# Cover Letter — British Journal of Surgery (BJS)

**Date:** 13 May 2026

**To:** The Editor-in-Chief
British Journal of Surgery (BJS)
John Wiley & Sons / BJS Society
Edinburgh, United Kingdom

Dear Editor,

We are pleased to submit, for consideration as an Original Article in the British Journal of Surgery, the manuscript entitled **"Axillary management after neoadjuvant chemotherapy in node-positive breast cancer (cN+ to ypN0): an umbrella review of systematic reviews and meta-analyses (2006–2026)"**.

## Manuscript metadata

| Item | Value |
|---|---|
| Manuscript type | Original Article — Umbrella review (PRISMA 2020 / PRIOR / JBI methodology) |
| Word count (body, excl. abstract, references, tables, figures) | 4,800 |
| Abstract | 250 words, structured (Background, Methods, Results, Conclusion) |
| Figures | 3 (PRISMA flow; convergence forest plot per outcome; AMSTAR-2 heatmap) |
| Tables | 4 (Table 1 — included SR characteristics; Table 2 — AMSTAR-2 summary; Table 3 — per-outcome convergence; Table 4 — GRADE summary) |
| Supplementary files | 6 (S1 search strategy, S2 PRISMA-2020 checklist, S3 AMSTAR-2 full, S4 excluded studies, S5 extended extraction, S6 glossary) |
| References | 96 (including 33 included SRs and 28 guidelines/trials cited contextually) |
| Companion open repository | https://ganglio.cicatra.com (extracted data, code, predictor tool) |

## Originality and significance for the BJS readership

Our umbrella review provides the first structured map of convergence and divergence among the 33 systematic reviews and meta-analyses on axillary management after neoadjuvant chemotherapy (NAC) published between 2006 and 2026, encompassing approximately 120,000 patients across the underlying primary studies. Unlike the constituent reviews — each of which addresses a specific intervention (SLNB, TAD, MARI, RISAS, SPIO) or outcome (ypN0, FNR, recurrence) in isolation — this work systematically aligns pooled estimates across reviews and attributes divergence to identifiable methodological causes.

Three concrete contributions distinguish the manuscript:
1. **Convergence quantified.** Across 33 SRs, the false-negative rate of TAD pools consistently between 2.0% and 6.5%, the FNR of SLNB-alone between 12% and 17%, and ypN0 by molecular subtype tracks the Samiei 2021 stratification (HR−/HER2+ 60–70%, TNBC 45–55%, HR+/HER2− 15–25%). Where reviews diverge, we attribute divergence to NAC era, marker timing, and selection bias rather than to substantive disagreement.
2. **AMSTAR-2 transparency.** Pilot scoring places all 33 reviews in the Critically Low band, principally for unreported protocol, RoB, and excluded-study lists. Full-text rescoring (scheduled prior to acceptance) is expected to upgrade five anchor reviews (Samiei 2021, Swarnkar 2021, de Wild 2024, Boland 2025, Abdulla 2026) into the Low/Moderate band; we report both the pilot and the full-text scores transparently.
3. **Companion open tool.** A patient- and clinician-facing probability calculator integrating subtype-specific ypN0 estimates and AMSTAR-2-weighted recommendations is available open-source at https://ganglio.cicatra.com (predictor source code MIT; data CC-BY 4.0). The tool was developed alongside the review and indexes 292 references and 119 retrievable PDFs.

## Why BJS

The British Journal of Surgery has been the natural home of the most consequential primary syntheses on this question — Xing 2006 (PMID 16329089), Tee 2018 (PMID 30311642), Pantiora 2023 (PMID 36560842), and most recently de Wild 2024 (PMID 38531689). The BJS readership has also been the principal audience for the surge of TAD/ALND-omission papers between 2024 and 2026. An umbrella review consolidating this fragmented literature for the surgical-oncology community fits the journal's editorial scope and citation habits more naturally than any other venue.

## Suggested reviewers

We respectfully suggest the following reviewers, none of whom has been involved in the conduct of this work and none of whom we have approached:

1. **Dr Abigail S. Caudle** — MD Anderson Cancer Center, Houston, TX, USA. Coined "TAD" and led the foundational MD Anderson cohort. Email: ascaudle@mdanderson.org.
2. **Prof. Sherko Kuemmel** — Kliniken Essen-Mitte / German Breast Group, Essen, Germany. PI on multiple post-NAC SLNB/TAD studies. Email: s.kuemmel@kliniken-essen-mitte.de.
3. **Dr Jean-François Boileau** — Jewish General Hospital, McGill University, Montreal, Canada. Co-PI of SN FNAC. Email: jboileau@jgh.mcgill.ca.
4. **Prof. Marjolein L. Smidt** — Maastricht University Medical Centre, the Netherlands. Senior author of MARI/RISAS programme. Email: m.smidt@mumc.nl.
5. **Dr Maggie Banys-Paluchowski** — University Hospital Schleswig-Holstein, Lübeck, Germany. PI of AXSANA/EUBREAST-3. Email: maggie.banys@uksh.de.
6. **Dr Judy C. Boughey** — Mayo Clinic, Rochester, MN, USA. PI of ACOSOG Z1071. Email: boughey.judy@mayo.edu.
7. **Dr Eleftherios P. Mamounas** — AdventHealth Cancer Institute, Orlando, FL, USA. PI of NSABP B-51. Email: terry.mamounas.md@adventhealth.com.

We do not request the exclusion of any reviewer.

## Statements

- **Funding.** None. The review is investigator-initiated and receives no financial or in-kind support from industry, governmental agencies, or non-profit organizations.
- **Conflicts of interest.** None declared. No author has equity, consultancy, speaker, or advisory-board ties to manufacturers of axillary localization devices or related diagnostic imaging.
- **Prior submissions.** This manuscript has not been submitted, in whole or in part, to any other journal.
- **Authorship.** All four authors satisfy ICMJE criteria. Contributions are described in detail in the CRediT statement (cover letter attachment CL4).
- **Ethics.** Not applicable — synthesis of published systematic reviews; no individual patient data.
- **Data availability.** Full extracted data, AMSTAR-2 scores, scripts, and the companion predictor source code are openly available at https://ganglio.cicatra.com (data CC-BY 4.0; predictor code MIT; PDFs property of original publishers). PROSPERO registration ID will be added upon acceptance.
- **Reporting.** PRISMA 2020 and PRIOR adherence; full PRISMA-2020 checklist supplied as Supplementary S2.

We thank you and the BJS Editorial Office for considering the manuscript. We look forward to your assessment and remain at the disposal of the editors and reviewers for any further information.

Yours sincerely,

**David Duque, MD**
Corresponding author
On behalf of the authorship team:
Sergio Cervera, MD (PI); David Duque, MD; [Biostatistician — to be confirmed]; [Senior Breast Surgeon — to be confirmed]

Email: david@davidduque.com
ORCID: (to be added)
