Shave Margins Research Articles

Is the Number or Proximity of Margins Less than 2 mm Associated with an Increased Mastectomy Rate in Patients Attempting Breast Conservation Therapy for Ductal Carcinoma In Situ?

Consensus guidelines recommend ≥ 2 mm margins in patients undergoing partial mastectomy (PM) for ductal carcinoma in situ (DCIS). It is unknown whether the number or proximity of margins less than 2 mm is associated with an increased mastectomy rate in patients attempting breast conservation therapy (BCT) for DCIS. The aim of this study is to examine this relationship. An institutional database review identified 208 patients with DCIS who underwent PM at a tertiary referral center and community hospitals from July 2020 to June 2023. Patients with a history of breast cancer, previous surgery for breast cancer, ipsilateral invasive carcinoma, papillary carcinoma, Paget's disease, more lobular carcinoma in situ (LCIS) than DCIS present, initial mastectomy, no DCIS present, routine shave margins (of all vectors), and ≥ 2 mm margins of all six vectors were excluded. Selective intraoperative margin re-excisions were included. A total of 208 patients who met inclusion criteria were retrospectively reviewed. 122 (25%) had one close/positive (< 2 mm) margin and 86 (18%) had two or more close/positive margins. Of the patients with one close/positive margin, 7% (9/122) eventually underwent mastectomy. Of the patients with two or more close/positive margins, 20% (17/86) eventually underwent mastectomy. Overall, no patients with opposing margins underwent mastectomy. Patients undergoing PM for DCIS have a mastectomy rate that is increased threefold, with two or more close/positive margins at initial PM, when compared with those with only one close/positive margin. The presence of opposing close/positive margins at initial PM did not increase the mastectomy rate and most were cleared with re-excision.

Impact of cavity shave margins in patients with ductal carcinoma in situ undergoing conserving breast surgery.

The main challenge during breast-conserving surgery (BCS) is to obtain clear margins, especially in patients with ductal carcinoma in situ (DCIS) due to the absence of well-defined nodules. Many surgical approaches have been used in an attempt to reduce the positive margin rate. The aim of this retrospective study is to compare the cavity shave margin technique with standard surgery and the intraoperative evaluation of surgical margins. This is a single-center retrospective study analyzing margin status, need for re-excision, and surgical time in a cohort of 227 patients who underwent surgery from September 2016 to September 2022. In patients subjected to cavity shaving, we reported a significant reduction in positive margins of 17.1% versus 28.7% (p-value = 0.042). Also, a difference in terms of surgical re-excision was reported as p-value = 0.039 (12.4% versus 23.8%, respectively, for the cavity shave and control group). In the multivariate analysis, intraoperative evaluation of the margins was a risk factor for margins re-excision (Wald = 4.315, p = 0.038, OR: 2.331 [95% CI: 1.049-5.180]). Surgical time was lower in patients subjected to cavity shaves (p = 0.024), and the relative mean time was 68.4 min ± 37.1 min in the cavity shave group versus 93.9 min ± 40.6 min in the control group. The cavity shave margin technique in conserving breast surgery results in a reduction in positive margin rate, surgical re-excision, and operative time.

How far are we off? Analyzing the accuracy of surgical margin relocation in the head and neck.

Positive surgical margin rates remain high in head and neck cancer surgery. Relocation is challenging given the complex, three-dimensional (3D) anatomy. Prospective, multi-institutional study to determine accuracy of head and neck surgeons and pathologists relocating margins on virtual 3D specimen models using written descriptions from pathology reports. Using 3D models of 10 head and neck surgical specimens, each participant relocated 20 mucosal margins (10 perpendicular, 10 shave). A total of 32 participants, 23 surgeons and 9 pathologists, marked 640 margins. Of the 320 marked perpendicular margins, 49.7% were greater than 1 centimeter from the true margin with a mean relocation error of 10.2 mm. Marked shave margins overlapped with the true margin a mean 54% of the time, with no overlap in 44 of 320 (13.8%) shave margins. Surgical margin relocation is imprecise and challenging even for experienced surgeons and pathologists. New communication technologies are needed.

