# Slide Deck — Journal Club / Tumor Board

**Format**: 12 slides · 30-minute presentation · Markdown source for Beamer/Reveal.js/PowerPoint export
**Last update**: 2026-05-14

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## Slide 1 — Cover

**Title**: Axillary Management After Neoadjuvant Chemotherapy in Node-Positive Breast Cancer

**Subtitle**: An Umbrella Review of 23 Systematic Reviews and Meta-Analyses (2006–2026)

- **Authors**: Cervera S, Duque D, et al.
- **Target journal**: British Journal of Surgery (primary) · EJSO (secondary)
- **Date**: May 2026
- **Companion tools**: ganglio.cicatra.com · open data repository
- **Conflicts of interest**: None declared
- **Funding**: Institutional only

> **Speaker notes** (~50 words): Introduce the umbrella review as a synthesis-of-syntheses tackling one of the highest-volume clinical questions in breast surgery. Note that 30 minutes will not cover everything; the open repository contains all extracted data. Invite questions throughout — this is a tumor board, not a viva.

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## Slide 2 — Why this question matters

**The cN+ → ypN0 paradigm shift**

- ~30–60% of cN+ patients now convert to ypN0 with modern systemic therapy
- Axillary lymph node dissection (ALND) carries 15–30% lifetime lymphoedema risk
- Sentinel lymph node biopsy (SLNB) alone after NAC has historically had unacceptable false-negative rates (FNR > 10%)
- Targeted axillary dissection (TAD) and dual mapping promised < 5% FNR — but evidence is heterogeneous
- Three pivotal trials (Z1071, SENTINA, SN FNAC) opened the door; ten more refined the technique
- 2024 NSABP B-51 reframed the role of axillary radiotherapy in ypN0/ypN+

> **Speaker notes**: Frame the burden — globally millions of women undergo NAC for breast cancer each year; ~half become node-negative. Avoiding ALND in this group is one of the highest-yield de-escalation opportunities in surgical oncology. Emphasise that the umbrella review answers the meta-question: *across the dozens of SRs published since Z1071, what do we actually know?*

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## Slide 3 — Pivotal trials timeline

**A 13-year arc of de-escalation**

- 2013 — **ACOSOG Z1071** (Boughey): SLNB after NAC in cN1 → FNR 12.6% (>10% threshold)
- 2013 — **SENTINA** (Kuehn): four-arm German trial, FNR 14.2% in cN1 → SLNB after NAC
- 2015 — **SN FNAC** (Boileau): immunohistochemistry-positive count → FNR 8.4%
- 2016 — **MARI** (Donker): clip retrieval alone → FNR 7%
- 2016 — **TAD concept** (Caudle, MD Anderson): SLNB + clipped node → FNR 1.4–2%
- 2021 — **RISAS** (Simons): radioactive iodine seed for clipped node → FNR 3.5%
- 2024 — **NSABP B-51** (Mamounas): no benefit of regional nodal RT in ypN0 (HR 0.92, 95% CI 0.69–1.22)

> **Speaker notes**: This timeline anchors every guideline. The umbrella review captures the SRs that aggregated these trials; we are not re-litigating individual trials but examining *how the syntheses have aggregated and interpreted them over a decade*. NSABP B-51 is so recent that only 2/23 SRs incorporate it — a key sensitivity-analysis point.

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## Slide 4 — Methods overview

**Umbrella review per JBI methodology**

- **Protocol**: PROSPERO-registered (placeholder ID); JBI Manual chapter 10 (Aromataris 2020); PRIOR reporting checklist (Gates 2022)
- **Search**: MEDLINE / Embase / Cochrane / Web of Science · 2006-01-01 to 2026-04-30 · no language limit
- **Inclusion**: SRs/MAs of cN+ → axillary surgery after NAC; report ypN0 rate, FNR, recurrence, or survival
- **PICOS triage**: post-hoc 3-tier classification (ELIGIBLE / BORDERLINE / EXCLUDED) — pre-specified rules; documented in Supplementary Table S2
- **Quality**: AMSTAR-2 (Shea 2017) by 3 raters: LLM (Claude Opus 4.7) + 2 surgeon-coauthors; Cohen κ pairwise + Fleiss κ overall
- **Certainty**: GRADE for 8 primary outcomes (Guyatt 2008)
- **No re-pooling**: by design — narrative + tabular synthesis (rationale in Slide 9)

> **Speaker notes**: Two methodological choices are likely to attract reviewer scrutiny. First, JBI vs PRIOR-O: we use JBI conduct but PRIOR reporting because PRIOR-O is a tool under development. Second, post-hoc PICOS triage: pragmatic response to the heterogeneity of the SR corpus; pre-specified before extraction; reported transparently.

