Initial Lumpectomy Research Articles

Abstract PO5-23-05: The Impact of Bi-Annual Diagnostic Imaging on Detecting Ipsilateral Breast Recurrence in Patients Undergoing Breast Conserving Surgery for Breast Cancer

Abstract Introduction: Breast conserving surgery (BCS) represents the preferred option for surgical treatment for a majority of patients with early-stage breast cancer who are eligible for this approach. When compared with mastectomy approaches, BCS provides patients with equivalent survival while preserving the affected breast. It is necessary to achieve clear surgical margins as positive lumpectomy margins are associated with an increased risk for ipsilateral breast tumor recurrence. With advances in imaging techniques, as well as effective systemic therapy and contemporary radiation therapy, local recurrence after BCS has decreased and overall survival for patients has improved. Retrospective studies have quantified the recurrence rate in unifocal breast cancer as 8 - 15% at 20 years. The NCCN recommends annual mammography at least 6 months after post-lumpectomy radiation therapy, but there is little data regarding more frequent surveillance after lumpectomy in the early post-operative setting. The purpose of this study was to evaluate the impact of short interval surveillance mammography on the detection of early in-breast recurrence in patients undergoing BCS. Methods: Our IRB-approved Breast Cancer Database was queried for patients enrolled from 11/2009 to 6/2023 who underwent breast conservation surgery for a diagnosis of in situ or invasive breast cancer in this retrospective analysis. Per our institutional protocol, patients were recommended to undergo diagnostic mammography of the treated breast(s) every 6 months for 2 years after BCS. After the initial 2 year period, bilateral mammography was performed annually in the absence of other indications. Additional supplemental imaging such as breast ultrasound and MRI were performed at physician discretion and based on patient risk and breast density. Variables of interest included the presence of pathogenic germline mutations, family history of breast cancer, and disease characteristics. Our primary endpoint was ipsilateral breast tumor recurrence. Results: Of 2491 patients who underwent breast conservation surgery for in situ or invasive breast cancer, 191 (7.7%) developed recurrent disease, including ipsilateral and contralateral recurrence, and distant disease, in the study period. A total of 83 (3.2%) patients developed ipsilateral breast recurrence during the entire study period. Of those, 19 (22.9%) were detected within the first two years after surgery. Six of the 19 patients (31.6%) had their recurrences detected on yearly diagnostic mammography while 6 (31.6%) patients had their recurrences detected on interval 6-month unilateral diagnostic imaging. In both groups, 5/6 recurrences were invasive disease after an original diagnosis of invasive cancer, and the remaining patient had recurrent DCIS. The remaining 7/19 patients (36.8%) had their ipsilateral recurrences detected on palpation or other diagnostic imaging. In this group as well, there was one case of recurrent DCIS, with the remaining 6 cases representing recurrent invasive cancer. Of the 19 patients with ipsilateral recurrences, none had pathogenic germline mutations. 4 of the 19 patients (21%) had positive margins after their initial lumpectomy surgery with re- excisions required to achieve clear margins. Conclusion: Interval diagnostic surveillance imaging every 6 months after breast conserving surgery identified almost one-third of the ipsilateral breast tumor recurrences that occurred within the first 2 years after surgery in our population. While our numbers are small, the relationship of re-excision lumpectomy surgery to subsequent risk for local recurrence has been described by others, and bears further study. Particularly in view of our observation that the majority of in-breast recurrences were invasive, our data supports the practice of more frequent imaging follow up in the first 2 years after breast conserving surgery. Citation Format: Pabel Miah, Laura Fiedler, Anthony Baez, Athanasios Sevdalis, Alyssa Marmer, Charles DiMaggio, Linda Pak, Richard Shapiro, Karen Hiotis, Deborah Axelrod, Amber Guth, Freya Schnabel. The Impact of Bi-Annual Diagnostic Imaging on Detecting Ipsilateral Breast Recurrence in Patients Undergoing Breast Conserving Surgery for Breast Cancer [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 PO5-23-05.

Does Nipple-Ward Positive Margin Contribute to a Higher Rate of Re-Excision Procedures After a Lumpectomy with Pathology-Confirmed Positive Margins? A Retrospective Study.

Positive margins on lumpectomy specimens are associated with a twofold increased risk of local breast tumor recurrence. Prior literature has demonstrated various techniques and modalities for assessing margin status to reduce re-excision rates. However, there is paucity of literature analyzing which margin contributes to the highest re-excision rates. Therefore, the primary aim of the study was to investigate whether the nipple-ward margins resulted in a higher rate of re-excision in our patient population. A retrospective chart review was performed on patients who had re-excision surgery. Nipple-ward margin was identified by correlating radiological and pathological reports. A cut-off of more than 25% was used to demonstrate correlation between nipple-ward margin and re-excision rate. A total of 98 patients' data were analyzed, with 41 (41.8%), 14 (14.3%), 5 (5.1%), and 38 (38.8%) diagnosed with DCIS, IDC, ILC, and mixed pathology on their margins, respectively. Overall, 48% (n=47) of the positive margins were nipple-ward, with 44.7% (n=21) reporting DCIS. Upon stratification, 45 (45.9%) cases were single-margin positive, with 26 (57.8%) being nipple-ward. Furthermore, the remaining 53 (54.1%) patients had multiple positive margins, with 21 (39.6.7%) nipple-ward cases. Positive nipple-ward margins significantly contribute to a higher re-excision rate p < 0.001; 48% of re-excision surgeries had positive nipple-ward margins, and 57.8% of positive single-margin cases were nipple-ward. Taking an additional shave during initial lumpectomy decreases re-excision rates. However, planning a lumpectomy procedure with a more elliptical rather than a spherical resection with additional cavity shave (ie, larger volume) in the nipple-ward direction and minimizing the remaining cavity shaves so the total volume resected remains unchanged. Nevertheless, future studies with larger sample sizes are required to bolster our findings.