Abstract PO2-03-03: The Significance of Cavity Shave Margins in Breast Carcinoma on Margin Status and Re-excision Rates

Abstract Context: The comparative outcomes of breast conserving surgery (BCS) with and without cavity shave margins are not well established. We aim to evaluate the impact of each procedure on final margin status and rate of re-excision. Design: A total of 529 breast cancer cases from our institution between 2013-2015 were included. Demographic and clinicopathological data including procedure type, tumor type, grade, margins status, and re-excision rates were collected. H&amp;E slides of positive margins (tumor on ink) were reviewed by two pathologists. Appropriate statistical analysis was performed. Results: Out of 529 breast cancer cases, 125 were Ductal Carcinoma in situ (DCIS), 152 were Invasive Ductal Carcinoma (IDC) and 252 had both pathologies. The median age of patients was 59 years (range: 24-90). Patients who underwent excision with shave margins were 162 (35 DCIS, 56 IDC, 71 both) while excision without shave margins were 367 (90 DCIS, 96 IDC, 181 both). Re-excision rates were significantly lower 1) in patients who underwent BCS with cavity shave margins compared to those without (OR 0.32, p&amp;lt; 0.001) and 2) in patients who did not require lymph node excision compared to those who did (OR 4.26, p&amp;lt; 0.001). Additionally, patients who had DCIS had a higher rate of re-excision than those with invasive cancer only (OR 5.17, P&amp;lt; .001). After adjusting for type of tumor, patients who underwent cavity shaving compared to those who did not, no significant difference was seen in tumor at margins (OR 0.73, p=0.282) or tumor within 2mm (OR 1.14, p=0.512) from margins. However, patients with IDC who underwent cavity shave had a higher proportion of negative tumor at the margins (76.5% vs. 67.0%; p=0.051). We found that patients who had an invasive carcinoma (IC) had a lower risk of having tumor at the margin or within 2 mm from the margin than those with DCIS or DCIS+IC, (p&amp;lt; .05). Conclusions: Our data shows that BCS with cavity shave margins is superior with regards to negative margin and re-excision rates when compared to without cavity shave margins. Citation Format: Fadi Zaiem, Anna Numi, Mira Kheil, Asem AbuJamea, Deepti Jain, Omar Abbas, Lauren Larson, Noor Suleiman, Saleh Al-Juburi, Sanaa Awada, Ragad Almsaddi, Hyejeong Jang, Seongho Kim, Nagla Salem, Lydia Choi, Sudeshna Bandyopadhyay, Sunil Jaiman, Rouba Ali-Fehmi. The Significance of Cavity Shave Margins in Breast Carcinoma on Margin Status and Re-excision Rates [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 PO2-03-03.

Cavity Shave Margins in Breast Conservative Surgery a Strategy to Reduce Positive Margins and Surgical Time.

Background: Resection of additional tissue circumferentially around the cavity left by lumpectomy (cavity shave) was suggested to reduce rates of positive margins and re-excision. Methods: A single center retrospective study which analyzed margins status, re-excision, and surgical time in patients who underwent breast conserving surgery and cavity shave or intraoperative evaluation of resection margins. Results: Between 2021 and 2023, 594 patients were enrolled in the study. In patients subjected to cavity shave, a significant reduction in positive, focally positive, or closer margins was reported 8.9% vs. 18.5% (p = 0.003). No difference was reported in terms of surgical re-excision (p < 0.846) (5% vs. 5.5%). Surgical time was lower in patients subjected to cavity shave (<0.001). The multivariate analysis intraoperative evaluation of sentinel lymph node OR 1.816 and cavity shave OR 2.909 were predictive factors for a shorter surgical time. Excluding patients subjected to intraoperative evaluation of sentinel lymph node and patients with ductal carcinoma in situ, patients that underwent the cavity shave presented a reduced surgical time (67.9 + 3.8 min vs. 81.6 + 2.8 min) (p = 0.006). Conclusions: Cavity shaving after lumpectomy reduced the rate of positive margins and it was associated with a significant reduction in surgical time compared to intraoperative evaluation of resection margins.

