Time Of Breast Conserving Surgery Research Articles

Abstract PS01-08: Management of ipsilateral breast tumor recurrence following breast conservation surgery for ductal carcinoma in situ – a data-free zone

Abstract Background: Breast-conserving surgery (BCS) is well established for the management of ductal carcinoma in situ (DCIS). Although a growing body of data support re-conservation therapy (RBCS) for ipsilateral breast tumor recurrence (IBTR) following BCS in invasive cancer, neither randomized trials nor guidelines address management of IBTR following BCS for DCIS. Here we aim to compare the outcomes of mastectomy vs RBCS for a large series of DCIS patients with IBTR. Methods: We identified women treated with BCS for DCIS at MSKCC who developed IBTR as a first event. Between those treated with mastectomy vs RBCS, we compared the clinicopathologic characteristics for the initial and recurrent tumors, the use of adjuvant RT (both upfront (“primary RT”) and post IBTR (“secondary RT”)) and/or tamoxifen, the rate of third events (local, regional, distant), breast cancer specific (BCSS) and overall survival (OS). Results: From our service databases among 3001 women treated with BCS for DCIS (1978-2010), we found 383 who developed an IBTR as a first event and were treated at our institution between 1983-2023, 186 (49%) with RBCS and 197 (51%) with mastectomy. RBCS was more frequent over time and comprised 56% of patients treated between 2014 and 2023. Among those treated with mastectomy, the initial tumors were significantly more likely to have necrosis (74% vs 59%), high grade (47% vs 28%), comedo histology (38% vs 20%), and to have received primary RT at the time of BCS (61% vs 21%). Between those who underwent mastectomy vs RBCS, there were no significant differences in disease-free interval, in the pathologic characteristics of their IBTR, or in the proportion of invasive vs in situ disease. For patients treated with RBCS, 11 (5.9%) received both primary and secondary RT and 77 (41.3%) received neither (Table 1a). For patients treated with a mastectomy only 8.5% had secondary RT (Table 1b). At a median follow-up of 5.1 years post-IBTR, third local events in total were more frequent for RBCS vs mastectomy (16.1% vs 3.0%, 0.001), but there were no differences in BCSS or OS. Among RBCS patients, third local events (breast re-recurrence) were least frequent among those who received primary and secondary RT, and comparable between with who did vs did not receive secondary RT (16% (13/82) vs 16% (117/104), Table 2). Conclusions: Our data show that for women with isolated IBTR following BCS for DCIS and treated by mastectomy vs RBCS, 1) treatment with mastectomy was associated with less favorable initial pathology and more frequent use of primary RT, 2) re-recurrence was more frequent with RBCS, and 3) BCSS and OS were comparable. In an era of increasing surgical de-escalation, our data suggest a wider role for RBCS and – as for patients having RBCS for IBTR following invasive cancer – further study of the relationship between secondary RT and the rate of third breast events. Citation Format: Brian Diskin, Varadan Sevilimedu, Kimberly Van Zee, Monica Morrow, Hiram Cody. Management of ipsilateral breast tumor recurrence following breast conservation surgery for ductal carcinoma in situ – a data-free zone [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS01-08.

Intra-Operative Radiotherapy (IORT) in Breast Conserving Therapy in Early-Stage Breast Cancer and DCIS

Initial breast intra-operative radiotherapy (IORT) results in clinical trials were encouraging though with longer follow up, increased local recurrences have been reported compared with whole breast radiation or other partial breast radiation including accelerated partial breast irradiation (APBI) methods. The goal of the study is to report our prospective single institution IORT breast study outcomes of local recurrence (LR) including true recurrence and breast elsewhere failures, breast cancer specific survival (BCSS), and overall survival (OS) with low energy x-ray IORT in early-stage breast cancer or ductal carcinoma in situ. A total of 480 patients with early-stage breast cancer or DCIS were prospectively enrolled in an IRB approved single institution trial and treated with low energy X-ray IORT 20 Gy at time of breast-conserving surgery. Eligibility criteria included ≥ 45 years of age with unifocal tumors < 3 cm deemed candidates for partial mastectomy. Supplemental external beam radiation was recommended for patients with high-risk surgical pathology including multifocal disease, positive nodes, close margins < 2 mm, or lymphovascular invasion. Ipsilateral breast tumor recurrences were classified as true recurrence versus elsewhere failure by location and histology: same/different quadrant and similar/different histology. Kaplan-Meier methods were used to estimate survival probabilities across time. Median age of enrolled patients was 64 years with the majority of patients having favorable phenotype with 94% ER+ and 93% Her-2 - disease. 110 patients (23%) had supplemental EBRT delivered; 103 to the whole breast and 7 to the breast and regional nodes. At a median follow up of 73 months (range 17 - 131 months), there were 23 (4.8%) ipsilateral breast tumor recurrences, of which 9 were true recurrences (1.9%) and 14 elsewhere failures (2.9%). One patient with true recurrence and 3 patients with elsewhere breast failures synchronously presented with clinical or radiographic regional node involvement. Seven patient developed contralateral breast cancer and 8 patients developed distant metastases during the follow-up period. There were 2 breast cancer related deaths. At 6-years, overall survival rate was 96.8% and breast cancer specific survival was 98.7%. Our study outcomes reflect similar outcomes as other reported IORT studies with electron or low energy X-ray in breast cancer, with higher risk of local failure than historical whole breast and other partial breast radiation techniques. This supports current radiation society guidelines for IORT monotherapy for breast cancer to be optimally considered in the context of prospective clinical trials.