EE67 Insurer and Patient Costs for Repeat Breast Surgery After Initial Lumpectomy for Breast Cancer

EE67 Insurer and Patient Costs for Repeat Breast Surgery After Initial Lumpectomy for Breast Cancer

Abstract OT2-07-01: Feasibility study to evaluate performance of the LUM Imaging System for intraoperative detection of residual tumor in breast cancer patients receiving and not receiving neoadjuvant therapy

Abstract Background: Microscopically tumor-free lumpectomy margins are critical for safe breast conserving surgery. With current tools, 15%-25% of lumpectomies have positive margins that require second surgical procedures and increase cost and patient discomfort. Additionally, current lumpectomy margin assessment techniques show poor performance in predicting residual disease at re-excision, with a PPV of 35%. Better detection tools are needed to identify residual cancer during the initial lumpectomy and reduce second operations. LUM015 is a protease-activated fluorescent imaging agent that accumulates in tumor cells and tumor associated macrophages after preoperative intravenous injection. The LUM Imaging System visualizes activated LUM015 in the lumpectomy cavity via a hand-held wide field detector and proprietary tumor detection software. This system has been tested in multiple single-site studies and two prospective multi-site studies enrolling &amp;gt;600 patients, and demonstrated successful detection of residual lumpectomy cavity tumor. Initial studies excluded the approximately 20% of patients receiving neoadjuvant therapy. Patchy tumor cell death with preoperative therapy can leave small, multifocal deposits of tumor invisible on pre-operative imaging and not palpable or visible during surgery. We now evaluate the LUM Imaging System in patients with and without neoadjuvant therapy. Trial Design and Specific Aims: This prospective, multi-center study at 6 US sites tests the LUM Imaging System in lumpectomy surgery after neoadjuvant therapy to evaluate potential impact of treatment-related tissue changes and tumor cell death on tumor detection algorithms. An initial cohort of 10 patients address the objective of algorithm development. A second cohort of 104 patients will further evaluate the feasibility of the LUM Imaging System after neoadjuvant therapy. A third cohort will enroll 208 patients who have not received neoadjuvant therapy. All cohorts are evaluated for safety and for reduction in residual tumor after LUM Imaging System guidance compared to standard of care lumpectomy. After excision of the main lumpectomy specimen, patients are randomized 3:1 to device or control arms. In the device arm, the cavity is imaged and margins with LUM015 signal are excised. Final comprehensive shaved margins are removed in both arms to evaluate extent of residual disease after the use of the LUM Imaging System or after standard lumpectomy. No LUM Imaging is performed in the control arm, however, all patients are injected with LUM015 to evaluate drug safety. Patient reported outcomes assessing re-excision concerns, breast appearance and preferences for treatment type are collected. Eligibility Criteria: This study seeks to enroll women 18 and older with histologically confirmed primary invasive breast cancer (IBC), ductal carcinoma in situ (DCIS) or a combination of IBC/DCIS undergoing a lumpectomy for their breast malignancy who have received any form of neoadjuvant treatment prior to surgery (cohorts 1 and 2) or who have not received any therapy prior to lumpectomy (cohort 3). Patients allergic to polyethylene glycol or intravenous contrast agents are excluded. Use of blue node mapping dyes before imaging with the LUM015 is not allowed per study protocol. Accrual and Study Progress: Cohort 1 has completed enrollment and interim analysis. No new risks specific to the neoadjuvant population were identified. LUM015 fluorescent signals measured in neoadjuvant patients were within the expected range, and no changes to the tumor detection algorithm were required. Cohorts 2 and 3 have enrolled a total of 38 patients. This trial is registered as NCT04440982. The NIH funds this study through a R01 grant issued to Massachusetts General Hospital. Citation Format: Irene L. Wapnir, Kelly K. Hunt, E Shelley Hwang, Kate Smith, Peter Blumencranz, David Carr, Jorge Ferrer, Heidi Santa Cruz, Alexandra Webster, Julia Shanno, Alexander Pogrebinsky, Manna Chang, Barbara L. Smith. Feasibility study to evaluate performance of the LUM Imaging System for intraoperative detection of residual tumor in breast cancer patients receiving and not receiving neoadjuvant therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-07-01.

Outcomes of Margin Reexcision after Oncoplastic Breast Reduction.

Introduction:Tissue rearrangement after an oncoplastic breast reduction may complicate identification of margins during reexcision. Little is known about outcomes of reoperation in this setting.Methods:This is a single-institution, retrospective analysis of outcomes of margin reexcisions after lumpectomy with concurrent oncoplastic Wise-pattern reduction from 2015 to 2020. Outcomes assessed were the rate of successful breast conservation, in-breast recurrence, wound issues or complications, effect on cosmesis, and delay to onset of adjuvant therapy.Results:From 2015 to 2020, 649 patients underwent lumpectomy with oncoplastic Wise-pattern reduction. Forty-seven patients (7.2%) had greater than or equal to one positive margin(s); of these, 28 went directly to mastectomy, and 19 underwent margin reexcision. Residual disease was found in seven of 19 patients (37%) at reexcision. The rate of successful breast-conserving therapy was 95% with a mean follow-up of 31 months. There was one (5%) in-breast recurrence (invasive ductal carcinoma [IDC] occurring 30 months after the original operation); this patient had a mastectomy for treatment of her recurrence. The overall complication rate was 37%. Radiation was administered to 18 patients (95%), and two patients (11%) had delay of radiation past 6 weeks due to wound complications. Of the 14 patients with photographs available, 12 of 14 patients (86%) were blindly assessed to have equivalent or better cosmesis after margin reexcision (versus initial lumpectomy).Conclusion:Margin reexcision after oncoplastic breast reduction with Wise-pattern is feasible and effective, and can be done without compromising the initial cosmetic results.

Targeted Intraoperative Radiotherapy (TARGIT-IORT) for Early-Stage Invasive Breast Cancer: A Single Institution Experience.