Cost minimization in breast conserving surgery: a comparative study of radiofrequency spectroscopy and full cavity shave margins

BackgroundIn an effort to minimize positive margins and subsequent re-excision after breast conserving surgery (BCS), many providers and facilities have implemented either a Full Cavity Shave (FCS) approach or adding the MarginProbe Radiofrequency Spectroscopy System.ObjectiveWe sought to create a functioning Pro-Forma for use by facilities and payers to evaluate and compare the cost savings of implementing FCS or MarginProbe based on personalized variable inputs.MethodsA decision tree demonstrating three possible surgical pathways, BCS, BCS + FCS, and BCS + MarginProbe was developed with clinical inputs for re-excision rate, mastectomy as 2nd surgery, rate of reconstruction, and rate of 3rd surgery derived by a literature review. A surgical pathway cost formula was created using the decision tree and financial inputs derived by utilizing the nation’s largest database of privately billed health insurance claims and Medicare claims data (fairhealth.org). Using the surgical pathway formula and financial inputs, a customizable Pro-Forma was created for immediate cost savings analysis of BCS + FCS and BCS + Marginprobe using variable inputs. Costs are from the perspective of third-party payers.ResultsUtilizing MarginProbe to reduce re-excisions for positive margins can be associated with better cost-savings than FCS due to the increased pathology processing costs by using an FCS approach. The reduction in re-excision provided by both FCS and MarginProbe offset their increased expense to various degrees with cost savings of each method improving as baseline re-excisions rates increase, until ultimately each may become cost-neutral or cost-prohibitive when compared to BCS alone. Our data suggest that in the privately insured population, MarginProbe provides a cost-savings over BCS alone when baseline re-excision rates are over 20% and that FCS becomes cost-saving when baseline re-excision rates are over 29%. For Medicare patients, MarginProbe provides a cost-savings when baseline re-excision rates exceed 34%, and FCS becomes cost-saving for re-excision rates over 52%. Our Pro-Forma allows an individual provider or institution to evaluate the cost savings of the FCS approach and/or utilization of the MarginProbe device such that the additional cost or cost-savings of utilizing one or both of these methods can be quickly calculated based on their facility’s volume and baseline re-excision rate.ConclusionsOur data suggest that utilizing either an FCS approach or the MarginProbe radiofrequency spectroscopy system may be a cost-saving solution to reducing the rate of re-excisions depending on a facility or practice’s surgical volume and baseline re-excision rate. The degree to which each of these interventions provides an added cost or cost-savings to healthcare payers can be evaluated by utilizing the Pro-Forma outlined herein with customizable variable inputs.

Does Preoperative MRI Reduce Positive Margins after Breast-Conserving Surgery?

Breast-conserving surgery (BCS) is a mainstay for breast cancer management, and obtaining negative margins is critical. Some have advocated for the use of preoperative magnetic resonance imaging (MRI) in reducing positive margins after BCS. We sought to determine whether preoperative MRI was associated with reduced positive margins. The SHAVE/SHAVE2 trials were multicenter trials in ten US centers with patients with stage 0-3 breast cancer undergoing BCS. Use of preoperative MRI was at the discretion of the surgeon. We evaluated whether or not preoperative MRI was associated with margin status prior to randomization regarding resection of cavity with shave margins. A total of 631 patients participated. Median age was 64 (range 29-94) years, with a median tumor size of 1.3 cm (range 0.1-9.3cm). Patient factors included 26.1% of patients (165) had palpable tumors, and 6.5% (41) received neoadjuvant chemotherapy. Tumor factors were notable for invasive lobular histology in 7.0% (44) and extensive intraductal component (EIC) in 32.8% (207). A preoperative MRI was performed in 193 (30.6%) patients. Those who underwent preoperative MRI were less likely to have a positive margin (31.1% versus 38.8%), although this difference was not statistically significant (p = 0.073). On multivariate analysis, controlling for patient and tumor factors, utilization of preoperative MRI was not a significant factor in predicting margin status (p = 0.110). Rather, age (p = 0.032) and tumor size (p = 0.040) were the only factors associated with margin status. These data suggest that preoperative MRI is not associated margin status; rather, patient age and tumor size are the associated factors.