Magseed placement before neoadjuvant chemotherapy to facilitate subsequent breast-conserving surgery – a single-centre audit

BACKGROUND: A radio-opaque clip is placed in all patients planned for breast-conserving surgery (BCS) receiving neoadjuvant chemotherapy (NACT) to localise the tumour bed in case response to chemotherapy makes later localisation impossible. A tumour that was localised with a radio-opaque clip before NACT will then need a second localisation procedure, after the completion of NACT to aid BCS. The two most commonly used methods are hookwire and radio-guided occult lesion localisation. Magseed®, a newly available technology consisting of a small magnetic seed, has now become available. The seed is placed instead of a radio-opaque clip before the start of or during NACT and can remain in place until the time of BCS. METHODS: A retrospective cohort study was performed, collecting data on patients who had a Magseed placed before or during NACT from December 2018 to February 2020. RESULTS: Twenty-one Magseed devices were placed into the breasts of 20 patients, 18 under ultrasound guidance, and three under stereotactic guidance. The average breast volume of individuals who had seeds placed was 1 532 g ± 869 g. The duration that the seeds were in situ was 138 days ± 45 days. All preoperatively placed seeds were retrieved at the surgery with no observed migration outside the tumour bed. CONCLUSION: Magseed placement before NACT is a safe and technically simple technique that can be done under ultrasound guidance in the majority of cases. It has the advantage of being a single procedure with an associated reduction in time off work and travel cost to the patient, as well as flexibility in terms of the time of placement.

Partial Breast Reirradiation for Patients With Ipsilateral Breast Tumor Recurrence After Initial Treatment With Breast Conservation for Early Stage Breast Cancer

PurposeAccelerated partial breast irradiation (APBI), including intraoperative radiation therapy (IORT), is an evidence-based treatment option in patients undergoing breast conserving surgery (BCS) for early-stage breast cancer. However, literature regarding reirradiation for patients with ipsilateral breast tumor recurrences (IBTR) is limited. This prospective study assessed the feasibility and efficacy of using APBI in patients who had prior whole breast irradiation. Methods and MaterialsThis was a single institution, prospective study of patients who were previously treated with BCS and adjuvant whole breast radiation. At the time of enrollment, all had unifocal IBTR, histologically confirmed invasive ductal carcinoma with negative margins after repeat BCS. Patients received either IORT in a single fraction at time of BCS or MammoSite brachytherapy twice daily over 5 days. Follow-up data and patient surveys were collected at 1, 3, 6, 9, and 12 months, then annually for at least a 5-year period. ResultsFrom 2008 to 2014, 13 patients were enrolled. Median time to recurrence after initial course of radiation was 12.5 years. Median follow-up after retreatment was 7.8 years. One patient in the IORT group had a subsequent tumor bed recurrence, yielding a local control of 92%. One patient had distant recurrence. At baseline, 680 reported excellent-good cosmesis compared with 42% at 5 years. All patients indicated total satisfaction with overall treatment experience. ConclusionsAPBI using IORT was well tolerated with excellent local control and may be a reasonable alternative to mastectomy for IBTR. Further study is needed to determine the most suitable candidates for this approach.

Abstract P3-19-12: Impact of endocrine therapy (ET) noncompliance following intra-operative radiation therapy (IORT) in treatment of early-stage breast cancer patients (pts) enrolled in the ExBRT trial

Abstract Purpose: To investigate the association between ET noncompliance and ipsilateral breast tumor recurrence (IBTR) in the ExBRT trial (“A Safety and Efficacy Study of Intra-Operative Radiation Therapy [IORT] Using the Xoft® Axxent® Electronic Brachytherapy [eBx®] System at the Time of Breast Conservation Surgery for Early-Stage Breast Cancer”). Methods: The IRB-approved single arm prospective nonrandomized multi-institutional ExBRT trial was designed to determine the efficacy and outcome of a single 20 Gy fraction of IORT delivered at the time of lumpectomy for early-stage breast cancer. The trial included women age ≥ 40 years with invasive ductal carcinoma (IDC) or ductal carcinoma in situ (DCIS) of all molecular subtypes documented by pre-operative biopsy which were ≤ 30 mm by clinical and radiographic evaluation. Tumors with pre-operative lymphovascular invasion and intra-operative positive lymph nodes and/or margins were excluded. ET was defined as treatment with tamoxifen, anastrozole, letrozole, and/or exemestane. Pts were classified as “Compliant with ET” if they completed a 60-month ET course or were compliant with ongoing ET. Pts were defined as “Discontinued ET” if they stopped ET prior to completing a 60-month ET course. Pts were classified as “Declined ET” if they did not initiate recommended ET. Data, collected at enrollment and at 1, 6, 12, 18 and 24 months, then yearly, included demographics, histopathology, estrogen receptor positivity (ER+), progesterone receptor positivity (PR+), adjuvant therapy, IBTR, and survival. The primary endpoint was IBTR. Preliminary results evaluating the impact of ET noncompliance on pts who successfully completed treatment with a single 20 Gy fraction of IORT per protocol are presented. Results: Between May 2012 - July 2018, 1105 pts (mean age 64 years) with pre-operative biopsy-proven IDC or DCIS successfully completed a single fraction of IORT treatment per protocol. Mean follow-up was 4.0 years (range 2-8 years). One-hundred fifteen (10%) pts, who were either ER negative or had an unknown ER status, are not included in this analysis. Pt cohorts and tumor characteristics are presented in Table 1. There were 39 (3.93%) IBTR in the ER+ subset at mean follow-up of 4 years. IBTR in the “Compliant with ET” group was 2.53%. Although the percentages were greater in the “Discontinued ET” (5.68%) and “Declined ET” (7.10%) cohorts, this did not reach statistical significance (Chi square test, p-value = 0.147). Conclusion: IORT allows pts to conveniently receive both their surgery and electronic brachytherapy radiation treatment in one setting. Early-stage ER+ breast cancer pts compliant with a subsequent course of ET in this study experienced a lower IBTR rate, improving the collective outcome of their multidisciplinary treatment. These preliminary ExBRT trial results demonstrate that IBTR rates are improved with ET compliance. Although this has not reached statistical significance in this trial, it may partially explain the slight differences in IBTR rates noted in comparison with similar electronic brachytherapy early-stage breast cancer studies. Table 1.IORT pt cohorts and tumor characteristicsCompliant with ETDiscontinued ETDeclined ETNNNER +631176183PR +597170162Mean age (years)65.766.366.7Postmenopausal580162161Mean tumor size (mm)11.110.712.7Tumor HistologyIDC524136120grade I2116055grade II2535955grade III54159Unknown grade621DCIS933756Low grade2099Intermediate grade421925High grade30922Unknown grade100Infiltrating lobular ca505Other932Chemotherapy given4286Ethnicity/RaceCaucasian498143151African American351013Hispanic46188Asian/Pacific Islander2812Native American211Other2238Recurrences16 (2.53%)10 (5.68%)13 (7.10%) Citation Format: Barbara Schwartzberg, AMNisar Syed, Robert Cohen, William Dooley, Maen Farha, Veronica Jones, Wesley Hodge. Impact of endocrine therapy (ET) noncompliance following intra-operative radiation therapy (IORT) in treatment of early-stage breast cancer patients (pts) enrolled in the ExBRT trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-12.