Purpose/ObjectiveWe present our single-institution experience in the management of invasive breast cancer with targeted intraoperative radiotherapy (TARGIT-IORT), focusing on patient suitability for IORT determined by the American Society for Radiation Oncology (ASTRO) Accelerated Partial Breast Irradiation (APBI) consensus guidelines.Materials/MethodsWe identified 237 patients treated for biopsy-proven early-stage invasive breast cancer using low energy x-ray TARGIT-IORT at the time of lumpectomy between September 2013 and April 2020 who were prospectively enrolled in an institutional review board (IRB) approved database. We retrospectively reviewed preoperative and postoperative clinicopathologic factors to determine each patient’s ASTRO APBI suitability (suitable, cautionary or unsuitable) according to the 2017 consensus guidelines (CG). Change in suitability group was determined based on final pathology. Kaplan-Meier methods were used to estimate the survival probability and recurrence probability across time.Results237 patients were included in this analysis, based on preoperative clinicopathologic characteristics, 191 (80.6%) patients were suitable, 46 (19.4%) were cautionary and none were deemed unsuitable. Suitability classification changed in 95 (40%) patients based on final pathology from lumpectomy. Increasing preoperative lesion size or a body mass index (BMI) ≥ 30 kg/m2 were significant predictors for suitability group change. Forty-one (17.3%) patients received additional adjuvant whole breast radiotherapy after TARGIT-IORT. At a median follow up of 38.2 months (range 0.4 – 74.5), five (2.1%) patients had ipsilateral breast tumor recurrences (IBTR), including two (0.8%) true local recurrences defined as a recurrence in the same quadrant as the initial lumpectomy bed with the same histology as the initial tumor. IBTR occurred in 1/103 (0.09%) patient in the post-op suitable group, 4/98 (4.08%) patients in the post-op cautionary group, and no patients in the post-op unsuitable group. At 3-years, the overall survival rate was 98.4% and the local recurrence free survival rate was 97.1%.ConclusionThere is a low rate of IBTR after TARGIT-IORT when used in appropriately selected patients. Change in suitability classification pre to postoperatively is common, highlighting a need for further investigation to optimize preoperative patient risk stratification in this setting. Patients who become cautionary or unsuitable based on final pathology should be considered for additional adjuvant therapy.

Abstract P3-18-12: Achieving negative margin after repeated attempts for lumpectomy does not nullify the risk of ipsilateral breast tumor recurrences

Abstract Introduction: Currently, the widely accepted principle in managing lumpectomy margins in early breast cancer patients is to avoid the presence of tumor cell at the margin. The presence of tumor cells on lumpectomy margin can represent two different aspects of local control in breast cancer. One aspect is related to the potential technical failure that may lead to an incomplete resection of the tumor. The other aspect of positive margin is associated with a biologic nature of the tumor. For example, some tumors show features of extensive intraductal component which often result in positive lumpectomy margins and may lead to increased risk of local recurrence after breast conservation surgery. Therefore, the two-fold increase of IBTR risk with positive margin would be the reflection of the combined effect of both technical failure and the biologic features.In this study, we aimed to address this issue by investigating the IBTR rates of patients in whom negative margins were achieved by initial lumpectomy or by re-excision. Our assumption was if the IBTR rates of the two groups are identical, then the two-fold increase of IBTR risk is mostly caused by the technical incomplete resection and therefore the measures to achieve negative margins would be justified. Methods: We retrospectively reviewed the data of 5,633 patients who underwent breast conservation surgery and whole breast irradiation for invasive breast cancer between January 2004 and December 2018 from Seoul National University Hospital. During the period, a total of 828 patients had positive lumpectomy margin after their initial surgery. Among them, thirty-five patients who did not undergo re-operation were excluded due to the small sample size. Results: The median age of the studied patients was 49 years old (19-92), and nearly two third of the patients had T1 tumors (64.3%). 4,293 patients (76.7%) were node negative and 4,332 patients (77.4%) had hormone receptor positive tumors. During the median follow-up period of 76.6 ( ± 44.6) months, a total of 121 patients (2.2%) experienced IBTR. Patients who underwent re-excision to achieve negative margins experienced significantly higher rate of IBTR compared to patients in whom the margins were clear at the first lumpectomy (p=0.031, HR: 1.61; 95% C.I., 1.04-2.48). The survival curves began to separate around 4-5 years after surgery (98.5% vs 98.0% at 5 year and 97.4% vs 94.7% at 10 years of follow-up). The survival difference was more clearly observed for younger patients (p=0.033, HR 1.72; 95% C.I., 1.04-2.85 for age less than 50). When the patients were divided according to their hormone receptor and HER2 amplification status, we observed significant difference in HR+/HER2- and HR-/HER2- subtypes while the HER2-amplified tumors showed no significant differences.By using Cox regression analysis, we adjusted for other significant predictors of IBTR such as age, histologic grade, lymphovascular invasion, hormone receptor status, HER2 amplification status, and Ki-67 levels. The results of the Cox regression analysis showed that re-excision to achieve negative margin is significantly associated with the risk of IBTR after adjusting for these variables (p=0.023, HR: 1.72; 95% C.I., 1.08-2.74). Conclusion: Patients who underwent re-excision after lumpectomy for initial positive margin carry increased risk of developing IBTR even they achieve final negative margin when compared to patients with initially negative lumpectomy margin. Our observation indicate that a substantial proportion of the increasing risk of IBTR associated with positive lumpectomy margin can be attributed to the biologic characteristics of the tumor rather than technical incomplete resection. Citation Format: Jong Ho Cheun, Hong-Kyu Kim, Han-Byoel Lee, Wonshik Han, Hyeong-Gon Moon. Achieving negative margin after repeated attempts for lumpectomy does not nullify the risk of ipsilateral breast tumor recurrences [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 P3-18-12.

Abstract OT2-12-02: Feasibility study to evaluate performance of the LUM imaging system for intraoperative detection of residual tumor in patients with breast cancer receiving neoadjuvant therapy

