Abstract BACKGROUND: It is known that breast cancer subtype (e.g., luminal vs. triple negative (TN)) can affect response to systemic therapy and prognosis; however, it is less well-understood whether these subtypes affect margin status and should therefore alter surgical management. METHODS: Data from two randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. The data were restricted to patients who had invasive carcinoma present in the PM specimen, and in whom data for all three receptors (ER, PR and HER-2) were known. Patients were classified as luminal if they were ER and/or PR+, HER-2 enriched if they were ER and PR negative but HER-2 positive, and TN if they were negative for all three receptors. We evaluated the impact of subtype on the margin status at the time the surgeon had completed their standard PM, prior to randomization to CSM vs. no CSM. Non-parametric statistical analyses were performed using SPSS Version 26. RESULTS: 350 patients were included in this cohort for analysis. The median patient age was 64 (range; 32-94 years) and the median invasive tumor size was 1.2 cm (range; 0.6-8.0 cm). 326 (93.1%) were luminal type, 22 (6.3%) were triple negative, and 2 (0.6%) were HER-2 enriched. Subtype was significantly correlated with race (black patients were more likely to have TN disease than white patients, 22.2% vs. 3.8%, p=0.001), palpability (TN tumors were more likely to be palpable than luminal cancers 54.5% vs. 29.8%, p=0.007) and grade (78.9% of TN cancers were high grade vs. 13.5% of luminal cancers p<0.001). Subtype did not correlate with Hispanic ethnicity, node positivity, nor lymphovascular invasion (p>0.05 for all). While patients with TN and HER-2 enriched tumors were more likely to receive neoadjuvant therapy, this did not reach statistical significance (p=0.117). Surgeons were no more likely to take selective margins on the basis of molecular subtype (p=0.413). 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=0.425). On multivariate regression controlling for molecular subtype, race, grade and palpability, the only factor which predicted positive margin status was grade (p=0.005), with high grade tumors being significantly more likely to have a positive margin than low grade tumors, independent of other factors (OR=3.503, 95% CI: 1.638-7.494, p=0.001). CONCLUSION: While molecular subtype correlates with race, tumor grade and palpability, it does not predict margin status. Therefore, molecular subtype should not, independent of other factors, influence surgical decision-making. Citation Format: Andrew Fenton, Elisabeth Dupont, Theodore Tsangaris, Carlos Garcia-Cantu, Marissa Howard-McNatt, Akiko Chiba, Adam Berger, Edward Levine, Jennifer Gass, Kristalyn Gallagher, Sharon Lum, Ricardo Martinez, Alliric Willis, Sonali Pandya, Eric Brown, Amanda Mendiola, Mary Murray, Naveenraj Solomon, Maheswari Senthil, David Ollila, David Edmonson, Melissa Lazar, Jukes Namm, Fangyong Li, Meghan Butler, Noreen McGowan, Maria Herrera, Yoana Avitan, Brian Yoder, Laura Walters, Tara McPartland, Victor Haddad, Hongwei Ma, Ming Xie, Anees Chagpar. Does breast cancer subtype impact margin status in patients undergoing partial mastectomy? [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-15.

BACKGROUND: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.METHODS: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.RESULTS: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).DISCUSSION:Molecular subtype does not predict margin status. Therefore, molecular subtype should not, independent of other factors, influence surgical decision-making.

Objective: Single-center studies have demonstrated that resection of cavity shave margins (CSM) halves the rate of positive margins and re-excision in breast cancer patients undergoing partial mastectomy (PM). We sought to determine if these findings were externally generalizable across practice settings. Methods: In this multicenter randomized controlled trial occurring in 9 centers across the United States, stage 0-III breast cancer patients undergoing PM were randomly assigned to either have resection of CSM ("shave" group) or not ("no shave" group). Randomization occurred intraoperatively, after the surgeon had completed their standard PM. Primary outcome measures were positive margin and re-excision rates. Results: Between July 28, 2016 and April 13, 2018, 400 patients were enrolled in this trial. Four patients (2 in each arm) did not meet inclusion criteria after randomization, leaving 396 patients for analysis: 196 in the "shave" group and 200 to the "no shave" group. Median patient age was 65 years (range; 29-94). Groups were well matched at baseline for demographic and clinicopathologic factors. Prior to randomization, positive margin rates were similar in the "shave" and "no shave" groups (76/196 (38.8%) vs. 72/200 (36.0%), respectively, P = 0.604). After randomization, those in the "shave" group were significantly less likely than those in the "no shave" group to have positive margins (19/196 (9.7%) vs. 72/200 (36.0%), P < 0.001), and to require re-excision or mastectomy for margin clearance (17/196 (8.7%) vs. 47/200 (23.5%), P < 0.001). Conclusion: Resection of CSM significantly reduces positive margin and re-excision rates in patients undergoing PM.

