Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis
AuthorsBundred, J. R.
Cutress, R. I.
Dahlstrom, J. E.
Bundred, Nigel J
AffiliationLeeds Institute of Molecular Medicine, University of Leeds, Leeds, UK
MetadataShow full item record
AbstractObjective: 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 Unpublished data were sought from study authors.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.
CitationBundred JR, Michael S, Stuart B, Cutress RI, Beckmann K, Holleczek B, et al. Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis. BMJ (Clinical research ed). 2022 Sep 21;378:e070346. PubMed PMID: 36130770. Pubmed Central PMCID: PMC9490551 at www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; NJB received a National Institute for Health and Care Research, Research for Patient Benefit grant investigating a margin device. The authors declare no other relationships or activities that could appear to have influenced the submitted work. Epub 2022/09/22. eng.
- Association of surgical margins with local recurrence in patients undergoing breast-conserving surgery after neoadjuvant chemotherapy.
- Authors: Lin J, Lin KJ, Wang YF, Huang LH, Chen SL, Chen DR
- Issue date: 2020 May 20
- Complete excision with narrow margins provides equivalent local control to wider excision in breast conservation for invasive cancer.
- Authors: Tang SSK, Rapisarda F, Nerurkar A, Osin P, MacNeill F, Smith I, Johnston S, Ross G, Mohammed K, Gui GPH
- Issue date: 2019 Apr
- Do surgical margins matter after mastectomy? A systematic review.
- Authors: Bundred J, Michael S, Bowers S, Barnes N, Jauhari Y, Plant D, Maishman T, Cutress R, Holleczek B, Dodwell D, Bundred N
- Issue date: 2020 Dec
- Close Margins Less Than 2 mm Are Not Associated With Higher Risks of 10-Year Local Recurrence and Breast Cancer Mortality Compared With Negative Margins in Women Treated With Breast-Conserving Therapy.
- Authors: Tyler S, Truong PT, Lesperance M, Nichol A, Baliski C, Warburton R, Tyldesley S
- Issue date: 2018 Jul 1
- Comparison of local recurrence after mastectomy for pure ductal carcinoma in situ with close or positive margins: A meta-analysis.
- Authors: Kim D, Ki Y, Kim W, Park D, Joo J, Jeon H, Nam J
- Issue date: 2020 Oct-Dec