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## Slide 5 — PRISMA flow

**From 1,847 records to 23 included SRs**

- **Identification**: 1,847 records (MEDLINE 612 · Embase 781 · Cochrane 198 · WoS 256)
- **Deduplication**: 1,124 unique records
- **Title/abstract screen**: 187 advanced
- **Full-text retrieval**: 156 obtained · 31 unobtainable (closed access — listed in `pendientes_acceso_cerrado/`)
- **Full-text screen**: 33 SRs initially eligible
- **PICOS triage outcome**:
  - 13 ELIGIBLE (primary synthesis)
  - 10 BORDERLINE (sensitivity synthesis — partial PICOS overlap)
  - 10 EXCLUDED (PICOS rationale documented per record)
- **Final corpus**: 23 SRs for AMSTAR-2 + GRADE; 13 SRs drive primary conclusions

> **Speaker notes**: The 23/10 split is the headline number reviewers will probe. Show the PRISMA 2020 diagram with the third tier (BORDERLINE) — this is non-standard and we note it explicitly. The 10 EXCLUDED SRs each have a documented PICOS exclusion reason in Supplementary Table S3.

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## Slide 6 — ypN0 rates by intrinsic subtype

**The single most actionable finding**

| Subtype                  | ypN0 rate (range across SRs) | Pooled estimate (illustrative) |
|--------------------------|------------------------------|--------------------------------|
| HER2-enriched (HER2+)    | 56–72%                       | ~65%                           |
| Triple-negative (TNBC)   | 38–50% (chemotherapy alone)  | ~45%                           |
| HR+/HER2-                | 7–22%                        | ~15%                           |

- Subtype is the dominant predictor — overwhelms baseline nodal burden in most SRs
- HER2-targeted dual blockade (trastuzumab + pertuzumab) drives the upper bound for HER2+
- TNBC + immunotherapy (pembrolizumab per KEYNOTE-522) shifts the upper bound but is captured in only 3/23 SRs
- HR+/HER2- shows minimal nodal response — caution before de-escalating

> **Speaker notes**: This is the slide every clinician remembers. Stress the chemo-IO gap for TNBC — most SRs in the corpus pre-date pembrolizumab. The HR+/HER2- patient remains the population least served by axillary de-escalation.

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## Slide 7 — False-negative rate by surgical technique

**Targeted approaches consistently beat single-tracer SLNB**

- **TAD** (clipped node + dual-tracer SLNB): pooled FNR < 5% (range 1.4–6.2% across SRs)
- **SLNB with dual mapping (radiocolloid + blue dye)** + ≥3 nodes retrieved: FNR 8–10%
- **SLNB single tracer** or < 3 nodes: FNR 16–20%
- **Clipped-node-alone (MARI-style)**: FNR 5–7%
- **Magnetic seed / RFID alternatives** (RISAS, MagSeed): non-inferior to wire/iodine seed
- **TAD requires**: pre-NAC clipping, post-NAC localisation (wire/seed/RFID/magnetic), retrieval confirmation (specimen radiograph)

> **Speaker notes**: TAD is the clear winner methodologically, but operational complexity matters: clipping rates remain < 60% in most real-world cohorts. The conversation in tumor board often shifts here from *what should we do?* to *can we actually do it consistently?*

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## Slide 8 — Long-term oncological outcomes

**Recurrence and survival data**

- **Montagna 2022 pooled cohort** (n = 1,144 ypN0 after NAC, SLNB-only, no ALND): 5-year axillary recurrence **1.0%** (95% CI 0.5–1.7%)
- **Galimberti 2022** (IBCSG 23-01 long-term follow-up, surrogate context): no OS detriment with axillary preservation in low-burden disease
- **Wong 2021** SR (n = 5,879): 3-year axillary recurrence after SLNB-only post-NAC = 0.4–1.5%
- **NSABP B-51 (2024)**: regional nodal RT did not improve invasive breast-cancer recurrence-free interval in ypN0/ypN+ post-NAC (HR 0.92)
- **Caveat**: median follow-up 3–5 years across most SRs — late axillary recurrences (5–10 yr) under-represented
- **GRADE**: Moderate certainty for axillary recurrence; Low for OS/DFS due to short follow-up + indirectness

> **Speaker notes**: The 1% recurrence number is the strongest single argument for de-escalation. NSABP B-51 lifts the radiotherapy concern that had limited surgical de-escalation. Emphasise the follow-up caveat — late recurrences in HR+ disease may yet emerge.

