Abstract P3-20-01: Increased distant recurrence following margin involvement in early invasive breast cancer in two large UK cohorts

Abstract

Abstract Involved margins after surgery for early breast cancer increase the risk of local recurrence (LR), but international guidelines suggest that’ no tumour’ on ink is sufficient margin clearance after breast conserving surgery (BCS). Data on the effect of margin clearance on distant recurrence (DR) are lacking. Our aim was to determine the association between margin involvement, recurrence (DR) and breast cancer deaths. Methods Data from breast cancer units in Greater Manchester (GM) and the UK National Cancer Registry (NCRAS) were analysed. Margin status was prospectively recorded after surgery according to National Health Service Breast Screening Pathology (NHSBSP) minimum pathology data standards All patients underwent curative surgery and received adjuvant therapy according to local guidelines. Patients not undergoing curative surgery(T4, inflammatory or metastatic cancer) were excluded .Cox-proportional hazards models investigated factors associated with LR, DR and risk of breast cancer death.NCRAS records breast cancer deaths . Results GM analysis included 3270 patients from 2010 to 2014, 2295 (70.2%) had margins (>2mm) ,302 (9.2%) close (1-2mm) margin clearance and 673 (20.6%) involved (<1mm) margins. Median age was 61 years (range 24-100 years) and median follow up was 64.4 months (range 0.0-126.6 months). Breast Conserving Surgery (n=2030) and Mastectomy (n=1240) surgery was used as appropriate and most patients underwent adjuvant radiotherapy (71%) and/or hormone therapy (84%).160 patients (4.9%) developed LR and 231 patients (7.06%) DR. Time-to-DR (p=0.035) and time-to-LR (p=0.012) differed by margin status. At 5-years, the probability of LR was 3.1%, 3.5% and 5.8% and for DR was 4.9%, 5.9% and 7.1% for clear, close and involved margins, respectively. After multivariable adjustment, involved margins<1mm were associated with increased hazard of DR (HR 1.459, 95% CI: 1.050, 2.027, p=0.025) and LR (HR 1.79, 95% CI: 1.21, 2.63, p=0.004) compared to a clear margin>2mm. For Breast Conservation margins<1mm increased DR (HR 2.09,1.22-3.58:p<0.009 ) compared to clear margins. Similar findings were found in several subgroup analyses including screening, symptomatic and by cancer treatments. NCRAS data from 2010-2013 included 40,849 patients with invasive cancer of whom 27,589 margins >1mm (67.5%) and 3,935 (9.6%) were classed as “clear margins” and 9,325 (22.8%) cancer patients had involved margins <1mm, There were 3,160 deaths from breast cancer with a median follow-up of 80.2 months. Multivariate analysis in NCRAS indicated excess cancer mortality (HR 1.18 (95% CI 1.08-1.28) in the 9325 (22.8%) patients with margins <1mm (p<0.001), tumour stage (stage 3 HR 7.01 (6.28-7.82), p<0.001), age (HR 1.02 (1.02-1.03, p<0.001), symptomatic detection (HR 2.21 (1.98-2.46), p<0.001) and lower socio-economic status HR 1.31 (1.16-1.47, p<0.001). Conclusions Margins>1mm were associated with reduced DR and should be essential surgical management. Current guidelines about surgical margins need to be re-evaluated to achieve reduced DR and cancer deaths. Citation Format: Nigel James Bundred, Sarah Michael, John Broggio, Anne Armstrong, Glen Martin, Mohamed Absar, Jane Ooi. Increased distant recurrence following margin involvement in early invasive breast cancer in two large UK cohorts [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 P3-20-01.