Abstract Background: Microscopically tumor-free lumpectomy margins are the goal for breast conserving surgery. With current tools, 15% to 25% of lumpectomies have positive margins and require a second surgical procedure increasing cost and patient discomfort. In addition, current lumpectomy margin assessment techniques show poor performance in predicting residual disease at re-excision, with a PPV of only 35%. Better detection tools are needed to guide the removal of cancer missed during the initial lumpectomy and reduce second operations. The LUM015 imaging agent is injected intravenously before surgery and its fluorescence signal is activated by proteases in tumor cells and the invasive front. The LUM Imaging System visualizes the activated LUM015 in the lumpectomy cavity via a hand-held detector and proprietary tumor detection software. This system was previously tested in multiple single-site studies and a prospective 234 patient multi-site study that demonstrated successful detection of residual cancer in the lumpectomy cavity. Initial studies excluded the ~20% of breast cancer patients receiving neoadjuvant therapy. Patchy tumor cell death with preoperative therapy can leave small, multifocal deposits of tumor invisible on pre-operative imaging and not palpable or visible during surgery. In this study, we are evaluating the LUM Imaging System in this patient population. Trial Design and Specific Aims: A prospective, multi-center study was designed to evaluate the potential impact of neoadjuvant therapy on tumor detection algorithms, which will be refined if needed. The first cohort of 10 patients will address this objective. A second cohort will further evaluate the feasibility, safety and efficacy of the LUM Imaging System in this patient population. 114 neoadjuvant therapy patients with invasive breast cancer and/or ductal carcinoma in situ will enroll at 6 US medical centers. After excision of the main lumpectomy specimen, patients are randomized 3:1 to device or control arms. In the device arm, the cavity is imaged and margins with LUM015 positive signal are excised. In the control arm, the surgeon records images within the cavity but no LUM015-directed margins are excised. Final comprehensive shave margins are removed in both arms to evaluate extent of residual disease after the use of the LUM Imaging System or after standard lumpectomy resection. Eligibility Criteria: This study seeks to enroll women, over the age of 18 and primary invasive breast cancer (IBC), ductal carcinoma in situ (DCIS) or a combination of IBC/DCIS undergoing a lumpectomy for their breast malignancy who have received any form of neoadjuvant treatment prior to undergoing surgery. Exclusions include patients allergic to polyethylene glycol or contrast agents. Use of blue node mapping dyes before imaging with the LUM015 is not allowed. Accrual and Study Progress: Cohort 1 has completed enrollment and interim analysis. No new risks specific to this patient population were identified and the fluorescence signals measured were within the expected range resulting in no initial changes to the tumor detection algorithm. Four patients have enrolled into cohort 2. This trial is registered as NCT04440982. This study is funded by NIH grant R01CA212138 awarded to Dr. Barbara Smith. Citation Format: Kate P Smith, Jorge Ferrer, Alexandra Webster, Bridget Kelly, Brian Schlossberg, Manna Chang, Barbara Smith. Feasibility study to evaluate performance of the LUM imaging system for intraoperative detection of residual tumor in patients with breast cancer receiving neoadjuvant therapy [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 OT2-12-02.

Abstract OT2-12-03: Pivotal study of the Lum imaging system for assisting intraoperative detection of residual cancer in the tumor bed of female patients with breast cancer: The INCITE trial

Abstract Background Breast-conserving surgery is a critical step in treatment with the goal of removing all cancer cells while minimizing the removal of healthy tissue. 15% to 25% of lumpectomy patients have positive margins and require a second surgery to achieve negative margins and reduce the risk of local recurrences. These positive margins are poorly predictive (35% PPV) of cancer left in the cavity, so most second surgeries find no residual cancer. Better detection tools are needed to guide in real-time the removal of cancer missed during the initial lumpectomy to reduce the number of second operations. The pegulicianine imaging agent is injected intravenously before surgery and its fluorescence signal is activated by proteases in tumor cells and cells at the tumor margin. The LUM Imaging System visualizes activated pegulicianine in the lumpectomy cavity via a hand-held detector and proprietary tumor detection software. This system was previously tested in multiple single-site studies and a prospective multi-site study that enrolled 234 patients and showed good ability to detect residual cancer in the lumpectomy cavity. Trial Design and Specific Aims: The current prospective, multi-center, randomized, blinded study was designed to show the clinical efficacy, system accuracy, and safety of the LUM Imaging System. It aims to demonstrate guided removal of residual cancer in the lumpectomy missed during the initial procedure and potentially reduce the rates of positive margins. This study is powered by an event-driven design that requires 70 truth-standard positive events. It is expected that approximately 390 women at fourteen medical centers across the US will be enrolled to achieve the number of events. Pegulicianine is injected 2-6 hours prior to the lumpectomy procedure. Surgeons perform standard of care (SOC) lumpectomy followed by blinded intraoperative imaging of the lumpectomy cavity with the LUM Imaging System in regions where SOC shaves will be taken. The patient is then randomized. If the random assignment is to the device arm, the surgeon is directed to excise margins that have positive LUM signal. Pathologists are blinded to the source of tissue removed (SOC vs. LUM) when conducting the pathology assessment. The amount of additional tissue volume resected is also evaluated. Patient reported outcome data is collected as a quality-of-life survey before and after the subject’s lumpectomy.Eligibility Criteria: This study seeks to enroll women with primary invasive breast cancer (IBC), ductal carcinoma in situ (DCIS) or a combination of IBC/DCIS undergoing a lumpectomy for their breast malignancy. Patients must not have a history of allergic reaction to polyethylene glycol, contrast agents, or have received neoadjuvant therapy to treat their current breast cancer. Use of blue dyes before imaging with the LUM System are not allowed. Additional detailed eligibility criteria are listed in the protocol. Accrual and Study Progress To date, 350 subjects have participated in this trial. This study is funded in part by the National Cancer Institute (5R44CA211013). This trial is registered as NCT03686215. Citation Format: Jorge Ferrer, David Carr, Peter Blumencranz, Irene Wapnir, Donna Dyess, Shelly Hwang, Nayana Dekhne, Daleela Dodge, Beth-Ann Lesnikoski, Kelly Hunt, Patricia Clark, Stephanie Valente, Marie Catherine Lee, Lynne Clark, Brian Schlossberg, Sean Madden, Alejandra Rodriguez, Kate Smith, Manna Chang, Barbara Smith. Pivotal study of the Lum imaging system for assisting intraoperative detection of residual cancer in the tumor bed of female patients with breast cancer: The INCITE 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 OT2-12-03.

Maintaining Contour with a Three-dimensional Interstitial Tissue Marker in 134 Lumpectomies.

Background:Breast-conserving surgery (BCS) is meant to preserve the natural appearance of the breast; however, tissue volume deficits cannot always be compensated by soft tissue mobilization. A three-dimensional (3D) interstitial tissue marker (BioZorb) was designed to delineate the lumpectomy cavity for targeting boost irradiation, but an unexpected secondary benefit may be in guiding wound contraction and restoring contour to the lumpectomy bed. We analyze tissue volume excised at the time of lumpectomy as a function of device size selected.Methods:In total, 134 consecutive lumpectomy patients implanted with BioZorb between May 2015 and February 2020 were retrospectively analyzed for tissue volume excised, device size used, location, and re-operation rates, including explantation of the device.Results:An estimated 113 patients underwent device implantation at initial lumpectomy, and 21 at margin re-excision. Twenty-seven patients underwent re-excision, while 14 elected mastectomy for positive margins following insertion; 22 had the same device reimplanted. Mean lumpectomy volume was 79.0 cm3 (range 10.3–275.8 cm3) during the first implant procedure. Large-volume lumpectomies, averaging 136.5 cm3, were associated with selection of larger devices, which aided in restoring volume and maintaining breast contour. Three (2.2%) patients requested removal of the device.Conclusions:BioZorb implantation can be a safe and useful oncoplastic technique for restoring volume with BCS. Large-volume lumpectomies can be performed without contouring defects using the device. An unexpected secondary benefit of the device may be scaffolding for wound contraction.

