Abstract PS01-10: Surgical margins in breast conserving surgery (BCS) for ductal carcinoma in-situ (DCIS) and clinical outcomes: significant associations with increased recurrence and overall survival

Abstract

Abstract Background: Optimal surgical margin in breast conserving surgery (BCS) for DCIS are not established, largely due to an absence of accurate margin data. A margin width of 2mm was adopted by the American College of Surgeons (ACS). The UK Association of Breast Surgery (ABS) recommended a 1mm margin. Conducting a randomized controlled trial to answer this question is unfeasible; therefore we used retrospective histological margin data from available datasets to assess whether there is an association between margin width and time to recurrence (TTR). Methods: Patients were included if aged >18 years with a new diagnosis of DCIS alone, between 2003-2014, within UK NHS Breast Screening Programme (BSP). Primary treatment included BCS and a minimum histological excision margin width recorded. Exclusion criteria included: i) prior history of DCIS; ii) prior history of invasive cancer or its diagnosis within 3 months of initial surgical treatment for DCIS. Data was extracted from English Cancer Registries (CR), ABS and Sloane audits. TTR was defined as time from diagnosis to local or distant recurrence. Cox regression was used to compare TTR by surgical margin width utilising a range of thresholds, with focus on < 1mm vs ≥1mm; < 2mm vs ≥2mm and ≥1- < 2mm vs ≥2mm. Patients with 0mm margin or where categorized as “clear/not stated” were excluded from these analyses. Models were adjusted for age group, DCIS grade and size, ER status, number of BCSs, radiotherapy (RT) received, diagnosis year and CR centre. Overall survival (OS) was a secondary endpoint. Results: 17,260 patients diagnosed with DCIS having BCS as definitive surgery were identified between 2003-2014; 679 (5%), 2105 (15%), 1339 (10%) and 9744 (70%) with recorded margins of >0- < 1mm, ≥1- < 2mm, ≥2- < 3mm and ≥3mm, respectively. 10,253 (59%) patients received RT and in 7,007 (41%) RT receipt was unknown. Overall, 14,004 (81%), 3,052 (18%) and 201 (1%) patients had one, two and ≥3 BCSs respectively; there was no significant change in these percentages over time (p=0.2 Cuzick test). Median follow-up time for the cohort was 8.2 years (IQR: 6.1-11.2). 2221 (13%) patients had a subsequent event: 1741/2221 (78%) invasive recurrence and 480/2221 (22%) DCIS alone. The annual event rate over 15 years of follow-up was relatively consistent at 1.2% per annum (pa) for margins ≥2mm versus 1.8% pa for margins < 2mm. A shorter TTR was observed for patients with surgical margins < 1mm vs ≥1mm (adjusted HR=1.30; 95%CI: 1.05-1.62; p=0.02); < 2mm vs ≥2mm (adjusted HR=1.20; 95%CI: 1.06-1.36; p=0.004) and ≥1- < 2mm vs ≥2mm (adjusted HR=1.20; 95%CI: 1.04-1.40; p=0.02). Margins >2mm did not appear to significantly improve TTR (adjusted HR=0.96; 95%CI: 0.85-1.08; p=0.50 for ≥5mm vs ≥2- < 5mm). Models also showed that risk of recurrence increased as the number of BCSs increased (adjusted HR=1.25; 95%CI: 1.10-1.43: p< 0.001 for 2 vs 1 and adjusted HR=2.03; 95%CI: 1.36-3.03: p< 0.001 for 3+ vs 1). In total, 1552 (9%) patients had died. OS appeared reduced for patients with surgical margins < 2mm vs ≥2mm (adjusted HR=1.25 (1.07-1.45); p=0.005) and for ≥1- < 2mm vs ≥2mm (adjusted HR=1.28 (1.07-1.54); p=0.008). Margins <2mm did not appear to significantly improve OS further (adjusted HR=1.06; 95%CI: 0.92-1.21; p=0.43 for ≥5mm vs ≥2- < 5mm). Conclusion: Patients with DCIS with histological margins of < 2mm, adjusted for other clinical factors, have significantly worse TTR and OS rates compared to margins ≥2mm; the increased annual event rate is consistent out to 15 years. More than 1 BCS is also associated with an increased risk of recurrence. These findings are important for the treatment of patients with DCIS. Citation Format: John Robertson, D Mark Sibbering, Sikhuphukile Ndebele-Mahati, Olive Kearins, Sarah Pinder, Ashu Gandhi, Judith Bliss, Lucy Kilburn. Surgical margins in breast conserving surgery (BCS) for ductal carcinoma in-situ (DCIS) and clinical outcomes: significant associations with increased recurrence and overall survival [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS01-10.