Abstract

Abstract Background: Leaving involved margins after surgery for early breast cancer is associated with an increased risk of local recurrence but the effect on distant recurrence is controversial. ASCO and ASTRO endorsed a policy that negative margins of no ink on tumour represented sufficient margin for local control and that the routine practice of obtaining a more widely negative margin was not indicated. We aimed to assess margin status (<1mm, 1-2mm and clear margins >2mm) on local and distant control of breast cancer in a consecutive UK patient audit of Breast Cancer Units. Methods: Patients (n = 2795) undergoing surgery for early breast cancer (Tis, T1-3) in 3 Greater Manchester Breast Units had margin status prospectively recorded (reported by micrometer according to NHSBSP pathology guidelines) and local and distant recurrence recorded. All patients received adjuvant therapy according to local guidelines. Statistical analysis using cox proportional hazard regression was used to identify clinicopathological factors predicting recurrence in the multivariate analysis. Results: Overall 575 women (19.3%) had involved (≤1mm clearance) and 235 (8.5%) close (≤2mm clearance) and 1895 clear surgical margins. 1652 patients underwent breast conserving surgery and 1143 mastectomy. Median follow-up is 63.7 months. Overall local recurrence rate was 3.8% and distant recurrence 4.9% by a median of 5 years follow-up. Local and distant recurrence was higher after mastectomy at 7% and 7.8%, respectively. Margin <1mm was associated with increased local and distant recurrence compared to a clear margin >2mm. In multivariate analysis, two factors: molecular phenotype (other phenotypes versus Luminal A HR 1.79) and close / involved margins less than 2mm clearance (versus clear >2mm) [HR 1.76 (95% confidence intervals 1.06 - 2.92)], predicted local recurrence and the same factors together with mastectomy (compared to breast conservation), T and N stage predicted distant recurrence (see table 1). Table 1. Multivariate analysis of factors predicting cancer recurrenceLocal Recurrence (HR)Distant Recurrence (HR)Margin categorical <1mm vs >2mm1.84 (1.05 - 3.22, p=0.031)1.82 (1.1 – 3.02, p= 0.019)Margin <2mm (vs clear >2mm)1.76 (1.06-2.92, p=0.027)1.86 (1.16-2.27, p=0.009)T Stage 2 vs 11.55 (0.88 – 2.73, p=0.129)4.35 (2.07 – 9.14, p<0.001)T Stage 3 vs 11.66 (0.63 – 4.37, p=0.296)4.66 (1.85 – 11.72, p=0.001)N Stage 1 vs 01.74 (0.98 – 3.06, p=0.054)1.161 (0.97 – 2.87, p=0.06)N Stage 2 vs 01.69 (0.75 – 3.8, p=0.201)2.11 (1.07 - 4.17, p=0.03)N Stage 3 vs 02.07 (0.9 – 5.61, p=0.148)6.22 (3.32 – 11.68, p<0.001)Mastectomy vs WLE1.57 (0.91 – 2.72, p=0.103)2.51 (1.41 – 4.17, p=0.002)Luminal A vs Basal-Like0.25 (0.13 – 0.49, p<0.001)0.18 (0.09 – 0.37, p<0.001)Luminal B vs Basal-Like0.37 (0.2 – 0.68, p=0.001)0.33 (0.18 – 0.59, p<0.001)HER-2 vs Basal-Like0.1 (0.01 – 0.75, p=0.024)0.46 (0.19 – 1.15, p=0.095) Conclusion: Clearing surgical margins improves recurrence free survival (both local and distant). Leaving margins ≤2mm increases distant cancer recurrence and clearance of margins should be essential surgical management, particularly in oestrogen receptor (ER) negative breast cancer. Current guidelines accepting margins ≤1mm will increase distant recurrence and deaths from breast cancer. Citation Format: Sarah Michael, Sarah Bowers, Jane Ooi, Mo Absar, James Bundred, Nigel Bundred. Surgical margin involvement (<2mm) increases local and distant cancer recurrence [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-05.

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