Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis
BMJ 2022; 378 doi: https://doi.org/10.1136/bmj-2022-070346 (Published 21 September 2022) Cite this as: BMJ 2022;378:e070346Linked Research
Width of excision margins after breast conserving surgery for invasive breast cancer and distant recurrence and survival
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Dear Editor,
Tumor free margin: wider is better
This review article has gathered all the evidence about the impact of margin status on local and distant metastasis and survival among patients who had undergone breast cancer conservation surgery (BCS). Yet, there is no international consensus regarding the width of margin to be excised around the early-stage breast cancers that are subjected to BCS. The authors have quoted studies from UK, USA, and other European nations having different recommendations for margins. At the same time, the article itself has given varied statement showing difference of 1 mm between the heading 'Conclusion: 'A margin of no tumour on ink is inadequate and we recommend a minimum tumour free distance of 1 mm from the margin...' and the heading 'What this study adds: '....close margins (no tumour on ink, but tumour <2 mm) were associated with increased distant recurrence compared with wider margins'.(1)
The evidence available so far mandates the International Association or Society of Oncology to standardize the method of measurement of width from the tumor margin on the table, considering the fact that this is a live tissue which is going to 'shrink' by the time it reaches the pathologist, and the measurement would definitely vary. In addition, on table frozen section biopsy from the margin is a helpful tool to ensure adequate tumor free margin rather than subjecting the patient for re-excision, which causes pain, distress, complications, increased cost and take away avoidable extra O.T time. It is bit difficult to comprehend if a margin of 2mm or a bit more would dramatically affect cosmesis, which will psychologically prove more disastrous than leaving a tumor positive or with a close margin.
Though the paper is silent about grade of tumor, which is an independent risk factor for recurrence, it could be included in future study. Same thing goes for margin on the under-surface of the tumor, how far it is from the chest muscles, if it is too close like the margin on the periphery, it will have the same impact.
References:
Bundred James R, Michael S, Stuart B Beth. Margin status and survival outcomes after breast cancer conservation surgery: Prospectively registered systematic review and meta-analysis. BMJ 2022;378:e070346
Competing interests: No competing interests
Re: Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis
Dear Editor,
We read with interest the metanalysis and the “Fast Facts” by Bundred et al. (1,2) which assessed whether margin involvement after breast conserving surgery (BCS) for early breast cancer was associated with distant recurrence. This analysis of 68 studies comprising 112.140 patients led to the conclusion that pathologically involved or close margins were associated with more distant and local recurrences. Consequently, surgeons were invited to achieve a minimum clear margin of at least 1 mm. Another clear message was that, on the basis of current evidence, international guidelines (3) should be revised.
We are writing in response to this statement. In 2016 the Working Group of the Italian Senonetwork (4), focused its attention on surgical resection margins after BCS and provided its recommendations (5) which were upgraded in 2020 (6). In accordance with the Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) consensus guideline (3), margins were defined as positive or negative but it was decided that more information was required.
Additional specifications for a positive margin (ink on the lesion) included identifying a) which margin(s); b) invasive foci, whether single or multiple; c) the linear extent of margin involvement in millimeters; d) an in situ ductal component. For a tumor-free (negative) margin (no ink on the lesion) the distance should be specified between the lesion and the macroscopically sampled margins (5,6).
Moreover, as, in our view, a well-defined cut-off for margin status is not the only indicator of the risk of relapse, as clinical and bio-pathological features all impact upon risk stratification, we provided indications to appropriate post-operative radiation therapy (RT) schedule which, besides taking margin status into account, needs to factor in disease features by means of multidisciplinary decision-making (5,6).
Because of the high risk of recurrence re-excision is the standard approach to multiple positive margins. It is, however, beset by several potential obstacles: patients may refuse it, re-excision may be associated with positive margins, it may not be technically possible and the patient may refuse a mastectomy. In all these instances, we recommended an RT boost with a maximum dose of 20 Gy (or equivalent dose in hypo-fractionated schedules). Higher doses should be avoided because of the increased risk of adverse side effects and poor cosmetic outcome. Patients need to be aware that in these cases RT is second-line treatment and is not associated with the same success rate as surgery.
When only 1 margin is positive, approaches include either re-excision or RT with a boost doses, generally no higher than 20 Gy (or equivalent in hypo-fractionated schedules). The decision will be based on the linear margin extent and the presence of other risk factors for local recurrence (e.g., young age, large tumor size, high grade, lymph node involvement, extensive intraductal component, high Ki-67).
For a negative margin whether to administer boost or not depends on the presence of risk factors for relapse. The RT dose may vary; higher doses are administered in selected high-risk cases with short surgical margins from the tumor.
Adding other patient- and tumour- related factors to the binary of negative/positive margins and their width, contributes to a precision tailored approach to early breast cancer patients who have undergone BCS.
Cynthia Aristei1, Mario Taffurelli2, Viviana Galimberti3, Maria Cristina Leonardi4, Luigi Cataliotti5, Donatella Santini6, on behalf of the Italian Senonetwork Working Group
1Radiation Oncology Section, University of Perugia and Perugia General Hospital, Italy
2Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna and IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Italy
3Division of Breast Cancer Surgery, IEO, European Institute of Oncology, IRCCS, Milan, Italy
4Division of Radiation Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy
5A.P.S. Senonetwork Italia, Florence, Italy.
6Unità Operativa di Anatomia e Istologia Patologica, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
References
1. Bundred JR, Michael S, Stuart B, et al. Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis. BMJ 2022; 378:e070346 http://dx.doi.org/10.1136/ bmj-2022-070346
2. Bundred NJ, Bundred JR, Cutress RI, et al. Width of excision margins after breast conserving surgery for invasive breast cancer and distant recurrence and survival BMJ 2022; 378:o2077 http://dx.doi.org/10.1136/bmj.o2077
3. Moran MS, Schnitt SJ, Giuliano AE, et al. Society of Surgical Oncology - American Society for Radiation Oncology Consensus Guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. Int J Radiat Oncol Biol Phys 2014; 88:553-564, http://dx.doi.org/10.1016/j.ijrobp.2013.11.012
4. https://www.senonetwork.it
5. Galimberti V, Taffurelli M, Leonardi MC, et al. Surgical resection margins after breast-conserving surgery: Senonetwork recommendations. Tumori 2016; 102: 284-289 DOI: 10.5301/tj.5000500
6. Focus on: Margini di resezione chirurgica dopo chirurgia conservativa 2020. https://www.senonetwork.it/C_Common/Download.asp?file=/$Site$/files/doc/Documenti/raccomandazioni/Focus_on_MARGINI_DI_RESEZIONE_CHIRURGICA_DOPO_CHIRURGIA_CONSERVATIVA_2020.pdf
Competing interests: No competing interests