Atypical Hyperplasia at the Margin of Frozen Sections from Breast-Conserving Surgery

Purpose: Intraoperative frozen section analysis to assess margin status during breast-conserving surgery is often performed to reduce the rate of re-excision. Whether additional resection is required if atypical cells are found at the margin during breast-conserving surgery is controversial. The aim of this study was to evaluate the accuracy of intraoperative frozen section analysis and investigate the feasibility of additional resection in cases of atypical hyperplasia on frozen sections from breast-conserving surgery.Methods: A retrospective analysis was performed on 1,411 patients with invasive breast cancer who underwent breast-conserving surgery between July 2004 and June 2012. The microscopic margins of the intraoperative frozen sections and permanent sections were examined. Overall events (locoregional recurrence and distant metastasis) were analyzed between the negative margin group and the other margin group (including atypical hyperplasia, carcinoma in situ [CIS], and invasive carcinoma).Results: Of the 1,411 patients, 1,201 had negative margins and 210 had other margin types in the first frozen section. 68 patients had atypical hyperplasia on frozen section analysis. This atypical hyperplasia included atypical cells, atypical ductal hyperplasia, and atypical lobular hyperplasia. Of these 68 patients, the final findings on the permanent section were negative (n=32, 47.1%), atypical cells (n=16, 23.5%), and CIS (n=20, 29.4%). The rate of overall events and distant metastases were higher in the other margin group (9.5% vs. 5.4%, p=0.021) and (5.7% vs. 3.0%, p=0.045). Of the 1,411 patients, 44 (3.1%) had false-positive findings, and 15 (1.1%) had false-negative findings in the frozen sections, with an accuracy of 95.8%.Conclusion: The accuracy of intraoperative frozen section analysis was 95.8%, with 91.7% sensitivity and 96.4% specificity. Atypical hyperplasia on frozen section analysis requires additional resection at the time of breast-conserving surgery because of the possibility of CIS, but excessive resection may be performed in other cases. Therefore, sufficient consultation with patients is required.

De-Escalation of Radiation Therapy in Patients with cT1-T2 (< 3 cm) N0 HER2+ Breast Cancer Treated With Neoadjuvant Systemic Therapy With Pathologic Complete Response at the Time of Breast Conserving Surgery

The excellent survival and locoregional outcomes from the APT trial in predominantly stage I HER2+ breast cancer (BC) treated with upfront surgery (∼75% breast conservation surgery [BCS]) and adjuvant paclitaxel/trastuzumab has raised optimism that radiation (RT) may be de-escalated in this setting. Our initial analysis using the National Cancer Database (NCDB) instead demonstrated an association between RT omission and worse overall survival (OS) in these patients. Patients with HER2+ disease that receive neoadjuvant systemic therapy (NST) demonstrate great outcomes for patients with a pathologic complete response (pCR). This suggests that pCR may be used to de-escalate RT in early-stage HER2+ patients treated with NST+BCS. We used the NCDB to test the hypothesis that RT omission results in equivalent OS in cT1-2 (< 3 cm) N0 HER2+ patients treated with NST+BCS with pCR.We identified patients with cT1-T2 (< 3 cm) N0 HER2+ BC treated with anti-HER2 based NST and BCS +/- RT from 2013-2015. We identified factors associated with RT omission using logistic regression analysis. We evaluated OS in the subset of patients with pCR stratified by receipt of RT. We used a propensity score matched (PSM) analysis to compare OS between the groups. Patients were matched on clinical and demographic factors. The effect of RT omission was evaluated with a Cox proportional hazards model with robust standard errors to account for clustering in matched pairs.We identified 4,842 patients (4,505 RT; 337 no RT): 31.7% ER-/PR-; 48.5% with pCR. On multivariate analysis, age≥70 (OR = 2.88, P < 0.0001), Black race (OR = 1.43, P = 0.03), and use of single-agent cytotoxic chemotherapy (OR = 1.47, P = 0.02) were associated with RT omission. There was a trend towards RT omission in patients with pCR (OR = 1.21, P = 0.11). OS data was available in 1,581 (1,471 RT; 110 no RT) of the 2,348 patients with pCR. Median follow-up was 27.1 months (IQR = 19.7-37.0 months) with 14 deaths (3 RT; 11 RT omission). The 2-year OS was significantly worse for patients with RT omission (96.9% vs. 99.7%, P = 0.02). The PSM cohort consisted of 103 (of a possible 110) pairs of patients with 6 deaths (3 RT; 3 RT omission) and median follow-up 25.6 months (IQR, 17.9-35.9 months). In the PSM cohort, RT omission was not significantly associated with an increased risk of death (2-year OS 96.7% vs. 98.5%; HR = 1.12, 95% CI 0.23-5.41, P = 0.89).We did not find an association between RT omission and increased risk of death in patients with cT1-T2 (< 3 cm) N0 HER2+ BC treated with NST+BCS with pCR. Patients that did not receive RT tended to be older, of Black race, and to have received single-agent cytotoxic chemotherapy. These data support prospective evaluation of RT omission in this patient population in a randomized controlled trial.

