Abstract P3-18-07: Margin involvement in invasive breast cancer leads to increased distant recurrence after breast conservation: Systematic review

Abstract Background: International guidelines state that any post-surgical tumour margin wider than tumour on ink following breast conserving surgery (BCS) for early invasive breast cancer is acceptable, based on analyses of margin width and local recurrence(LR). The aim of this review is to determine if margin involvement is associated with distant recurrence and secondarily to determine a minimum surgical margin to minimize both LR and distant recurrence (DR). Methods: A systematic review of literature published up to January 2021 was conducted according to PRISMA guidelines (PROSPERO: CRD42021232115). Unpublished data were sought from authors. The association between pathological margin status and distant and local recurrence were considered using random effects modelling. Results: Sixty-nine studies comprising 103,806 breast cancer patients were included. Across all studies, 9.7% of patients had tumour on ink and 13.9% had tumour on ink or a close margin (<2mm). Patients with positive margins had a distant recurrence rate of 33.1%, whilst patients with positive/close margins had a distant recurrence rate of 10.4% and patients with negative margins had a distant recurrence rate of 7.3%. Positive margins (tumour on ink) were associated with increased DR and LR on multivariable analyses (Hazard ratio (HR): 2.10, (95% Confidence interval (CI) 1.65-2.69, p<0.001)) and HR: 2.04, (95%CI: 1.75-2.38), p<0.0011) respectively, compared to negative margins. Close margins (no tumour on ink, but tumour < 2mm from ink) were associated with increased distant recurrence compared to wide margins (>2mm) (HR: 1.38, 95%CI: 1.13-1.69, p<0.001). In the 5 studies published after 2010, positive margins were associated with increased distant recurrence (HR:2.41 95%CI:1.81-3.21, p<0.001) as were positive or close margins compared to wide margins(HR:1.44 , 95%CI:1.22-1.71, p<0.001). Conclusions: Clear surgical margins after breast conserving surgery for early invasive breast cancer are associated with increases in distant disease free survival and also reduced LR. Increased distant recurrence with close, but not positive margins, suggests a minimum clear distance of 2mm is necessary. It is likely this relationship is causal and international guidelines should be reviewed. Distant recurrence models by margin statusDistant RecurrenceHazard ratio95% CIp-valuePositive versus Negative margins2.101.65-2.69<0.001Positive or Close versus Negative margins1.351.16-1.57<0.001Close versus Negative margins1.381.13-1.690.001 Citation Format: James R Bundred, David Dodwell, Ramsay Cuttress, Sarah Michael, Beth Stuart, Bernd Holleczek, Kerri Beckmann, Jane Dahlstrom, Nigel J Bundred. Margin involvement in invasive breast cancer leads to increased distant recurrence after breast conservation: Systematic review [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 P3-18-07.