0.023), and NAC loss (OR=3.54; p=0.016). Patients’ age (p=0.169), their smoking status (p=0.138), breast ptosis (0.189), previous chest radiotherapy (p 1), or previous breast surgery (p=0.338) were not related to higher chances of postoperative complications. Conclusions: Results suggest that performing therapeutic and contralateral prophylactic NSM as separated procedures may represent a good strategy for minimizing postoperative complications.

Tumor-to-nipple Distance Should Not Preclude Nipple-sparing Mastectomy in Breast Cancer Patients. Personal Experience and Literature Review.

A retrospective study was performed in 246 breast cancer patients to define whether tumor-to-nipple distance (TND) assessment by breast MRI may select patients eligible to nipple-sparing mastectomy (NSM) as compared to permanent section assessment of retroareolar margin. Pre- and post-operative parameters including imaging data, histology of the primary tumor, biologic prognostic factors, and adjuvant regimens were retrieved; patients with close/positive retroareolar margins underwent nipple or NAC excision. The primary endpoint was loco-regional recurrence (LRR). Patients with TND ≤2 cm had a significantly higher rate of invasive ductal carcinoma (p<0.003) and excision margins less than 2 mm (p<0.000). Eleven retroareolar specimens were positive at definitive pathology; final re-excision specimen examination showed residual disease in seven patients (63.6%). At a median follow-up of 31 to 33 months, no NAC recurrence did occur; disease-free survival was more than 96%, and LRR was homogeneously distributed among TND subgroups. Therapeutic NSM is a safe procedure independently of TND assessed at preoperative breast MRI. Permanent section assessment of retroareolar tissue is more accurate and cost-effective than frozen section. Furthermore, delayed nipple and/or NAC excision did not impair local disease control.

Increase in Utilization of Nipple-Sparing Mastectomy for Breast Cancer: Indications, Complications, and Oncologic Outcomes.

Nipple-sparing mastectomy (NSM) is increasingly performed for invasive breast cancer. Growing evidence supporting the oncologic safety of NSM has led to its widespread use and broadened indications. In this study, we examine the indications, complications, and long-term outcomes of therapeutic NSM. From 2003 to 2016, women undergoing NSM for invasive cancer or ductal carcinoma in situ (DCIS) were identified from a prospectively maintained database. Patient and disease characteristics were compared by procedure year, while complications were compared by procedure year using generalized mixed-effects models accounting for a random surgeon effect. Overall survival and time to recurrence were examined. Of the 467 therapeutic NSMs, 337 (72%) were invasive cancer, 126 (27%) were DCIS, and 4 (1%) were phyllodes tumors. Median age was 45years (range 24-75) and median follow-up among survivors was 39.4months. Three hundred and fifty-seven (76.4%) cases were performed in 2011 or after. When comparing NSMs performed before and after 2011, there was a significant increase in NSMs performed for invasive tumors (58% vs. 77%; p < 0.001). There was no difference in family history, genetic mutations, smoking status, neoadjuvant chemotherapy, prior radiation, nodal involvement, or tumor subtype. Twenty-one (4.5%) nipple excisions were performed, of which 14 were performed for cancer at the nipple margin. Forty-four breasts (9.4%) had complications that required re-operation. Fifteen patients had locoregional recurrence or distant metastasis. NSM use for invasive carcinoma has doubled at our institution since 2011, while postoperative complications and recurrence rates remain low. Our experience supports the selective use of NSM in the malignant setting with careful patient selection.

Breast Cancer Recurrence in the Nipple-Areola Complex After Nipple-Sparing Mastectomy With Immediate Breast Reconstruction for Invasive Breast Cancer