Rates of margin positive resection with breast conservation for invasive breast cancer using the NCDB

BackgroundPrevious studies suggest the rate of positive surgical margin (PSM) after lumpectomy for breast cancer is approximately 20 %. The risk of PSM at time of resection is often a source of fear for patients, driving some to elect to undergo mastectomy. This study describes rates and predictors of positive margins for invasive breast cancers in the National Cancer Database (NCDB). Materials and methodsFrom 2004 to 2013, patients with non-metastatic invasive breast cancers who underwent breast conservation surgery were identified from the NCDB. Patients’ demographic, clinical, and facility of treatment characteristics were collected and compared. Per SSO-ASTRO-ASCO criteria, margin negative is defined as no gross or microscopic disease (i.e. no tumor on ink). Bivariate tests and multivariate logistic regression were conducted to identify independent predictors of patients with PSM at the time of resection. ResultsA total of 707,798 patients were identified with non-metastatic invasive breast tumors who underwent lumpectomy. Rate of PSM across the entire cohort was 5.02 %. Over time, the rate of PSM decreased significantly from 6.54 % in 2004 to 3.91 % in 2013 (p < 0.001). Pure lobular histology predicted for the highest rate of PSM compared with IDC (8.63 vs 4.55 %; p < 0.001). In adjusted analysis, high grade, non-ductal histology and HER2 amplification were significantly associated with PSM with breast conservation while estrogen and progesterone status were not. ConclusionThis study demonstrates a 5 % risk of PSM at time of breast conservation surgery using a large, modern national database. Patients with invasive lobular and mixed histology have a nearly two-fold risk of PSM compared to invasive ductal cancers. These results provide important data points to help appropriately counsel patients regarding the risk of PSM.

Abstract PS1-49: The effect of oncoplastic reduction on the incidence of post-operative breast lymphedema in breast cancer patients undergoing lumpectomy

Abstract Purpose / Objectives: In patients with macromastia, breast conservation surgery (BCS) followed by radiation therapy (RT) for the treatment of breast cancer may be associated with a different complication profile than those without macromastia. General complications of BCS followed by RT includes seroma, infection, wound complications, cosmetic deformity, asymmetry, acute versus long term arm and/or breast lymphedema. Oncoplastic reduction mammoplasty (ORM) aims to reduce breast volume while excising the tumor bed and its margins. Since breast volume was found to be a risk factor for chronic breast lymphedema, this study was performed to determine the impact of ORM on chronic breast lymphedema as well as other complications compared to BCS without ORM. Materials / Methods: We performed a retrospective chart review on patients who underwent lumpectomy with RT from 2014 to 2018. Chronic breast lymphedema (CBL) was defined as swelling that persisted &amp;gt;1 year post-RT. Breast volumes (BV) were determined by contoured breast volumes or, if unavailable, estimated by the 95% isodose volumes from the RT treatment planning system. Univariate analysis was used to evaluate various patient factors and treatment outcomes in women with BV ≥1300 cc compared to &amp;lt;1300 cc. These same factors were compared in women who underwent ORM vs. BCS alone. Multivariate regression analysis was used to evaluate factors associated with ≥1 complication. Logistic regression was performed to identify factors associated with the development of CBL. Results: The total population included 1173 patients, of which 51 (4.3%) underwent ORM and 1122 (95.7%) underwent BCS. 440 (37.5%) patients had BV ≥1300 cc and 733 (62.5%) patients had a BV &amp;lt;1300 cc. Multivariate regression analysis demonstrated that patients with BV ≥1300 cc had a higher BMI (OR=1.200, P&amp;lt;0.001), decreased risk of grade 2 radiation dermatitis (OR=0.457, P=0.002), and increased risk of CBL (OR=2.127, P=0.024) compared to patients with BV &amp;lt;1300 cc. However, oncoplastic reduction was associated with an increased risk of hematoma (OR=5.934, P&amp;lt;0.001), increased risk of wound dehiscence (OR=12.433, P&amp;lt;0.001), and decreased risk of seroma (OR=0.201, P&amp;lt;0.001) compared to BCS patients. Conclusions: Our data demonstrates that patients with breast volume &amp;gt; 1300 cc are at increased risk for developing several complications regardless of the presence of ORM. Those who had ORM experienced an increase in wound complications but having undergone ORM appeared to eliminate the increased risk of CBL associated with macromastia. This suggests that ORM should be considered at the time of BCS to reduce their future risk of CBL as there is no cure for this disease. Citation Format: Jenna Nicole Luker, Cara Canella, Sanjay Rama, Kelley Park, Renee Barry, Saheli Ghosh, Simeng Zhu, Yalei Chen, Jessica Bensenhaver, Eleanor Walker, Kenneth Levin, Maristella Evangelista, Dunya Atisha. The effect of oncoplastic reduction on the incidence of post-operative breast lymphedema in breast cancer patients undergoing lumpectomy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-49.