Does Non-Classic Lobular Carcinoma In Situ at the Lumpectomy Margin Increase Local Recurrence?

The clinical significance of nonclassic, lobular carcinoma in situ (NC-LCIS) at the surgical margin of excisions for invasive cancer is unknown. We sought to determine whether NC-LCIS at or near the margin in the setting of a concurrent invasive carcinoma is associated with risk of ipsilateral breast tumor recurrence (IBTR) and locoregional recurrence (LRR). Patients with stage 0-III breast cancer and NC-LCIS who underwent lumpectomy between January 2010 and January 2022 at a single institution were retrospectively identified. NC-LCIS margins were stratified as <2 mm, ≥2 mm, or within shave margin. Rates of IBTR and LRR were examined. A total of 511 female patients (median age 60 years [interquartile range (IQR) 52-69]) with NC-LCIS and an associated ipsilateral breast cancer with a median follow-up of 3.4 years (IQR 2.0-5.9) were identified. Final margins for NC-LCIS were ≥2 mm in 348 patients (68%), <2 mm in 37 (7.2%), and within shave margin in 126 (24.6%). Crude incidence of IBTR was 3.3% (n = 17) and that of LRR was 4.9% (n = 25). There was no difference in the crude rate of IBTR by NC-LCIS margin status (IBTR rate: 3.7% ≥2 mm, 0% <2 mm, 3.2% within shave margin, p = 0.8) nor in LRR (LRR rate: 4.9% ≥2 mm, 2.7% <2 mm, 5.6% within shave margin, p = 0.9). For completely excised invasive breast cancers associated with NC-LCIS, extent of margin width for NC-LCIS was not associated with a difference in IBTR or LRR. These data suggest that the decision to perform reexcision of margin after lumpectomy should be driven by the invasive cancer, rather than the NC-LCIS margin.

Risk Factors for Positive Margins in Breast-Conserving Surgery.

Introduction Breast-conserving surgery (BCS) followed by adjuvant radiotherapy has similar overall survival compared to mastectomybut is associated with higher rates of local recurrence. Positive surgical margins in BCS are the most important predictor of local recurrence. The aim of our study was to assess the risk factors associated with positive margins in women undergoing BCS for breast cancerin order to inform our clinical practice and minimize re-operation rates. Methods Patients with a diagnosis ofbreast cancer who underwent BCS from January 2013 to January 2021 were identified from our pathology database and included in the study. All patients underwent a lumpectomy with the removal of additional shaved cavity margins. Statistical analysis was used toassess the effect of patient clinical and pathological risk factors on the rate of positive margins. Results One hundred and twenty patients underwent BCS for breast cancer. Twenty-four percent of patients had positive margins. Of the 29 patients that underwent subsequent re-excisions, only 13 (45%) hadresidual disease in the re-excision specimen. In younger patients, tumors localized in lower quadrants and the presence of extensive intraductal component within invasive breast cancer increased the risk of positive margins. In addition, positive margins were encountered more significantly in patients with ductal carcinoma in situ (DCIS) compared to invasive tumors. Multivariate analysis showed that DCIS and young age were the only factors independently associated with positive margins. Conclusion DCIS and younger patients have a higher rate of positive margins during BCS than invasive breast cancer. For such patients at higher risk of positive margins, excision of cavity shave margins and intraoperative inking may be done to lower positive margin rates.Preoperative review of breast imaging, core biopsies, and counseling of patients about the likelihood of positive margins is important.

Shaves off the Cavity or Specimen in Lumpectomy for Breast Cancer.