The main concern associated with nipple-sparing mastectomy (NSM) is the risk of local breast cancer recurrence at the retained nipple-areola complex (NAC) consequent to occult nipple involvement. Long-term follow-up data regarding the oncologic safety of modern therapeutic NSM in terms of cancer recurrence at the NAC and survival are limited. To assess the incidence, risk factors, treatment, and long-term outcomes associated with cancer recurrence at the NAC in a large series of patients with invasive breast cancer who underwent NSM and immediate breast reconstruction. In this retrospective cohort study at a single institution (Asan Medical Center) in Seoul, Republic of Korea, 962 breasts from 944 patients who underwent NSM and immediate breast reconstruction for invasive breast cancer were analyzed between March 3, 2003, and December 31, 2015. Patients who underwent neoadjuvant systemic therapy or palliative surgery were excluded. Data analysis was performed from June 4, 2018, to August 31, 2018. Univariate and multivariate Cox proportional hazards regression models were used to analyze the association between clinicopathologic variables and cancer recurrence at the NAC. To evaluate the association between cancer recurrence at the NAC and prognosis, distant metastasis-free survival, and overall survival were estimated using the Kaplan-Meier method and compared using the log-rank test. Among the 944 study patients (median age at diagnosis, 43 years [range, 23-67 years]) during a median follow-up of 85 months (range, 14-185 months), 39 cases (4.1%) of cancer recurrence at the NAC were identified as the first event after NSM. The 5-year cumulative incidence of cancer recurrence at the NAC was 3.5% (n = 34). In multivariate analyses, multifocality or multicentricity (hazard ratio [HR], 3.309; 95% CI, 1.501-7.294; P = .003), negative hormone receptor or ERBB2 (formerly HER2 or HER2/neu)-positive subtype (HR, 3.051; 95% CI, 1.194-7.796; P = .02), high histologic grade (HR, 2.641; 95% CI, 1.132-6.160; P = .03), and extensive intraductal component (HR, 3.338; 95% CI, 1.262-8.824; P = .02) were independently associated with cancer recurrence at the NAC after NSM. All 39 recurrent cases involved wide local excision. Patients with and without cancer recurrence at the NAC as the first event did not differ significantly with regard to distant metastasis-free survival (P = .95) or overall survival (P = .21). The 10-year distant metastasis-free survival rates were 89.3% among patients with cancer recurrence at the NAC and 94.3% among patients without recurrence. The 10-year overall survival rates were 100% among patients with cancer recurrence at the NAC and 94.5% among those without recurrence. Patients had a low incidence of cancer recurrence at the NAC after NSM and immediate breast reconstruction in this study. The findings suggest that multifocal or multicentric disease, hormone receptor-negative/ERBB2-positive subtype, high histologic grade, and positive extensive intraductal component should be considered before determining the NSM procedure.

Oncologic Trends, Outcomes, and Risk Factors for Locoregional Recurrence: An Analysis of Tumor-to-Nipple Distance and Critical Factors in Therapeutic Nipple-Sparing Mastectomy.

Oncologic outcomes with nipple-sparing mastectomy continue to be established. The authors examine oncologic trends, outcomes, and risk factors, including tumor-to-nipple distance, in therapeutic nipple-sparing mastectomies. Demographics, outcomes, and overall trends for all nipple-sparing mastectomies performed for a therapeutic indication from 2006 to 2017 were analyzed. Oncologic outcomes were investigated with specific focus on recurrence and associated factors, including tumor-to-nipple distance. A total of 496 therapeutic nipple-sparing mastectomies were performed, with an average follow-up time of 48.25 months. The most common tumor types were invasive carcinoma (52.4 percent) and ductal carcinoma in situ (50.4 percent). Sentinel lymph node sampling was performed in 79.8 percent of nipple-sparing mastectomies; 4.1 percent had positive frozen sentinel lymph node biopsy results, whereas 15.7 percent had positive nodal status on permanent pathologic examination. The most common pathologic cancer stage was stage IA (42.5 percent) followed by stage 0 (31.3 percent). The rate of local recurrence was 1.6 percent (n = 8), and the rate of regional recurrence was 0.6 percent (n = 3). In all, 171 nipple-sparing mastectomies had magnetic resonance imaging available with which to assess tumor-to-nipple distance. Tumor-to-nipple distance of 1 cm or less (25.0 percent versus 2.4 percent; p = 0.0031/p = 0.1129) and of 2 cm or less (8.7 percent versus 2.0 percent; p = 0.0218/p = 0.1345) trended to higher rates of locoregional recurrence. In univariate analysis, tumor-to-nipple distance of 1 cm or less was the only significant risk factor for recurrence (OR, 13.5833; p = 0.0385). No factors were significant in regression analysis. In early stage and in situ breast carcinoma, therapeutic nipple-sparing mastectomy appears oncologically safe, with a locoregional recurrence rate of 2.0 percent. Tumor-to-nipple distances of 1 cm or less and 2 cm or less trended to higher recurrence rates. Risk, III.

