# Cover Letter — The Breast (EUSOMA / EUSOBI / European Society of Breast Cancer Specialists)

**Date:** 13 May 2026

**To:** The Editor-in-Chief
The Breast — Official Journal of the European Society of Breast Cancer Specialists (EUSOMA), the European Society of Breast Imaging (EUSOBI), and the Senologic International Society (SIS)
Elsevier Ltd, London / Oxford, UK

Dear Editor,

We are pleased to submit, for consideration as an Original Article in The Breast, 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 (included SR characteristics; AMSTAR-2 summary; per-outcome convergence; 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 (33 included SRs + 28 guidelines/trials cited contextually) |
| Companion open repository | https://ganglio.cicatra.com |

## Originality and significance

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. The synthesis is structured by intervention (SLNB, TAD, MARI, RISAS, MLNB, SPIO) and by outcome (ypN0, false-negative rate, identification rate, locoregional recurrence, overall and disease-free survival, lymphedema), with a transparent ±2 percentage-point convergence rule and explicit attribution of divergence to methodological causes (NAC era, marker timing, selection bias).

Three principal findings address questions of immediate relevance to The Breast's multidisciplinary readership of breast surgeons, breast radiologists, breast pathologists, and breast medical oncologists:
1. The false-negative rate of TAD converges between 2.0% and 6.5% across nine meta-analyses — below the conventional 10% ceiling — supporting de-escalation in well-selected patients regardless of marker technology.
2. Axillary pCR (ypN0) by molecular subtype follows a steep gradient (HR−/HER2+ 60–70%, TNBC 45–55%, HR+/HER2− 15–25%), with a marked post-2018 era effect attributable to dual HER2 blockade and chemo-immunotherapy.
3. The five anchor reviews (Samiei 2021, Swarnkar 2021, de Wild 2024, Boland 2025, Abdulla 2026) provide convergent estimates across geographies and tracer modalities, supporting the operational use of TAD as the standard de-escalated approach in cN+ → ycN0 patients in 2026.

Companion deliverable: an open-source patient- and clinician-facing probability calculator at https://ganglio.cicatra.com integrates subtype-specific ypN0 estimates and AMSTAR-2-weighted recommendations.

## Why The Breast

The Breast is the natural multidisciplinary venue for an umbrella review on axillary management because: (i) it is the official journal of EUSOMA, whose 2023 axillary-surgery position paper (Rubio et al, PMID 38199146) is one of the principal hand-searched documents in our review; (ii) The Breast has consistently published the convergence/divergence work that an umbrella synthesis depends on, including the Cao 2021 meta-analysis (PMID 34325383); (iii) the journal's truly multidisciplinary readership matches the cross-specialty implications of de-escalation (surgeon, radiologist, pathologist, medical oncologist); and (iv) the journal's commitment to open access aligns with our companion open-source predictor and CC-BY 4.0 data deposit.

## Suggested reviewers

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

1. **Prof. Isabel T. Rubio** — Clinica Universidad de Navarra, Madrid, Spain. Lead author of EUSOMA 2023 axillary position paper. Email: irubio@unav.es.
2. **Prof. Maria João Cardoso** — Champalimaud Foundation, Lisbon, Portugal. Past president of EUSOMA. Email: mariajoao.cardoso@fundacaochampalimaud.pt.
3. **Prof. Oreste Davide Gentilini** — IRCCS San Raffaele, Milan, Italy. SOUND PI; EUSOMA leadership. Email: gentilini.oreste@hsr.it.
4. **Prof. Lorenza Marotti** — EUSOMA, Florence, Italy. Quality-criteria methodologist. Email: marotti@eusoma.org.
5. **Prof. Sibylle Loibl** — German Breast Group, Neu-Isenburg, Germany. Lead author ESMO 2023 guideline (PMID 38101773). Email: sibylle.loibl@gbg.de.
6. **Dr Massimo Cristofanilli** — Weill Cornell Medicine, New York, NY, USA. Multidisciplinary breast oncology. Email: mac9795@med.cornell.edu.
7. **Dr Maggie Banys-Paluchowski** — University Hospital Schleswig-Holstein, Lübeck, Germany. PI of AXSANA/EUBREAST-3. Email: maggie.banys@uksh.de.

We do not request the exclusion of any reviewer.

## Statements

- **Funding.** None.
- **Conflicts of interest.** None declared.
- **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 detailed in the CRediT statement.
- **Ethics.** Not applicable — synthesis of published systematic reviews; no individual patient data.
- **Data availability.** Full extracted data, AMSTAR-2 scores, scripts, and companion predictor source code openly available at https://ganglio.cicatra.com (data CC-BY 4.0; predictor code MIT). PROSPERO registration ID will be added upon acceptance.
- **Reporting.** PRISMA 2020 and PRIOR adherence; PRISMA-2020 checklist supplied as Supplementary S2.
- **Open access.** We confirm our willingness to publish under The Breast's open-access (gold) route; APC will be paid by the corresponding author from non-industry funds.

We thank you and the Editorial Office for considering the manuscript.

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)