Abstract CT245: Feasibility study to evaluate performance of the Lum Imaging System for intraoperative detection of residual tumor in patients with breast cancer receiving neoadjuvant therapy

Abstract Background: Microscopically tumor-free lumpectomy margins are critical for safe breast conserving surgery. With current tools, 15% to 25% of lumpectomies have positive margins and require a second surgical procedure increasing cost and patient discomfort. In addition, current lumpectomy margin assessment techniques show poor performance in predicting residual disease at re-excision, with a PPV of 35%. Better detection tools are needed to identify residual cancer during the initial lumpectomy and reduce second operations. LUM015 is a protease-activated fluorescent imaging agent that accumulates in tumor cells and tumor associated macrophages injected intravenously before surgery. The LUM Imaging System visualizes the activated LUM015 in the lumpectomy cavity via a hand-held wide field detector and proprietary tumor detection software. This system was previously tested in multiple single-site studies and a large, prospective 234 patient multi-site study that demonstrated successful detection of residual lumpectomy cavity. Initial studies excluded the approximately 20% of breast cancer patients receiving neoadjuvant therapy. Patchy tumor cell death with preoperative therapy can leave small, multifocal deposits of tumor in visible on pre-operative imaging and not palpable or visible during surgery. In this study, we evaluated the LUM Imaging System in this patient population. Trial Design: A prospective, multi-center study was designed to test feasibility of the LUM Imaging System in lumpectomy surgery after neoadjuvant therapy. This will evaluate potential impact of microenvironment changes after treatment and tumor cell death on tumor detection algorithms. Algorithms will be refined if needed. 10 patients will address this objective. A second cohort will further evaluate the feasibility, safety and efficacy of the LUM Imaging System in this patient population. 114 patients with invasive breast cancer and/or ductal carcinoma in situ will enroll at 5 US medical centers. Exclusions include patients allergic to polyethylene glycol or intravenous contrast agents. Use of blue node mapping dyes before imaging with the LUM015 is not allowed. After excision of the main lumpectomy specimen, patients are randomized 1:3 to device or control arms. In the device arm, the cavity is imaged and margins with LUM015 signal are excised. In the control arm, the surgeon records images within the cavity but no LUM015-directed margins are excised. Final comprehensive shave margins are removed in both arms to evaluate extent of residual disease after the use of the LUM Imaging System or after standard lumpectomy resection. Cohort 1 has completed enrollment. No patients have enrolled into cohort 2. This trial is registered as NCT04440982. This study is funded by the NIH through a R01 research grant issued to Massachusetts General Hospital. Citation Format: Jorge Ferrer, Bridget Kelly, Alexandra Webster, Brian Schlossberg, Kate Smith, Manna Chang, Barbara Smith. Feasibility study to evaluate performance of the Lum Imaging System for intraoperative detection of residual tumor in patients with breast cancer receiving neoadjuvant therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT245.

Abstract CT259: Pivotal Study of the LUM Imaging System for assisting intraoperative detection of residual cancer in the tumor bed of female patients with breast cancer

Abstract Background Breast-conserving surgery is a critical first step in treatment with the goal of removing all cancer cells while minimizing the removal of healthy tissue. 15% to 25% or more of lumpectomy patients have positive margins and require a second surgery to achieve negative margins and reduce the risk of local recurrences. These positive margins are poorly predictive (35% PPV) of cancer left in the cavity, so most second surgeries find no residual cancer. Better detection tools are needed to identify residual cancer in real time during the initial lumpectomy to reduce the number of second operations. LUM015 is a protease-activated fluorescent imaging agent that accumulates in tumor cells and tumor associated macrophages. The LUM Imaging System camera visualizes the intravenously injected LUM015 in the lumpectomy cavity via a hand-held wide field detector and proprietary tumor detection software. This imaging system was previously tested in multiple single-site studies and a large, prospective multi-site study that enrolled 234 patients and showed good ability to detect residual cancer in the lumpectomy cavity. Trial Design The current prospective, multi-center, randomized, blinded study was designed to demonstrate the clinical efficacy, system accuracy, and safety of the LUM Imaging System. It aims to identify residual cancer in the lumpectomy cavity to reduce the rates of positive margins. This study seeks to enroll women with primary invasive breast cancer (IBC), ductal carcinoma in situ (DCIS) or a combination of IBC/DCIS undergoing a lumpectomy for their breast malignancy. Approximately 310 women at 14 US medical centers will be enrolled. This study is powered by an event-driven design that requires 70 patients to be enrolled that have a ‘truth-standard positive' event, which is the identification of cancer in a protocol defined tissue type. To be eligible, patients must not have a history of allergic reaction to polyethylene glycol, intravenous contrast agents, or systemic therapies to treat their cancer. Use of blue dyes before imaging with the LUM System are not allowed. LUM015 is injected prior to the lumpectomy procedure. Surgeons perform standard of care (SOC) lumpectomy and perform blinded intraoperative imaging of the lumpectomy cavity with the LUM Imaging System in regions where SOC shaves will be taken. The patient is then randomized. If the random assignment is to the device arm, the surgeon is directed to excise margins that the LUM System indicates are positive for cancer. Pathologists are blinded to the type of tissue removed when conducting the pathology assessment. Patient reported outcome data is collected as a quality-of-life survey before and after the subject's lumpectomy. Additional detailed eligibility criteria are in the protocol. To date, 166 patients have participated in this trial. This trial is registered as NCT03686215. Citation Format: Jorge Ferrer, David Carr, Peter Blumencranz, Irene Wapnir, Donna Dyess, Shelly Hwang, Nayana Dekhne, Daleela Dodge, Beth-Ann Lesnikoski, Kelly Hunt, Patricia Clark, Stephanie Valente, M. Catherine Lee, Lynne Clark, Brian Schlossberg, Sean Madden, Alejandra Rodriguez, Kate Smith, Manna Chang, Barbara Smith. Pivotal Study of the LUM Imaging System for assisting intraoperative detection of residual cancer in the tumor bed of female patients with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT259.

Prognostic factors for residual occult disease in shave margins during partial mastectomy.