Re-excision for positive margins (margins where tumor is positive) after breast conserving surgery (BCS) is common and burdensome for breast cancer patients. Routine shave margins can reduce positive margins and re-excision rates. Cavity shaving margin (CSM) removes margins from the lumpectomy cavity edges, whereas specimen shave margin (SSM) requires exvivo removal of margins from the resected specimen. We assessed breast cancer patients undergoing BCS who received CSM or SSM procedures from 2017 to 2019. CSM and SSM techniques were compared by analyzing positive rates of primary and final shaved margins, re-excision rates, and tissue volumes removed. Of 116 patients included in this study, 57 underwent CSM and 59 underwent SSM. Primary margins were positive or close in 19 CSM patients and 21 SSM patients (33% versus 36%; P=0.798). Seventeen CSM patients had a tumor in shaved margin specimens, compared to four patients for SSM (30% versus 7%; P<0.001); however, final shave margins were similar (5% versus 5%; P=0.983). Volumes of shave specimens were higher with SSM (40.7 versus 13.4cm3; P<0.001), but there was no significant difference in the total volume removed (146.8 versus 134.4cm3; P=0.540). For tumors 2cm or larger, the total volume removed (140 versus 206cm3; P=0.432) and rates of final margin positivity (7.5% versus 0%; P=0.684) were similar for both techniques. CSM and SSM are effective techniques for achieving low re-excision rates. Our findings suggest that surgeons performing either CSM or SSM may maintain operative preferences and achieve similar results.

249P Significance of intraoperative frozen assessment of cavity shave margins in patients undergoing breast conservation surgery: A tertiary care centre experience

Breast conservation surgery (BCS) is the preferred surgical treatment modality for eligible breast cancer patients. Oncological safety and aesthetic outcomes remain the primary objective of breast conservation surgery. Positive margin status following BCS needs revision surgery, which leads to increased patient anxiety, cost of treatment and delay in start of adjuvant treatment. We evaluated the significance and accuracy of intraoperative frozen section assessment of cavity shave margins (IOFSA) in patients undergoing BCS.

Preoperative MRI and Its Impact on Surgical Outcomes in Patients with Triple Negative Breast Cancer Treated with Primary Surgery: Did New Margin Guidelines or Cavity Shave Margins Practice Diminish the Role of Preoperative MRI?

Results of an earlier retrospective study from our institution suggested that patients with triple negative breast cancer (TNBC) who had preoperative MRI may have had an improved local recurrence rate (LRR) after breast conserving surgery (BCS). We aimed to clarify the impact of preoperative MRI on surgical outcomes in an expanded TNBC cohort treated by BCS in a contemporary era. Our study cohort comprised 648 patients with TNBC who underwent BCS between 2009 and 2018. Demographic and clinical characteristics were compared between those with (n=292, 45.1%) and without (n=356, 54.9%) preoperative MRI. Multivariable logistic regression was performed to assess the association of preoperative MRI with surgical outcomes. The crude LRR of 3.5% was lower than previously reported. Univariable analyses demonstrated that the LRR and re-excision rates in the MRI and no-MRI groups were 3.4 and 3.7%, 21.6% and 27.2%, p=0.876 and p=0.10, respectively. Multivariable logistic regression analyses demonstrated that preoperative MRI was not associated with a lower LRR: odds ratio (OR)=1.42 (p=0.5). During our study period, new margin guidelines and shave margins practice were adopted in 2014 and 2015. To account for their effects, the year of diagnosis/surgery and other clinical variables were adjusted in multivariable logistic regression and inverse probability weighting models to demonstrate that preoperative MRI remained associated with a lower re-excision risk, OR 0.56, p=0.04l; and a lower re-excision rate, 23.15% versus 36.0%, p<0.01, respectively. Our findings suggested that patients with TNBC anticipating BCS may benefit from preoperative MRI.

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 P3-19-19: Intraoperative Radiation Therapy (IORT) : A large integrated healthcare system’s approach and outcomes