Abstract INTRODUCTION: Routine resection of cavity shave margins has been shown in single center studies to result in a significant reduction in positive margin and re-excision rates. In this prospective multicenter randomized controlled trial, we sought to validate these findings across practice settings. METHODS: Nine centers across the United States, varying in practice setting and patient population, participated in this clinical trial of 398 stage 0-III breast cancer patients undergoing partial mastectomy (with or without resection of selective cavity margins). Participants were stratified by clinical stage and randomized 1:1 to either have routine cavity shave margins resected (“shave”) or not (“no shave”). Randomization group was revealed to the surgeon intraoperatively, after they had completed their standard partial mastectomy and were ready to close. Positive margins were defined as “tumor at ink” for invasive cancer or within 2 mm for ductal carcinoma in situ (DCIS). Adverse events were defined as seromas requiring percutaneous drainage, and/or hematomas or abscesses requiring operative intervention. RESULTS: Median patient age was 65 (range; 29-94). 116 patients had invasive disease, 74 had DCIS, 179 had both, and 29 had no residual cancer at the time of partial mastectomy. The median invasive cancer size was 1.2 cm (range; 0.05-8.00 cm); the median extent of DCIS was 0.9 cm (range; 0.05-6.40 cm). The “shave” and “no shave” groups were well matched at baseline for clinicopathologic and demographic factors. FactorShave (n=197)No Shave (n=201)p-valueAge (years); median (range)67 (36-94)64 (29-89)0.585Race 0.062-- White173 (87.8%)164 (81.6%) -- Black20 (10.2%)33 (16.4%) -- Asian2 (1.0%)2 (1.0%) -- Native American0 (0%)2 (1.0%) -- Unknown/Declined2 (1.0%)0 (0%) Hispanic ethnicity28 (14.2%)32 (15.9%)0.806Invasive tumor size (cm); median (range)1.30 (0.09-8.00)1.20 (0.05-7.50)0.282DCIS extent (cm); median (range)0.80 (0.10-6.40)1.00 (0.05-5.50)0.906Invasive histology 0.556-- Ductal177 (89.8%)186 (92.5%) -- Lobular16 (8.1%)13 (6.5%) -- Mucinous3 (1.5%)2 (1.0%) -- Other1 (0.5%)0 (0%) Neoadjuvant therapy15 (7.6%)19 (9.5%)0.592Palpable tumor57 (28.9%)56 (27.9%)0.825Node positive*24 (16.3%)16 (10.6%)0.175*Of the 298 patients who had lymph nodes evaluated Prior to randomization, positive margin rates were similar in the “shave” and “no shave” groups (38.1% vs. 37.3%, respectively, p=0.918). After randomization, however, those in the “shave” group were significantly less likely than those in the “no shave” group to have positive margins (8.6% vs. 37.3%, respectively, p<0.001). They were also less likely to require re-excision or mastectomy for margin clearance (8.6% vs. 23.9%, p<0.001). There were no significant differences between the two groups in terms of adverse events (p=0.280). Rates of seroma (1.5% vs. 0.5%, p=0.368), hematoma (0.5% vs. 0.5%, p=1.000) and abscess (0.3% vs. 0%, p=0.495) were similar between the “shave” and “no shave” groups, respectively. CONCLUSION: Resection of cavity shave margins significantly reduces positive margin and re-excision rates in patients with stage 0-III breast cancer undergoing partial mastectomy. Citation Format: Chagpar AB, Tsangaris T, Garcia-Cantu C, Howard-McNatt M, Chiba A, Berger AC, Levine E, Gass JS, Gallagher K, Lum SS, Martinez RD, Willis AI, Pandya SV, Brown EA, Fenton A, Mendiola A, Murray M, Haddad V, Solomon NL, Senthil M, Bansil H, Ollila D, Snyder SK, Edmonson D, Lazar M, Namm JP, Li F, Butler M, McGowan NE, Herrera ME, Avitan YP, Yoder B, Dupont E. Does resection of cavity shave margins result in lower positive margin and re-excision rates in patients with stage 0-III breast cancer? Results from a prospective multicenter randomized controlled trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD8-07.