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## Slide 9 — AMSTAR-2 + GRADE summary

**3-rater quality assessment**

- **AMSTAR-2 distribution (13 ELIGIBLE)**: 0 High · 3 Moderate · 4 Low · 6 Critically Low
- **AMSTAR-2 distribution (23 total incl. BORDERLINE)**: 0 High · 4 Moderate · 8 Low · 11 Critically Low
- **Inter-rater agreement** (Cohen κ pairwise): 0.21–0.38 (slight to fair); Fleiss κ = 0.27
- Disagreement clustered on items 2 (protocol) and 9 (RoB judgements) — abstract-only RoB reporting
- **GRADE summary across 8 outcomes**:
  - ypN0 rate by subtype — Moderate
  - FNR (TAD) — Moderate
  - FNR (SLNB single) — Moderate
  - Axillary recurrence — Moderate
  - DFS — Low (indirectness, short FU)
  - OS — Low (imprecision)
  - Lymphoedema — Low (selective reporting)
  - QoL — Very Low (sparse data)

> **Speaker notes**: The slight-to-fair κ is uncomfortable but typical for AMSTAR-2 (published κ values 0.20–0.50). We mitigate with consensus adjudication and full per-rater export. Reviewers will ask about LLM use — we frame Claude Opus as a third independent rater, with full audit trail.

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## Slide 10 — Guideline convergence

**Major societies aligned**

- **NCCN 2026 v2** (US): TAD or SLNB with ≥3 nodes acceptable for cN1 → ycN0 → consider omitting ALND if all SLN/clipped nodes negative
- **ESMO 2024** (Europe): same de-escalation pathway endorsed; cautions in cN2/cN3
- **ASCO 2025 update**: TAD preferred where feasible; SLNB single-tracer no longer recommended
- **St Gallen 2025** consensus: ≥75% panel votes endorsing TAD as standard for cN1→ycN0
- **AGO Mamma 2026** (Germany): ++/++ recommendation for TAD; ALND only if residual disease confirmed
- **SESPM (Spain) 2025**: aligned with ESMO; specific note on Latin American resource-limited adaptations

> **Speaker notes**: The convergence across guidelines is striking — but the umbrella review shows that the underlying SR evidence base is more heterogeneous than the guideline narrative suggests. This is a useful counterweight in tumor-board discussions where dogma can outpace data.

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## Slide 11 — Practice-changing implications

**Six points to take to Monday's clinic**

- **(1)** Clip every biopsy-proven node before NAC — operationally non-negotiable
- **(2)** Default to TAD (clipped node + dual-tracer SLNB) for cN1 → ycN0 candidates
- **(3)** Subtype-stratified counselling: HER2+ and TNBC patients have a high probability of ypN0 conversion; HR+/HER2- much lower
- **(4)** Specimen radiograph confirming clip retrieval is mandatory — not optional
- **(5)** Avoid SLNB with single tracer or < 3 nodes — it fails the FNR threshold
- **(6)** NSABP B-51 supports omitting regional nodal RT in ypN0; multidisciplinary discussion still required

> **Speaker notes**: Frame these as the *operational delta* between current practice and the synthesised evidence. Most centres will already be doing 3–4 of these; the umbrella review provides the citation backing for the remaining 2–3.

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## Slide 12 — Open questions + companion tools

**Where do we go next**

- **Open questions**:
  - Chemo-IO era impact on ypN0 — only 3/23 SRs include KEYNOTE-522
  - Lobular / inflammatory / metaplastic subtypes — under-represented
  - cN2/cN3 patients — most evidence excludes them
  - Late recurrence (5–10 yr) in HR+ ypN0 — follow-up immature
  - Patient-reported outcomes — sparse, heterogeneous
- **Companion tools**:
  - Web predictor: **ganglio.cicatra.com** (subtype-stratified ypN0 calculator)
  - Open data repository: AMSTAR-2 per-rater scores, GRADE evidence tables, PICOS triage rationale, full extraction sheets
- **Call to action**: contribute prospectively to a federated registry — see project README
- **Acknowledgements**: 2 surgeon-coauthor raters; LLM tooling (Claude Opus 4.7 1M); SESPM working group

> **Speaker notes**: End on the open-science angle — the repository is the durable contribution. Invite the audience to identify SRs we may have missed before submission. Mention that the web predictor is a separate manuscript-in-preparation but is freely available now for clinical use, with appropriate disclaimers.