Abstract Background: With TARGIT-R(Retrospective) showing a higher-than-expected ipsilateral breast tumor recurrence (IBTR) the community setting for intraoperative radiation therapy (IORT), we evaluated IORT outcomes in an integrated health care system.Methods: A retrospective review of early breast cancer patients who received IORT between February 2014-February 2020 was performed. IORT was offered at a single medical center within a large integrated healthcare system. Criteria for IORT included patients ≥50 years with T1, low to intermediate grade, endocrine-responsive HER2- invasive ductal carcinoma. All breast cancer patients were reviewed at weekly multidisciplinary breast conferences, and IORT was offered when patients met the eligibility criteria. Primary outcomes include IBTR, mortality, and complications. Results: Of 5,731 potentially eligible patients, 245 patients (4.3%) underwent IORT. Mean age was 65.4 ± 0.4 years with median follow-up 3.5 years ± 2.2 months. Based on American Society of Radiation Oncology guideline, 51% were suitable, 38.4% cautionary, and 10.6% unsuitable candidates based on the final pathology. The patients were reassigned to the cautionary group because of the margin width and/or extensive DCIS. Unintended boost (primary IORT followed by whole-breast radiation) was given in 6.5% of IORT patients. At median follow-up of 3.5 years, IBRT was 3.7% for all patients. There was one breast-cancer-related mortality (0.4%), and 7 mortality (2.9%) from other causes. Although not statistically significant, there was a trend towards higher recurrence in those not adherent with endocrine treatment than those who were (7.4% vs 1.9%, p=0.07). The overall complication rate was 14.7% with seroma as the most common.Conclusions: At 3.5-year follow-up, our IORT IBTR rate of 3.7%. Our protocol subsequently was modified to require all IORT patients to receive surgical shave margins, WBI for all cautionary patients on the final pathology, and requirement of endocrine treatment. Citation Format: Annie Tang, Jason Kelly, Elizabeth Cureton, Jonathan Svahn, Eva Thomas, Liisa Lyon, Veronica Shim. Intraoperative Radiation Therapy (IORT) : A large integrated healthcare system’s approach and outcomes [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 P3-19-19.

Does Breast Cancer Subtype Impact Margin Status in Patients Undergoing Partial Mastectomy?

Molecular subtype in invasive breast cancer guides systemic therapy. It is unknown whether molecular subtype should also be considered to tailor surgical therapy. The present investigation was designed to evaluate whether breast cancer subtype impacted surgical margins in patients with invasive breast cancer stage I through III undergoing breast-conserving therapy. Data from 2 randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. Patients were included if invasive carcinoma was present in the PM specimen and data for all 3 receptors (ER, PR, and HER2) were known. Patients were classified as luminal if they were ER and/or PR positive; HER2 enriched if they were ER and PR negative but HER2 positive; and TN if they were negative for all 3 receptors. The impact of subtype on the margin status was evaluated at completion of standard PM, prior to randomization to CSM versus no CSM. Non-parametric statistical analyses were performed using SPSS Version 26. Molecular subtype was significantly correlated with race (P = .011), palpability (P = .007), and grade (P < .001). Subtype did not correlate with Hispanic ethnicity (P = .760) or lymphovascular invasion (P = .756). In this cohort, the overall positive margin rate was 33.7%. This did not vary based on molecular subtype (positive margin rate 33.7% for patients with luminal tumors vs 36.4% for those with TN tumors, P = .425). Molecular subtype does not predict margin status. Therefore, molecular subtype should not, independent of other factors, influence surgical decision-making.

The Effect of Lumpectomy and Cavity Shave Margin Status on Recurrence and Survival in Breast-Conserving Surgery.

Cavity shave margins (CSMs) decrease rate of positive margins and need for re-excision. Recurrence data following breast-conserving surgery (BCS) are not always available in large cancer registries. We sought to define our recurrence and survival data in BCS with routine excision of CSMs. A single institution, 10-year retrospective review of breast cancer patients who underwent BCS with routine CSMs was conducted. Cavity shave margin technique was standard. Cox proportional hazard analyses and the Kaplan-Meier method were used to estimate recurrence and survival. Breast-conserving surgery with CSM was performed in 839 patients. Re-excision rate to achieve negative margins was 8.5%. Fifty-two patients (75%) underwent margin re-excision vs 18 patients (25%) underwent salvage mastectomy. Positive margin rate stratified by tumor histology was highest for invasive lobular carcinoma followed by mixed invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS), followed by pure DCIS and lowest for IDC. Length of follow-up was (4.7 ± 2.6, years). Overall recurrence rate (locoregional and systemic) was 4.3%: highest in patients with negative lumpectomy margin but positive CSM (L-S+ = 15%) followed by positive lumpectomy and CSMs (L+S+ = 14%), followed by patients with positive lumpectomy margin but negative CSMs (L+S- = 13%) and lowest for negative lumpectomy and CSM (L-S- = 5%), (P = .0008). There was no difference in 5-year breast cancer-specific survival between the 4 subgroups: 96% for L-S-, 86.7% L-S+, 94.7% L+S+ and 90% L+S- (P = .094). Recurrence following BCS with CSMs can be stratified based on both lumpectomy and cavity shave margin positivity. Routine excision of CSMs allows identification of these patient subsets.