Discussion: Oncologic Trends, Outcomes, and Risk Factors for Locoregional Recurrence: An Analysis of Tumor-to-Nipple Distance and Critical Factors in Therapeutic Nipple-Sparing Mastectomy.

Discussion: Oncologic Trends, Outcomes, and Risk Factors for Locoregional Recurrence: An Analysis of Tumor-to-Nipple Distance and Critical Factors in Therapeutic Nipple-Sparing Mastectomy.

Oncologic safety of nipple-sparing mastectomy in patients with short tumor-nipple distance.

There is a tendency to avoid nipple-sparing mastectomy (NSM) when a tumor-nipple distance (TND) is <2cm due to the risk of occult nipple involvement. The purpose of the study was to determine whether the patients who undergo NSM with immediate reconstruction are oncologically safe when TND is <2cm. Patients who underwent NSM followed by immediate reconstruction for breast cancer were retrospectively analyzed. Patients who are negative for nipple-base in either frozen-section or paraffin histopathology were included. MRI was used to obtain TNDs to compare local-recurrence-free and disease-free survival in group I (TND <2cm) and group II (TND ≥2cm). Disease-free survival rates were determined to assess the outcome. Of the 214 cases with malignancy on MRI, 21 cases diagnosed with pure ductal carcinoma in situ were excluded. Among the 193 NSM cases diagnosed with invasive cancer, TND was <2.0cm in 59 (30.56%) cases and ≥2.0cm in 134 (69.43%) cases. No significant differences were found between groups in regards to ER, PR, HER2-neu status, and nodal involvement (P=0.34, P=0.41, P=0.54, and P=0.12 respectively). In a median follow-up time of 62months (range; 13-114), patients in group I had four local recurrences, whereas group II was found to have five local and three distant metastases. No significant differences were observed between groups concerning disease-free survival (10-year DFS 93.2% vs 96.3%; P=0.368 respectively). Patients who have invasive cancer diagnosis with a TND <2cm are eligible to undergo therapeutic NSM with immediate reconstruction.

Abstract P5-22-19: Nipple sparing mastectomy in unselect patients: Experience of an academic center in the south of Brazil

Abstract INTRODUCTION: Nipple sparing mastectomy (NSM) consists in the complete excision of the breast gland, mantaining the subcutaneous tissue, skin and nipple-areola complex (NAC). Recently, the NSM was developed as a therapeutic option not just for the patients that need risk-reducing surgery, but also for patients that have tumors not involving the NAC. OBJECTIVES: Evaluate the overall survival, disease-free survival and local recurrence of the patients that underwent NSM. The only exclusion criteria for NSM was lesion at the NAC. MATERIAL AND METHODS: Retrospective study that evaluate the number of cases of NSM performed between 2003 and 2015 in a private sector in the south of Brazil. RESULTS: A total of 224 patients underwent NSM during the period of 2003-2015. The mean age was 47 years. From the total, 43 patients underwent risk-reducing NSM and 181 therapeutic NSM (64 unilateral and 117 bilateral). In those cases of bilateral procedures all of them underwent risk-reducing surgery on the contralateral breast (there were no bilateral cancers). Of this 181 cases, 108 (59%) have familiar history of breast cancer, considering first, second and third-degree relatives. Twenty six patients (14%) have history of previous breast cancer diagnosed. In this group of 181 patients with therapeutic NSM, 29 (16%) developed any unfavorable outcomes, 13 (7%) local recurrence, 4 (2%) ipsilateral node recurrence, 3 (1,6%) contralateral recurrence and 9 (5%) distant metastasis. None of the local recurrences occurred at the NAC, neither the cited unfavorable outcomes occurred in the risk-reducing setting. In a median follow-up of 47,7 months, the overall survival was 95% (8 deaths related to breast cancer) and the disease-free survival was 83,7%. CONCLUSIONS: The overall survival rates of 95% at 47 months of follow-up is similar to the literature rates, that range from 93 to 97% in 5 years, depending on study's inclusion criterias. In our study, 14% of patients had previous breast cancer and 59% of patients treated for breast cancer by NSM had positive familiar history of breast cancer. This results in an unselected group of patients confirms the safety of this therapeutic method as an option for breast cancer patients. Citation Format: Frasson A, Zerwes F, Souza A, Rossato N, Miranda I, Trindade V, Vollbrecht B, Santos M, Viegas J. Nipple sparing mastectomy in unselect patients: Experience of an academic center in the south of Brazil [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-22-19.