Breast-conserving surgery with 3D-printed surgical guide: a single-center, prospective clinical study

To facilitate precise tumor resection at the time of breast-conserving surgery (BCS), we developed and implemented a magnetic resonance imaging (MRI)-based three-dimensional-printed (3DP) breast surgical guide (BSG). This prospective cohort study was conducted at a single institution from July 2017 to February 2019 on women with breast cancer who underwent partial breast resection using patient-specific 3DP BSGs. Eighty-eight patients with invasive cancer were enrolled, of whom 1 patient had bilateral breast cancer. The mean size of the tumor long-axis on MRI before surgery was 2.8 ± 0.9 cm, and multiple tumors were observed in 34 patients. In 16 cases (18.0%), the resection margin was tumor-positive according to intraoperative frozen biopsy; all of these tumors were ductal carcinoma in situ and were re-excised intraoperatively. In 93.3% of the cases, the resection margin was tumor-free in the permanent pathology. The mean pathological tumor size was 1.7 ± 1.0 cm, and the mean distance from the tumor to the border was 1.5 ± 1.0 cm. This exploratory study showed that the tumor area on the MRI could be directly displayed on the breast when using a 3DP BSG for BCS, thereby allowing precise surgery and safe tumor removal.Trial Registration Clinical Research Information Service (CRIS) Identifier (No. KCT0002375, KCT0003043).

The Effect of Oncoplastic Reduction on The Incidence of Post-Operative Lymphedema in Breast Cancer Patients Undergoing Lumpectomy

In patients with macromastia, breast conservation surgery (BCS) followed by radiation therapy (RT) may be associated with increased radiation exposure and a different complication profile than those without macromastia. The oncoplastic reduction mammoplasty (ORM) procedure includes breast reduction at the time of BCS. The purpose of this study is to determine if women with macromastia who undergo ORM have a different complication profile compared to those who undergo BCS followed by RT. We performed a retrospective chart review on patients who underwent lumpectomy with RT from 2014 to 2017. Chronic breast lymphedema (CBL) was defined as swelling that persisted >1-year post-RT. Breast volumes (BV) were determined by contoured breast volumes or, if unavailable, estimated by the 95% isodose volumes from the RT treatment planning system. Univariate analysis was used to evaluate various patient factors and treatment outcomes in women with BV ≥1300 cc compared to <1300 cc. These same factors were compared in women who underwent ORM vs. BCS. Multivariate regression analysis was used to evaluate factors associated with ≥1 complication. Logistic regression was performed to identify factors associated with the development of CBL. The total population included 785 patients, of which 28 (3.6%) underwent ORM and 757 (96.4%) underwent BCS. The total population was stratified into two groups, in which 289 (36.8%) patients had BV ≥1300 cc and 496 (63.2%) patients had a BV <1300 cc. Compared to patients with BV<1300 cc, those with BV ≥1300 cc had a higher percentage of African Americans (52.6% vs. 41.5%, P = 0.002), higher median BMI (34.96 vs. 27.87, P<0.001), higher incidence of diabetes (39.8% vs. 27.2%, P<0.001), higher incidence of hypertension (75.4% vs. 63.1%, P<0.001), and higher incidence of CBL (12.5% vs. 4.2%, P<0.001). Compared to BCS patients, ORM patients with BV ≥1300 cc had increased incidence of CBL (36.4% vs. 11.5%, P = 0.035). Logistic regression showed that the incidence of ≥1 complication was associated with BMI, presence of SLNB, and the number of lymph nodes removed in either SLNB or ALND. However, factors such as ORM and BV were not associated with an increased risk of ≥1 complication. Logistic regression demonstrated that having a BV ≥1300 cc was associated with 2.5 times increased odds of CBL compared to those with BV <1300 cc. Even though those who underwent ORM did not change the risk for CBL for the entire cohort, ORM patients with BV ≥1300 had a higher risk of CBL. Ultimately, logistic regression demonstrates that ORM does not increase the risk of CBL when adjusting for BV. In conclusion, axillary surgery contributed most significantly to the incidence of having ≥1 complication. However, BV was associated with an increased risk of CBL, regardless of the presence of ORM. Therefore, women with BV ≥1300 cc should be offered ORM at the time of lumpectomy in order to reduce their future risk of CBL.

Oncologic safety of immediate autologous fat grafting for reconstruction in breast-conserving surgery.

Autologous fat grafting (AFG), or lipofilling, has been used for immediate reconstruction at the time of breast-conserving surgery in order to achieve a satisfactory cosmetic outcome in patients with breast cancer and an unfavorable tumor-to-breast volume ratio or unfavorable tumor location. However, the oncologic safety of this technique is still unclear. To determine whether AFG performed simultaneously with breast-conserving surgery is associated with differences in local relapse rates and disease-free survival. Matched retrospective cohort study. Tertiary referral center. Patients undergoing breast-conserving surgery with or without AFG between 2004 and 2016 were retrospectively enrolled and matched for age, staging, grade, tumor histology, and tumor immunohistochemical profile. The cumulative incidence of locoregional recurrence (LRR) and disease-free survival were the primary end points, while distant recurrence and overall survival were the secondary end points. A total of 320 patients were followed. Cases were matched with controls at a 1:4 ratio. There was no difference in LRR or distant recurrence of breast cancer between the two groups. The annual LRR rate was 0.86% in patients who received immediate AFG vs. 0.7% in patients undergoing breast-conserving surgery alone (p ≥ 0.05). Number of lymph nodes was the sole independent risk factor for local recurrence (p = 0.045). No significant differences in disease-free survival rates were found between the groups. At a mean follow-up of 5years, no significant differences in locoregional recurrence rates were found between patients who received immediate AFG and those who underwent breast-conserving surgery alone. These findings corroborate previous research demonstrating the oncological safety of immediate AFG reconstruction, further suggesting that this technique as a safe, effective way to achieve optimal cosmetic outcomes in primary breast cancer surgery without jeopardizing oncologic outcomes.

