Abstract Introduction: Positive lumpectomy margins are associated with an increased risk for ipsilateral tumor recurrence, and necessitate additional procedures to achieve acceptable margins. Re-excision rates are higher in patients with ductal carcinoma in situ (DCIS) versus those with invasive carcinoma. The purpose of this study was to investigate the clinicopathologic characteristics, surgical techniques, and other outcomes associated with re-excision over time following primary breast conserving surgery for DCIS. Methods: Our institutional Breast Cancer Database was queried for patients treated with lumpectomy as the primary procedure for pure DCIS from 2010-2021. Cases of microinvasive disease were excluded. The primary endpoint was the rate of re-excision following lumpectomy. Variables of interest included patient demographics and clinicopathologic characteristics. As a secondary analysis, adjusted odds ratios for the association of MarginProbe® with re-excisions were calculated using a multivariable logistic regression model controlling for age, tumor size, breast density and DCIS subtype. Individual comparisons of continuous variables were based on t-tests, group proportions compared with one-way ANOVA, and categorical variables compared using Chi Square tests. Results: Out of a total of 695 patients in our cohort, 221 (32%) had re-excisions. There was a statistically significant 2% decline per year in the number of re-excisions (p=0.005). Patients who underwent re-excision had larger size of DCIS (2.37 cm vs 1.37 cm, p<0.001). Papillary-type DCIS was associated with an increased rate of re-excision surgery (Table 1). Prior to the introduction of the MarginProbe® for intraoperative margin assessment in 2014, approximately 42% of patients with DCIS underwent re-excisions. This decreased to 24.9% in the post-2013 time frame (p=0.02). In an unadjusted estimate for the odds ratio for association, patients who underwent lumpectomy with MarginProbe® were 81% less likely to require re-excision (OR = 0.19, 95% CI = 0.12, 0.31, p<0.0001). In a logistic regression model controlling for potential confounders with re-excision as the dependent variable and MarginProbe® as the primary explanatory variable, patients for whom the MarginProbe® was used were 66% less likely to require re-excision when controlling for age, tumor size, menopausal status, breast density, and pathology (OR = 0.34, 95% CI 0.16, 0.69). Of patients who required re-excision, 20% went on to mastectomies as their second procedure. After each unsuccessful re-excision, a larger proportion of patients converted to mastectomy. In total, 26% of patients who had unsuccessful primary surgery went on to mastectomies. Of patients who proceeded to mastectomy as their second procedures, 13% were found to carry BRCA1 or 2 mutations. Conclusions: In our study of patients diagnosed with pure DCIS and treated with primary breast conserving surgery, larger size of DCIS and papillary subtype were associated with an increased rate of re-excision procedures. A proportion of patients with unsuccessful primary lumpectomies required multiple procedures to complete their surgical treatment and 26% went on to mastectomy. Patients whose primary procedures included intraoperative margin assessment with the MarginProbe® were significantly less likely to require re-excision. Intraoperative margin assessment is an important tool that can support breast conserving surgery in the challenging population of patients with DCIS. Table 1.Clinicopathologic CharacteristicsVariableNo Re-excision (n=313)Re-Excision (n=100)P-ValueAge; mean (SD)61.48 (12.01)58.04 (13.39)0.016Age of Menopause; mean (SD)50.22 (5.18)48.13 (5.45)0.004Size of DCIS; mean (SD)1.37 (1.25)2.37 (2.00)<0.001Breast Density (%)0.149N/A6 (1.9)2 (2.0)Entirely Fatty10 (3.2)3 (3.0)Extremely Dense19 (6.1)13 (13.0)Heterogeneously Dense165 (52.7)42 (42.0)Scattered Fibroglandular113 (36.1)40 (4.0)DCIS SubtypePapillary93 (29.7)48 (48.0)0.001Cribiform206 (65.8)69 (69.0)0.641Solid190 (60.7)60 (60.0)0.994Comedo54 (17.3)25 (25.0)0.117Surgical Margins (%)<0.001Close (>0 and <1mm)3 (1.0)60 (60.0)Negative (≥1 mm)310 (99.0)13 (13.0)Positive (≤0 mm)0 (0.0)27 (27.0) Citation Format: Joshua A Feinberg, Charles DiMaggio, Nakisa Pourkey, Jennifer Chun Kim, Jenny Goodgal, Amber Guth, Deborah Axelrod, Freya Schnabel. Meeting the challenge of successful one-stage lumpectomy for DCIS [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 P3-18-11.