Agreement: I AgreeBody: 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.
6Unit? 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
No competing Interests: YesThe following competing Interests: Electronic Publication Date: Sunday, November 13, 2022 – 13:47Highwire Comment Subject: Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysisWorkflow State: ReleasedFull Title: Re: Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis
Highwire Comment Response to: Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysisCheck this box if you would like your letter to appear anonymously:: Last Name: AristeiFirst name and middle initial: CynthiaEmail: cynthia.aristei@unipg.itAddress: Piazzale Giorgio Menghini 1, 06100 Perugia, Italy Occupation: Radiation OncologistOther Authors: Mario Taffurelli, Viviana Galimberti, Maria Cristina Leonardi, Luigi Cataliotti, Donatella Santini, on behalf of the Italian Senonetwork Working Group Affiliation: University of Perugia and Perugia General Hospital, ItalyBMJ: Additional Article Info: Rapid response