Shave margins have been shown to decrease positive final margins in partial mastectomy. We investigated prognostic factors associated with residual disease in shave margins. Patients with invasive breast carcinoma and ductal carcinoma in situ (DCIS) who had circumferential shave margins excised during lumpectomy were abstracted from a retrospective database from 2015 to 2018. We defined residual occult disease (ROD) as either (1) residual disease in a shave margin when the initial lumpectomy specimen had negative margins or (2) residual disease in a shave margin that did not correspond with the positive lumpectomy margin. We identified the frequency of ROD and conducted logistic regression analysis to identify associated prognostic factors. 166 Patients (139 invasive carcinoma, 27 DCIS) were included with median follow-up of 28months (9-50months). Residual occult disease existed in 34 (24.5%) with invasive carcinoma and 8 (29.6%) with DCIS. In univariate analyses of the invasive group, invasive lobular carcinoma and a positive initial, non-corresponding lumpectomy margin were predictive of ROD (OR 3.63, p = 0.04, OR 3.48, p = 0.003 respectively). In multivariate analysis, a positive lumpectomy margin remained significant, p = 0.007. No variables were associated with ROD in DCIS. Residual occult disease was shown to be a frequent event in this analysis of lumpectomy with circumferential shave margins. Having a positive initial lumpectomy margin was predictive of ROD in a non-corresponding margin. Surgeons should consider not being selective in their shave margins or margin of re-excision if shave margins were not obtained in their initial surgery.

Abstract PS15-19: Preoperative selection of patients with early-stage invasive breast cancer for intraoperative radiation therapy (IORT): A single-institution experience

Abstract Purpose/Objective: Intraoperative radiation therapy (IORT) is a form of accelerated partial breast irradiation (APBI) delivered at the time of lumpectomy for early-stage breast cancer. Upfront selection of patients based on favorable preoperative characteristics is important to achieve good outcomes. Here we present our single-institution experience in the management of invasive breast cancer with IORT. We focused on the classification of patient suitability for IORT by the American Society for Therapeutic Radiation Oncology (ASTRO) APBI consensus guidelines using preoperative and postoperative clinicopathologic factors, as well as treatment outcomes and recurrences. Materials/Methods: We reviewed our institutional prospective registry database (AAAJ8512) to identify patients with biopsy-proven invasive breast cancer treated with breast IORT between 9/2013 and 4/2020 using the Zeiss Intrabeam™. Patients received a single dose of 20Gy delivered to the lumpectomy cavity surface at the time of planned surgery. We excluded patients from analysis with prior radiation to the breast, or triple negative disease at initial diagnosis. We reviewed preoperative and postoperative clinicopathologic factors to determine each patient’s ASTRO APBI suitability (suitable, cautionary or unsuitable) based on the 2017 consensus guidelines. Results: 237 patients were treated with IORT for early stage breast cancer. Median age was 67 years (range 44-94 years). Median extent of disease by conventional imaging was 1.0 cm (range 0 - 3.0cm). 51/103 (49.5%) patients with heterogeneously or extremely dense breasts underwent a MRI preoperatively. Based on preoperative clinicopathologic characteristics, 191 (80.6%) patients were suitable according ASTRO APBI guidelines, 46 (19.4%) cautionary and no patients were unsuitable. APBI group suitability changed in 95 (40.1%) patients based on final pathology from the time of lumpectomy, summarized in Table 1. 17 (7.2%) patients underwent re-excision for close or positive margins. 39 (16.5%) patients received additional adjuvant whole breast radiotherapy including 10/18 (56%) of unsuitable patients. Of 212 (89.5%) patients who initiated hormone therapy (HT), 191 (80.6%) were compliant at last follow up. Median follow-up for all patients was 38.2 months (0.4 - 74.5). Five (2.1%) patients experienced ipsilateral breast tumor recurrence, 1 (0.4%) patient experienced new contralateral breast cancer, and 2 (1.6%) patients experienced distant recurrence with the median time to event of 27.8 months (range 6.3-50.4). Of the 5 patients with ipsilateral breast tumor recurrence, 2 (0.8%) were true local recurrences &amp;lt;2cm from the initial lumpectomy bed with the same histology as initial tumor, both cases were cautionary risk and one declined HT, 3 (1.3%) were new breast primaries occurring &amp;gt;2cm from lumpectomy bed with a different histology. Conclusion: Breast IORT is an attractive cost-effective option for women with early stage breast cancer, and our 3-year true local recurrence rate is 0.8%. Optimal patient selection is key based on preoperative characteristics. Patients who become unsuitable or cautionary for APBI based on final pathology should be considered for additional adjuvant therapy. Table 1ReasonASTRO APBI Pre-Op Suitability#SizeER (-)AgeT2ILCSuitable191Cautionary46114101122Unsuitable0ASTRO APBI Post-Op Suitability Change#SizeClose MarginsPositive MarginsLVIMultifocalILCEICSuitable to Cautionary7792023211124Suitable to Unsuitable12111Cautionary to Unsuitable624Abbreviations: ER = Estrogen Receptor; ILC = Invasive Lobular Carcinoma; LVI = Lymphovascular Invasion; EIC = Extensive Intraductal Component Citation Format: Andrea M Brown, Christine Chin, Eileen Connolly, Roshni Rao, Bret Taback, Lisa Wiechmann. Preoperative selection of patients with early-stage invasive breast cancer for intraoperative radiation therapy (IORT): A single-institution experience [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 PS15-19.

Abstract CT281: Pivotal study of the LUM Imaging System for assisting intraoperative detection of residual cancer in the tumor bed of female patients with breast cancer