Breast conserving surgery with targeted intraoperative radiotherapy for the management of ductal carcinoma in situ.

A prospective randomized controlled trial has established the efficacy of targeted intraoperative radiotherapy (TARGIT) in the management of invasive breast cancer treated with breast-conserving surgery (BCS). The purpose of this analysis is to evaluate the efficacy of TARGIT in the management of ductal carcinoma in situ (DCIS). A prospective nonrandomized trial was designed to evaluate the success of TARGIT in the management of DCIS, as measured by a low risk of requiring additional surgery or radiotherapy and an acceptable local recurrence rate (LRR). Fifty-five patients with DCIS received BCS and TARGIT from November 2007 to March 2017. Median patient age was 57 years (range, 42-83 years) and median histological lesion size was 14.4 mm (range, 2-51 mm). Four patients required either re-excision and/or whole breast irradiation, yielding a rate of additional therapy of 7.3% (4 of 55). Among 46 women administered TARGIT at the time of initial BCS, two local recurrences were observed yielding a 4.3% (2 of 46) LRR at 46 months median follow-up (range, 4-116 months). There were no clinically significant adverse events. Preliminary evidence indicates TARGIT can be performed with a low risk of requiring additional therapy (7.3%) and an acceptable LRR (4.3%) when administered at the time of BCS.

Technique and Preliminary Results of a Multi-Center Trial of Intra-Operative Radiation Therapy Using Electronic Brachytherapy at the Time of Breast Conserving Surgery for Early Stage Breast Cancer

Technique and Preliminary Results of a Multi-Center Trial of Intra-Operative Radiation Therapy Using Electronic Brachytherapy at the Time of Breast Conserving Surgery for Early Stage Breast Cancer

(OA27) Outcome in Patients Treated With Partial Breast Reconstruction or Bilateral Reduction Mammoplasty at the Time of Breast Conserving Surgery (BCS) Followed by Whole Breast Radiation Therapy (WBRT)

Lumpectomy/ partial mastectomy may result in asymmetry of the treated breast relative to the unaffected breast. Volume loss is the most common cause of the negative cosmetic outcome in patients undergoing BCS. To help improve cosmetic results the practice of breast oncoplasty at the time of lumpectomy ± sentinel node surgery is gaining popularity. In this paper, we report our experience on patients who underwent autologous flap partial breast reconstruction or bilateral reduction mammoplasty at the time of BCS. Postoperatively, all patients received WBRT. The objective of the study was to evaluate cosmetic outcomes and local control. In addition, we sought to study the incidence for the recommendations of BIRADS 3 or 4, and fat necrosis on follow up mammograms and sonograms. In this retrospective study, we identified 24 breast cancer patients who at the time of BCS either underwent partial breast reconstruction using autologous flap or had bilateral reduction mammoplasty. Postoperatively, all patients received WBRT to a dose ranging from 50.4Gy to 60Gy. Adjuvant systemic therapy was prescribed at the discretion of the treating oncologist. In follow up, all patients were seen at regular intervals by the multidisciplinary team, and mammograms and directed sonograms were obtained at scheduled intervals. A total of 27 breasts in 24 patients (3 bilateral) are included in this review. The median follow up is 48 months (range: 4 months to 79 months). The median age is 52 years (range: 29 to 71 years). The pathologic stage distribution was: 7 stage 0, 13 stage I, 5 stage II, and 2 had stage ypT0N0M0 having presented with clinical stage IIB and undergone BCS following neoadjuvant therapy. All but 1 patient had negative resections margins. The median number of excisions to achieve clear margins was 2 (range 1 to 3). Fifteen patients underwent bilateral reduction mammoplasty, while 9 had either thoracodorsal artery perforator flap (TDAP), lateral intercostal artery perforator flap (LICAP), or other autologous free flaps. Twenty patients also received systemic chemotherapy and/or hormonal therapy. Cosmetic results in the majority were excellent/very good. In follow up we observed that 4 patients underwent additional revisions for cosmetic indications; and 3 of the 4 patients were among those who had partial breast reconstruction using free-flaps. Follow up mammography noted recommendation of BIRADS 3 and 4 in 3/27 (11.1%) and 2/27 (7.4%) breasts, respectively. Additionally, 5/27 (18.5%) had radiographic evidence of fat necrosis. No patient has developed a local recurrence. In the multidisciplinary care of breast cancer the integration of plastic surgery procedures is increasingly gaining acceptance. We observed that partial breast reconstruction as an adjunct to BCS prior to WBRT results in excellent cosmetic result and local control. Radiographically, the incidence of fat necrosis was the most common finding and the recommendation for BIRADS 4 was low. In select cases, partial breast reconstruction at the time of BCS prior to WBRT may be a reasonable approach to offset the volume loss of an extensive lumpectomy.

Identification of Preoperative Magnetic Resonance Imaging Features Associated with Positive Resection Margins in Breast Cancer: A Retrospective Study.

