Objective To determine if margin involvement is associated with distant recurrence and to determine the required margin to minimise both local recurrence and distant recurrence in early stage invasive breast cancer. Design Prospectively registered systematic review and meta-analysis of literature. Data sources Medline (PubMed), Embase, and Proquest online databases. Unpublished data were sought from study authors. Eligibility criteria Eligible studies reported on patients undergoing breast conserving surgery (for stages I-III breast cancer), allowed an estimation of outcomes in relation to margin status, and followed up patients for a minimum of 60 months. Patients with ductal carcinoma in situ only or treated with neoadjuvant chemotherapy or by mastectomy were excluded. Where applicable, margins were categorised as tumour on ink (involved), close margins (no tumour on ink but <2 mm), and negative margins (≥2 mm). Results 68 studies from 1 January 1980 to 31 December 2021, comprising 112 140 patients with breast cancer, were included. Across all studies, 9.4% (95% confidence interval 6.8% to 12.8%) of patients had involved (tumour on ink) margins and 17.8% (13.0% to 23.9%) had tumour on ink or a close margin. The rate of distant recurrence was 25.4% (14.5% to 40.6%) in patients with tumour on ink, 8.4% (4.4% to 15.5%) in patients with tumour on ink or close, and 7.4% (3.9% to 13.6%) in patients with negative margins. Compared with negative margins, tumour on ink margins were associated with increased distant recurrence (hazard ratio 2.10, 95% confidence interval 1.65 to 2.69, P<0.001) and local recurrence (1.98, 1.66 to 2.36, P<0.001). Close margins were associated with increased distant recurrence (1.38, 1.13 to 1.69, P<0.001) and local recurrence (2.09, 1.39 to 3.13, P<0.001) compared with negative margins, after adjusting for receipt of adjuvant chemotherapy and radiotherapy. In five studies published since 2010, tumour on ink margins were associated with increased distant recurrence (2.41, 1.81 to 3.21, P<0.001) as were tumour on ink and close margins (1.44, 1.22 to 1.71, P<0.001) compared with negative margins. Conclusions Involved or close pathological margins after breast conserving surgery for early stage, invasive breast cancer are associated with increased distant recurrence and local recurrence. Surgeons should aim to achieve a minimum clear margin of at least 1 mm. On the basis of current evidence, international guidelines should be revised. Systematic review registration CRD42021232115. Data are available on reasonable request from the corresponding author (Bundredn{at}manchester.ac.uk).

中文翻译：

---

乳腺癌保留手术后的边缘状态和生存结果：前瞻性注册的系统评价和荟萃分析

目的确定边缘受累是否与远处复发相关，并确定所需的边缘以尽量减少早期浸润性乳腺癌的局部复发和远处复发。设计 前瞻性注册的系统回顾和文献荟萃分析。数据来源 Medline (PubMed)、Embase 和 Proquest 在线数据库。未发表的数据来自研究作者。合格标准 合格的研究报告了接受保乳手术的患者（对于 I-III 期乳腺癌），允许评估与边缘状态相关的结果，并随访患者至少 60 个月。仅患有导管原位癌或接受新辅助化疗或乳房切除术治疗的患者被排除在外。在适用的情况下，边缘被归类为墨水上的肿瘤（涉及），接近的边缘（墨水上没有肿瘤但 <2 毫米）和负边缘（≥2 毫米）。结果 纳入了 1980 年 1 月 1 日至 2021 年 12 月 31 日的 68 项研究，包括 112 140 名乳腺癌患者。在所有研究中，9.4%（95% 置信区间 6.8% 至 12.8%）的患者涉及（墨水上的肿瘤）边缘，17.8%（13.0% 至 23.9%）的患者有墨水上或接近边缘的肿瘤。墨水上肿瘤患者的远处复发率为 25.4%（14.5% 至 40.6%），墨水上或接近肿瘤的患者为 8.4%（4.4% 至 15.5%），7.4%（3.9% 至 13.6%）在切缘阴性的患者中。与阴性切缘相比，墨水切缘上的肿瘤与远处复发（风险比 2.10，95% 置信区间 1.65 至 2.69，P<0.001）和局部复发（1.98，1.66 至 2.36，P<0.001）增加相关。在调整接受辅助化疗和放疗后，与负切缘相比，接近切缘与增加的远处复发（1.38、1.13 至 1.69，P<0.001）和局部复发（2.09、1.39 至 3.13，P<0.001）相关。在自 2010 年以来发表的五项研究中，与阴性相比，墨水边缘的肿瘤与远处复发增加相关（2.41、1.81 至 3.21，P<0.001），墨水和接近边缘的肿瘤（1.44、1.22 至 1.71，P<0.001）与阴性复发相关。边距。结论 早期浸润性乳腺癌保乳术后病变累及或接近切缘与远处复发和局部复发增加有关。外科医生的目标应该是达到至少 1 毫米的最小净边缘。在现有证据的基础上，应修订国际指南。系统评价注册CRD42021232115。数据可根据通讯作者的合理要求提供 (Bundredn{at}manchester.ac.uk)。