Abstract Background: For many women with breast cancer, breast-conserving surgery is a critical first step in treatment with the goal of removing all cancer cells while minimizing the removal of healthy tissue. 15% to 25% or more of lumpectomy patients have positive margins and require a second surgery to achieve negative margins and reduce the risk of local recurrences. These positive margins are poorly predictive (35% PPV) of cancer left in the cavity, so most second surgeries find no residual cancer. Better detection tools are needed to identify residual cancer in real time during the initial lumpectomy to reduce the number of second operations. LUM015 is a protease-activated fluorescent imaging agent that accumulates in tumor cells and tumor associated macrophages. The LUM Imaging System camera visualizes the intravenously injected LUM015 in the lumpectomy cavity via a hand-held wide field detector and proprietary tumor detection software. This imaging system was previously tested in multiple single-site studies and a large, prospective multi-site study that enrolled 234 patients and showed good ability to detect residual cancer in the lumpectomy cavity. Trial Design: The current prospective multi-center, two-arm randomized, blinded study was designed to demonstrate the clinical efficacy, system accuracy, and safety of the LUM Imaging System. It aims to identify residual cancer in the lumpectomy cavity in order to reduce the rates of positive margins. This study seeks to enroll women with confirmed primary invasive breast cancer (IBC), ductal carcinoma in situ (DCIS) or a combination of IBC/DCIS undergoing a lumpectomy for their breast malignancy. The planned enrollment is 170 women being treated at fifteen medical centers across the US. To be eligible, patients must not have a history of allergic reaction to polyethylene glycol, intravenous contrast agents, or systemic therapies to treat their cancer. Use of blue dyes before imaging with the LUM System are not allowed. LUM015 is injected prior to the lumpectomy procedure. Surgeons perform standard of care (SOC) lumpectomy and perform blinded intraoperative imaging of the lumpectomy cavity with the LUM Imaging System in any regions where SOC shaves will be taken. The patient is then randomized either the further use of device or not. If the random assignment is to the device arm, the surgeon is directed to excise margins that the LUM System indicates are positive for cancer. Pathologists are blinded to the type of tissue removed when conducting the pathology assessment. Patient reported outcome data is collected as a quality of life survey before and after the subject's surgery. Additional detailed eligibility criteria are listed in the protocol. To date, 22 subjects have participated in this trial. This trial is registered as NCT03686215. Citation Format: Jorge Ferrer, David Carr, Irene Wapnir, Kelly Hunt, Peter Blumencranz, Nayana Dekhne, Daleela Dodge, Donna Lynn Dyess, Shelley Hwang, Stephanie Valente, Lynne Clark, Beth-Ann Lesnikoski, Anees Chagpar, Paticia Clark, Marie Catherine Lee, Brian Schlossberg, Sean Madden, Livia Gjylameti, Manna Chang, Kate Smith, Barbara Smith. Pivotal study of the LUM Imaging System for assisting intraoperative detection of residual cancer in the tumor bed of female patients with breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT281.

A Single institution's randomized double-armed prospective study of lumpectomy margins with adjunctive use of the MarginProbe in nonpalpable breast cancers.

Breast conservation surgery (BCS) aims to excise all cancerous tissue while minimizing the amount of healthy breast tissue removed. Up to 30% of patients undergoing BCS require a second operation for re-excision to obtain negative margins. Previous studies reported a lower re-excision rate with intraoperative use of the MarginProbe device (Dune Medical Devices). This device utilizes radiofrequency spectroscopy to detect differences between cancerous and normal tissue. From July 2009 to January 2010, our institution enrolled 46 patients electing for BCS in a prospective double-arm randomized controlled trial and had a significantly lower re-excision rate than that reported in the multicenter trial. Intraoperatively, after performing conventional lumpectomy with excision of any additional shavings deemed necessary based on palpation and visual inspection alone, patients were then randomized. In the device arm, the surgeon used the MarginProbe to interrogate the lumpectomy specimen, taking additional shavings from the cavity surfaces corresponding to the parts of the specimen read as positive by the device. In the control arm, only standard intraoperative assessments were performed. All specimens were evaluated by pathologists who were blinded to the study arm. In this population, 72% had invasive ductal carcinoma (IDC), 20% had ductal carcinoma in situ (DCIS), and 8% had invasive lobular carcinoma (ILC). Average age was 64years old. The average size of the specimen was 5.6cm, the average volume was 37.8cm3 , and the average weight was 32.7g. The mean size of DCIS was 1.4cm. For invasive specimens, 32 were T1 and 7 were T2. Prior to randomization, 43 patients were thought to have positive or close margins and therefore underwent additional shavings. Twenty-three patients were randomized to the device arm and 23 to the control arm. In the device arm, 14 (60%) patients had IDC, 7 (30%) had DCIS, and 2 (8%) had ILC, vs the control arm where 19 (82%) patients had IDC, 2 (8%) had DCIS, and 2 (8%) had ILC. Eight (35%) patients in the control group vs 1 (4%) in the device group underwent re-excision for margin involvement (P<.05). The use of the MarginProbe device at our institution significantly improved the ability of our surgeons to obtain clear margins during initial BCS. Our results show a lower re-excision rate (4%) than those published in the multicenter trial (19.8%). We postulate that in the face of more patients having DCIS in our device group (30%), our surgeons responded by taking thicker shavings when the MarginProbe device reported margin involvement during the initial lumpectomy, resulting in greater success achieving clear final margins on the shaved tissue and a significantly lower re-excision rate than previously reported with the MarginProbe device.

Utility of Taking Additional Margins When Performing Breast-Conserving Surgery with Intraoperative Radiation Therapy for Early Breast Cancer.

Intraoperative radiation therapy (IORT) is an alternative to external beam radiation therapy (EBRT) after lumpectomy, in which radiation is delivered before the final margin analysis. Practices vary regarding excision of close or positive margins pre- and post-IORT. In a retrospective cohort of women with hormone receptor-positive, clinically node-negative breast cancer undergoing lumpectomy with IORT and selective EBRT at our institution from 2011 to 2015, we compared the impact of pre- and post-IORT margin excisions on in-breast tumor recurrence. Additional pre-IORT margins were taken at surgical team discretion. Re-excisions post-IORT were performed for positive/close margins. We describe rate of invasive or in situ malignancy in additional pre-IORT and post-IORT re-excised specimens and compare IBTR using Chi-squared tests. There were 195 cases in 193 women (2 bilateral breast cancer). Pre-IORT, ≥1 additional margin was obtained in 139 (71%). The final margin on the initial lumpectomy was positive in 13 (9%) and ≤2mm in 72 (52%). Additional pre-IORT margins contained in situ/invasive cancer in 16 (12%). Thirty-one patients (16%) underwent post-IORT re-excision and nine (29%) contained invasive/in situ malignancy. Twenty-three (12%) received EBRT. In 45.6-month mean follow-up, 13 had IBTR (7%) with no difference by additional pre-IORT margin excision (5 vs. 11%, p = 0.150), post-IORT margin re-excision (10 vs. 6%, p = 0.464), or EBRT (0 vs. 8%, p = 0.172). Adjuvant endocrine therapy was associated with lower IBTR (4 vs. 17%, p = 0.003). Taking additional pre-IORT margins and re-excising close/positive margins post-IORT improved margin clearance rates but had an unclear effect on IBTR. Adjuvant endocrine therapy significantly reduced IBTR.