ObjectiveTo determine which preoperative breast magnetic resonance imaging (MRI) findings and clinicopathologic features are associated with positive resection margins at the time of breast-conserving surgery (BCS) in patients with breast cancer.Materials and MethodsWe reviewed preoperative breast MRI and clinicopathologic features of 120 patients (mean age, 53.3 years; age range, 27–79 years) with breast cancer who had undergone BCS in 2015. Tumor size on MRI, multifocality, patterns of enhancing lesions (mass without non-mass enhancement [NME] vs. NME with or without mass), mass characteristics (shape, margin, internal enhancement characteristics), NME (distribution, internal enhancement patterns), and breast parenchymal enhancement (BPE; weak, strong) were analyzed. We also evaluated age, tumor size, histology, lymphovascular invasion, T stage, N stage, and hormonal receptors. Univariate and multivariate logistic regression analyses were used to determine the correlation between clinicopathological features, MRI findings, and positive resection margins.ResultsIn univariate analysis, tumor size on MRI, multifocality, NME with or without mass, and segmental distribution of NME were correlated with positive resection margins. Among the clinicopathological factors, tumor size of the invasive breast cancer and in situ components were significantly correlated with a positive resection margin. Multivariate analysis revealed that NME with or without mass was an independent predictor of positive resection margins (odds ratio [OR] = 7.00; p < 0.001). Strong BPE was a weak predictor of positive resection margins (OR = 2.59; p = 0.076).ConclusionNon-mass enhancement with or without mass is significantly associated with a positive resection margin in patients with breast cancer. In patients with NME, segmental distribution was significantly correlated with positive resection margins.

Electronic Brachytherapy at the Time of Breast Conservation Surgery for Early-Stage Breast Cancer: Early Follow-Up Results of a Nonrandomized, Multicenter Trial

To describe early follow-up results of a trial of single-fraction, intra-operative radiation therapy (IORT) delivered with an electronic brachytherapy system immediately following surgical resection for treatment of early-stage breast cancer. To date, 1,028 participants have been enrolled in this open label, single-arm, prospective, non-randomized trial at 28 hospitals in the USA (27) and Portugal (1). 1,023 participants with biopsy-proven ductal carcinoma in situ (DCIS) or invasive ductal carcinoma who met the inclusion criteria underwent lumpectomy followed by IORT to the lumpectomy cavity. A presterilized lead shield was placed on the chest wall and a balloon applicator suitable to the surgical bed was placed in the lumpectomy cavity and inflated with saline (30-75 cc). Balloon surface-to-skin distance of ≥ 1.0 cm was confirmed by ultrasound. Single-fraction IORT (20 Gy) was delivered at the balloon applicator surface with a mean radiation treatment time of 11.3 minutes. Following IORT, balloon was deflated and removed along with lead shielding, and surgical site was sutured. The prespecified primary outcome of this 10-year follow-up study is ipsilateral breast tumor recurrence at 5 years. Prespecified secondary outcomes include 10-year recurrence and cosmesis (Harvard Scale). Median follow-up time was 1.2 years with 320, 102, and 10 participants completing 2-, 3-, and 4-year follow-up, respectively. Mean age at enrollment was 66 years (range 41-93). 246 participants had DCIS and 777 had invasive ductal carcinoma. DCIS nuclear grades were high (82), intermediate (119), or low (45) with three identified as bilateral. Invasive cancers were Grade 1 (318) including two bilateral cases, Grade 2 (340) with one bilateral case, Grade 3 (105) with two bilateral cases, or no Grade (14). Mean tumor size was 12.01 ± 10.8 mm. Cosmesis was excellent in 100% of participants at 4-year follow-up and excellent to good in 94% and 91% of participants at 2- and 3-year follow-up, respectively. The number of reported adverse events (AEs) that were Grade 2 or higher was 169 (9%). Seroma, breast induration, erythema, breast fibrosis, and breast pain were the most frequent AEs. There were ten deaths, none of which were breast cancer related. There were six ipsilateral breast recurrences and three new contralateral breast cancers. Single-fraction IORT using an electronic brachytherapy system following breast conservation surgery may be a promising treatment option for select early-stage breast cancer patients. Early findings from this multicenter trial suggest that the short and convenient course of radiation therapy has low morbidity, excellent to good cosmetic results, and a low rate of high-grade adverse events and recurrences.

Abstract P1-10-19: Two-year follow-up results of a multi-center trial of intra-operative electronic brachytherapy during breast conservation surgery for early stage breast cancer

Abstract Objective To assess the safety and efficacy of single-fraction, intra-operative radiation therapy (IORT) delivered with the Xoft® Axxent® Electronic Brachytherapy System® (eBx®) immediately following surgical resection for treatment of early stage breast cancer. Methods This phase 4, open-label, single-arm, prospective, non-randomized trial is still enrolling participants and is currently being conducted at 26 hospitals in the USA (25) and Portugal (1). 878 participants with biopsy-proven ductal carcinoma in situ (DCIS) or invasive ductal carcinoma who met the inclusion criteria underwent lumpectomy followed by single-fraction IORT to the lumpectomy cavity. Briefly, a small, presterilized lead shield piece was placed on the chest wall to reduce the dose to the ribs, and then a balloon applicator, suitable to the surgical bed, was placed in the lumpectomy cavity and inflated with saline (30-75 cc); skin was temporarily closed over the balloon and ultrasound was used to confirm a balloon surface-to-skin distance ≥ 1.0 cm. The Xoft System was used to deliver the 20 Gy dose at the balloon applicator surface. The balloon was deflated, lead shield and balloon removed and the surgical site sutured. The prespecified primary outcome of this 10-year follow-up study is recurrence of ipsilateral breast tumor at 5 years. Prespecified secondary outcomes include 10-year recurrence and cosmesis (Harvard Scale). Trial Registry: ClinicalTrials.gov; Identifier: NCT01644669. Findings Of the 878 participants treated, 877 participants received the prescribed 20 Gy dose with a mean radiation treatment time of 594.5 seconds, whereas one participant received 14 Gy due to a source failure. 569 participants have reached 18-month (333), 2-year (199), and 3-year (37) follow-up. The mean age at enrollment was 65 years (range 41-90). 219 participants had DCIS and 658 had invasive ductal carcinoma. The DCIS nuclear grade was high (N=79), intermediate (N=100), or low (N=40). Invasive cancers were Grade 1 (N=282), 2 (N=282), or 3 (N=94). 664 participants had T1 lesions, 56 had T2 lesions, and 3 were unknown. The mean tumor size was 12.33 ± 10.5 mm. Cosmesis was excellent to good in 90% of participants who reached 2-year follow-up. To date, 155 reported adverse events were Grade 2 or higher. The most frequent side effects were breast pain, seroma, induration, and erythema. There were nine deaths, none of which were breast cancer related, four ipsilateral breast recurrences, and three new contralateral breast cancers. Conclusions Early results from this multi-center trial demonstrate that IORT using the Xoft Axxent eBx System at the time of breast conservation surgery continues to be a promising treatment option for early stage breast cancer. The short course of radiation therapy for select patients has excellent to good cosmetic results and a low rate of high-grade adverse events and recurrences. Funding Funded by Xoft, Inc., a subsidiary of iCAD, Inc. Acknowledgement Medical writing support from Dr. Theresa E. Singleton, Singleton Science, LLC. Citation Format: Syed AMN, Chang H, Schwartzberg BS, Bremmer AK, Boylan S, Lopez-Penalver C, Vito CA, Davis M, Dooley WC, Chakravarthy AB, Croomer C, Proulx GM, Golder SL, Ivanov O, Fernandez KL, Farha M, Gonzalez V, Wengler C, Bhatnagar A, Neuner G, Kopkash K, Rahman S, Corn C, Costa P, Ellenhorn J, Cox C. Two-year follow-up results of a multi-center trial of intra-operative electronic brachytherapy during breast conservation surgery for early stage breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-19.