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.

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.

Multi-magnification-based machine learning as an ancillary tool for the pathologic assessment of shaved margins for breast carcinoma lumpectomy specimens.

The surgical margin status of breast lumpectomy specimens for invasive carcinoma and ductal carcinoma in situ (DCIS) guides clinical decisions, as positive margins are associated with higher rates of local recurrence. The "cavity shave" method of margin assessment has the benefits of allowing the surgeon to orient shaved margins intraoperatively and the pathologist to assess one inked margin per specimen. We studied whether a deep convolutional neural network, a deep multi-magnification network (DMMN), could accurately segment carcinoma from benign tissue in whole slide images (WSIs) of shave margin slides, and therefore serve as a potential screening tool to improve the efficiency of microscopic evaluation of these specimens. Applying the pretrained DMMN model, or the initial model, to a validation set of 408 WSIs (348 benign, 60 with carcinoma) achieved an area under the curve (AUC) of 0.941. After additional manual annotations and fine-tuning of the model, the updated model achieved an AUC of 0.968 with sensitivity set at 100% and corresponding specificity of 78%. We applied the initial model and updated model to a testing set of 427 WSIs (374 benign, 53 with carcinoma) which showed AUC values of 0.900 and 0.927, respectively. Using the pixel classification threshold selected from the validation set, the model achieved a sensitivity of 92% and specificity of 78%. The four false-negative classifications resulted from two small foci of DCIS (1 mm, 0.5 mm) and two foci of well-differentiated invasive carcinoma (3 mm, 1.5 mm). This proof-of-principle study demonstrates that a DMMN machine learning model can segment invasive carcinoma and DCIS in surgical margin specimens with high accuracy and has the potential to be used as a screening tool for pathologic assessment of these specimens.

Breast-Conserving Surgeries With and Without Cavity Shave Margins Have Different Re-excision Rates and Associated Overall Cost: Institutional and Patient-Driven Decisions for Its Utilization

BackgroundReducing the rate of margin positivity and reoperations remains a paramount goal in breast-conserving surgery (BCS). This study assesses the effectiveness of standard partial mastectomy with cavity shave margins (CSM) compared with partial mastectomy with selective margin resection (SPM), with regard to outcomes of the initial surgeries, re-excisions, and overall costs. Patients and MethodsThis is a retrospective review of 122 eligible breast cancer patients who underwent BCS at one institution. The CSM and SPM groups each included 61 patients, matched for presurgical diagnoses and clinical stage. Data including margin status, rates and reason for re-excision, associated operation times, and costs were analyzed. ResultsPatients undergoing CSM had less than half the rate of positive margins (PMs) (10% vs. 23%; P = .03) and re-excisions (8% vs. 23%; P = .02) compared with SPM. In the former group, the margin involvement was focal, and re-excisions were performed almost exclusively for PMs. For SPM, the majority (92%) of PMs were on the main lumpectomy specimen rather than the selective margins, and re-excisions included, in addition to PMs, extensive or multifocal negative but close margins. Reduced breast tissue volumes were removed with CSM, particularly for patients undergoing a single surgery (47 vs. 165 cm3; P < .001). The initial surgery with CSM is on average 27% more costly than that for SPM (P < .001), due to the increased pathology costs which are partially offset by the increased re-excision rates in SPM. ConclusionCircumferential cavity shaving, associated with consistent lower PMs, tissue volumes excised, and re-excision rates, is appropriate for routine implementation as a method offering superior surgical outcomes.