Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis
Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis
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 Unpublished data were sought from study authors.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.
Breast Neoplasms, Breast/pathology, Female, Humans, Margins of Excision, Mastectomy, Mastectomy, Segmental, Neoplasm Recurrence, Local
Bundred, James R.
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Michael, Sarah
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Stuart, Beth
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Cutress, Ramsey I.
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Beckmann, Kerri
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Holleczek, Bernd
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Dahlstrom, Jane E.
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Gath, Jacqui
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Dodwell, David
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Bundred, Nigel J.
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21 September 2022
Bundred, James R.
93bff3ab-6ce4-4449-a6c1-d38d7f17f61f
Michael, Sarah
8899c89a-30bf-4164-821c-519ff7c41cd8
Stuart, Beth
a51c80d3-5855-4672-b24f-8c65fd2e1444
Cutress, Ramsey I.
68ae4f86-e8cf-411f-a335-cdba51797406
Beckmann, Kerri
f2242eea-070d-4d1e-ac7c-4e8d7d52b3e3
Holleczek, Bernd
f98e319e-3ac9-415e-b208-1b8ddc41fa08
Dahlstrom, Jane E.
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Gath, Jacqui
3c0b3b75-4f16-49ee-8fd5-b788a5a45ecb
Dodwell, David
a554c94f-ac82-4394-b826-b17c96e809d3
Bundred, Nigel J.
4ceba3cc-eae4-45ed-ba6f-7c07c7bfcb75
Bundred, James R., Michael, Sarah, Stuart, Beth, Cutress, Ramsey I., Beckmann, Kerri, Holleczek, Bernd, Dahlstrom, Jane E., Gath, Jacqui, Dodwell, David and Bundred, Nigel J.
(2022)
Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis.
BMJ (Clinical research ed.), 378, [e070346].
(doi:10.1136/bmj-2022-070346).
Abstract
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.
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bmj-2022-070346.full
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Accepted/In Press date: 28 July 2022
Published date: 21 September 2022
Additional Information:
Funding Information:
Funding: No funding was received for this work. However, DD received funding from Cancer Research UK (C8225/A21133).
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© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Keywords:
Breast Neoplasms, Breast/pathology, Female, Humans, Margins of Excision, Mastectomy, Mastectomy, Segmental, Neoplasm Recurrence, Local
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Local EPrints ID: 473370
URI: http://eprints.soton.ac.uk/id/eprint/473370
ISSN: 0959-8138
PURE UUID: 5cc9a55c-6d03-4116-89f2-cf20e72ead54
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Date deposited: 17 Jan 2023 17:35
Last modified: 16 Mar 2024 23:35
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Contributors
Author:
James R. Bundred
Author:
Sarah Michael
Author:
Beth Stuart
Author:
Kerri Beckmann
Author:
Bernd Holleczek
Author:
Jane E. Dahlstrom
Author:
Jacqui Gath
Author:
David Dodwell
Author:
Nigel J. Bundred
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