Abstract P1-10-20: A multi-center trial of intra-operative electronic brachytherapy during breast conservation surgery for early stage breast cancer: Early results of unplanned boost participants

Abstract Objective To assess the safety and efficacy of single-fraction, intra-operative radiation therapy (IORT) delivered as a boost using the Xoft® Axxent® Electronic Brachytherapy System® (eBx®) immediately following surgical resection for treatment of early stage breast cancer. Methods This phase 4, open-label, single-arm, prospective, non-randomized trial is still enrolling participants and is currently being conducted at 26 hospitals in the USA (25) and Portugal (1). 878 participants with biopsy-proven ductal carcinoma in situ (DCIS) or invasive ductal carcinoma who met the inclusion criteria underwent lumpectomy followed by single-fraction IORT to the lumpectomy cavity. Briefly, a small, presterilized lead shield piece was placed on the chest wall to reduce the dose to the ribs, and then a balloon applicator, suitable to the surgical bed, was placed in the lumpectomy cavity and inflated with saline (30-75 cc); skin was temporarily closed over the balloon and ultrasound was used to confirm a balloon surface-to-skin distance ≥ 1.0 cm. The Xoft System was used to deliver the 20 Gy dose at the balloon applicator surface. The balloon was deflated, lead shield and balloon removed and the surgical site sutured. Upon the presence of additional risk factors, 37 participants subsequently received whole breast radiation therapy (WBRT); thus, these participants received an unplanned IORT boost and were removed from the primary analysis but will continue to be followed for the duration of the 10-year study. Cosmesis (Harvard Scale) was assessed in this subset of participants. The primary outcome for the main trial is recurrence of ipsilateral breast tumor at 5 years. Trial Registry: ClinicalTrials.gov; Identifier: NCT01644669. Early Findings 37 boost participants received WBRT (up to 50 Gy) after IORT (36 received the prescribed 20 Gy dose; one received 14 Gy). Mean follow-up time was 430 days (range 13-1119). Mean age at IORT was 62 years (range 45-78). Boost participants had either DCIS (N=5) or invasive ductal carcinoma (N=32). The DCIS nuclear grade was high (N=3), intermediate (N=1), or low (N=1). Invasive cancers were Grade 1 (N=15), 2 (N=10), 3 (N=6), or unknown (N=1). 29 participants had T1, 3 had T2, and 5 had Tis lesions. Mean tumor size was 13.04 ± 10.26 mm. For the two participants who have reached 3-year follow-up, cosmesis was excellent (N=1) and fair (N=1). For the six participants who have reached 2-year follow-up, cosmesis was excellent (N=4), good (N=1), and fair (N=1). There was one serious adverse event with a Grade 3 for skin necrosis. The most frequent side effects were seroma (10%), edema (9%), pain (9%), erythema (6%), and induration (5%). There have been no deaths, recurrences, or new primary tumors among the boost participants to date. Conclusions Early results from this multi-center trial suggest that IORT as a tumor-bed boost using the Xoft Axxent eBx System at the time of breast conservation surgery is safe and has low morbidity. To date, the majority of participants receiving an unplanned IORT boost have had excellent to good cosmetic results and the majority of adverse events have been low-grade. Funding Funded by Xoft, Inc., a subsidiary of iCAD, Inc. Citation Format: Syed AMN, Chang H, Schwartzberg B, Bremner A, Boylan S, Lopez-Penalver C, Vito C, Davis M, Dooley W, Chakravarthy AB, Coomer C, Proulx G, Golder S, Ivanov O, Fernandez K, Farha MJ, Gonzalez V, Wengler C, Bhatnagar A, Neuner GA, Kopkash K, Rahman S, Costa P. A multi-center trial of intra-operative electronic brachytherapy during breast conservation surgery for early stage breast cancer: Early results of unplanned boost participants [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-20.

Early Results of a Multicenter Trial of Intraoperative Radiation Therapy Using Electronic Brachytherapy at the Time of Breast Conservation Surgery for Early-Stage Breast Cancer

Early Results of a Multicenter Trial of Intraoperative Radiation Therapy Using Electronic Brachytherapy at the Time of Breast Conservation Surgery for Early-Stage Breast Cancer