Abstract P3-09-17: Preoperative pembrolizumab increases sTILs in treatment naïve stage I/IIA TNBC patients in a window of opportunity trial

Abstract Background: High levels of stromal tumor-infiltrating lymphocytes (sTILs) are significantly associated with chemosensitivity and improved overall survival for patients with triple negative breast cancer (TNBC). Our aim is to determine if we can significantly increase sTILs from biopsy to lumpectomy in a presurgical window of opportunity trial with pembrolizumab and intraoperaperative radiation (IORT) in treatment-naïve early stage TNBC compared to matched IORT only controls. We also evaluate the changes in the spatial distribution of intraepithelial TILs (iTILs) by utilizing a deep learning algorithm. Our secondary aim is to characterize the tumor immune microenvironment (TME) using quantitative multiplex immunofluorescence (qmIF) and transcriptomic analysis of tumor-associated and immune genes. Methods: Seven women with node negative TNBC &amp;lt;2.5 cm were enrolled in either our presurgical trial with pembrolizumab and IORT as an upfront boost (NCT02977468) or a parallel study with IORT alone (NCT03165487). The treatment consisted of two doses of pre-operative pembrolizumab (200mg IV) given alone with the second dose -10 to -18 days from surgery; 20Gy IORT was delivered during surgery to the lumpectomy bed. All patients completed standard of care adjuvant chemotherapy and whole breast irradiation. Initial analyses performed include assessments of sTILs and iTILs on H&amp;E sections from the initial biopsy and lumpectomy. iTILs were identified with a deep learning algorithm in pathologist annotated regions with invasive carcinoma, excluding in situ legions. Deep learning derived percentages of iTILs were validated through comparison with manual estimates performed by a pathologist per international guidelines. Spatial clustering analysis with iTILs was performed by calculating the Ball-Hall index for each case to measure the mean dispersion through all the clusters. Results: Seven patients were enrolled between Nov 2017-Apr 2019; 3 patients received pembrolizumab+IORT; and 4 patients received IORT alone. Initial pathology assessment of sTILs demonstrated no significant change between biopsy and lumpectomy in control patients. No consistent patterns of iTILs dispersion were observed in the control patients. Out of the 3 pembrolizumab treated patients, one patient demonstrated a marked increase in sTILs (20% to 60%) with a shift from a neutrophil rich to lymphoplasmacytic stromal infiltrate where the mean dispersion of the iTILs doubled (180 to 360). In the other 2 pembrolizumab patients, one remained stable and one showed a slight increase in sTILs. The iTILs dispersion increased significantly in these patients (from 40 to 90 and 10 to 280, respectively). A corresponding spatial analysis of sTILs is ongoing. Additionally, qmIF and transcriptomic analysis of tumor-associated and immune genes is currently underway to compare biopsy and surgical specimens. Conclusion: In this preliminary analysis, we observe preoperative pembrolizumab-induced increases in sTILs with increased mean dispersion of iTILs in treatment naïve TNBC. Our initial analysis in this ongoing trial appears promising after examining changes in both the density and spatial structure of TILs. Further investigation is warranted to elucidate the impact of preoperative pembrolizumab in the TME of early stage TNBC and other potential therapeutic implications. Citation Format: Rami Vanguri, Hua Guo, Shuobo Boboila, Tahsin Kurc, Han Le, Shahira Abousamra, Le Hou, Dimitris Samaras, Rajarsi Gupta, Joel Saltz, Kevin Gardner, Hanina Hibshoosh, Kevin Kalinsky, Eileen Connolly. Preoperative pembrolizumab increases sTILs in treatment naïve stage I/IIA TNBC patients in a window of opportunity trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-09-17.

The Impact of Margin Status on Breast Conservation Rates.

Contemporary data indicate that breast conservation treatment (BCT) results in superior survival outcomes compared with mastectomy. However, positive margins after lumpectomy have implications for local control, and re-excisions are recommended to achieve negative margins. The need for reoperations after an initial attempt at BCT is associated with higher chance of conversion to mastectomy. Achieving negative margins at the first therapeutic surgical procedure is therefore critical to optimise BCT rates and survival outcomes. A compilation of scientific reports on BCT, margin status, rates of reoperation, and the impact on BCT rates was reviewed. Re-excision rates after initial lumpectomy is variable to a staggering degree and reported to be between 0 and 100%. High reoperation rates (ROR) are associated with higher likelihood of conversion to mastectomy, which may not confer favourable treatment outcomes. Although widely agreed that decreasing ROR is a desirable objective, there is controversy regarding the need for its urgent implementation as a quality metric. Critics of this cite challenges related to how this can be achieved and its attendant ramifications. On the other hand, without the appropriate incentive for quality improvement of surgical treatment of breast cancer, patients may be subject to poorer overall outcomes. Techniques and approaches are discussed in this article to enable a reduction in positive margin status, and therefore ROR. The rationale for achieving ROR of 10-20% are explicated, as well as the impact this would have on BCT rates, which translates to better survival outcomes for women with breast cancer.

Does every woman presenting with malignant calcifications require a post lumpectomy mammogram?

Successful breast-conserving surgery (BCS) followed by radiation therapy (XRT) is dependent on complete removal of the cancer with clear surgical margins, providing survival rates equivalent to those observed following mastectomy. In patients who have cancers presenting with microcalcifications, post lumpectomy mammograms (PLM) prior to radiation (XRT) can be performed to ensure that no cancer has been left behind. The purpose of this study was to assess the benefit of PLM in patients with malignant breast tumors presenting with microcalcifications. In this IRB-approved retrospective study, we reviewed medical records for patients with breast cancers presenting with microcalcifications who underwent BCS between February 2008 and June 2013. 198 patients who had a PLM prior to XRT for cancers presenting with microcalcifications were included. Histopathology of the initial lumpectomy revealed invasive carcinoma in 78/198 (39.4%) and DCIS alone in 120/198 (60.6%). 114/198 (58%) patients had negative surgical margins. 7/114 (6%) patients with negative margins had positive PLM and re-excisions that were positive for malignancy: sensitivity 88%, specificity 95%, PPV 58%, NPV 99%. 84/198 patients had positive surgical margins. The diagnostic performance of PLM in this group was: sensitivity 55%, specificity 71%, PPV 66%, NPV 61%. PLM plays an important role in the evaluation of patients undergoing breast conservation for breast cancer presenting with microcalcifications. Residual malignancy was detected on positive PLM in 6% of patients with negative margins.