# Structured Abstract

**Title:** Axillary Management After Neoadjuvant Chemotherapy in Node-Positive Breast Cancer: An Umbrella Review of 23 Systematic Reviews and Meta-Analyses (2006-2026)

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## Version A — 250 words (BJS / Br J Surg target)

**Background.** Between 30% and 45% of clinically node-positive (cN+) breast-cancer patients convert to ypN0 after neoadjuvant chemotherapy (NAC), creating opportunity to omit axillary lymph-node dissection (ALND). After strict PICOS triage of 33 originally screened systematic reviews, 23 (13 fully eligible plus 10 borderline retained for sensitivity analysis) on axillary technique, false-negative rate (FNR) and oncologic safety have been published since 2006, with overlapping primary studies and divergent recommendations.

**Methods.** Umbrella review per JBI methodology and PRIOR-O reporting. PubMed/MEDLINE, EMBASE, Cochrane CDSR and Epistemonikos were searched (Jan 2006 to Apr 2026; ~5,516 hits across four strands; 146 unique records after deduplication). Dual-independent screening, extraction and three-rater AMSTAR-2 scoring. Synthesis was narrative; no re-pooling of primary effect estimates. Convergence was cross-walked against seven contemporary clinical-practice guidelines and certainty graded with GRADE per outcome.

**Results.** Twenty-three SRs/MAs were retained after PICOS triage (13 ELIGIBLE for primary synthesis; 10 BORDERLINE for sensitivity analysis; ~95,000 cumulative patients across reviews; high overlap by corrected covered area). Three-rater AMSTAR-2 consensus across the 13 ELIGIBLE SRs: 3 Moderate, 4 Low, 6 Critically Low. Nodal pCR ranged from 56-72% (HR-/HER2+) and 38-50% (TNBC, conventional chemo) to 7-22% (HR+/HER2-), rising above 75% in TNBC with chemo-immunotherapy. FNR ranged from 16-20% (single-tracer SLNB) to 9-11% (dual-tracer SLNB ≥3 nodes), 7-8% (MARI), 1.4-4.2% (TAD) and 3.5% (RISAS). Five-year axillary recurrence after ALND omission was 1.0% in TAD-staged ypN0 patients (Montagna 2024).

**Conclusion.** TAD or RISAS, with dual tracer and ≥3 sentinel nodes, is the convergent technique standard. Selective ALND omission in TAD-confirmed ypN0 is endorsed by every contemporary guideline (NCCN, ESMO, ASCO, St Gallen, AGO, EUSOMA, EUBREAST). Persistent gaps include ITC handling, chemo-immunotherapy recalibration, patient-reported outcomes and Latin-American validation.

**Keywords.** breast cancer; neoadjuvant chemotherapy; targeted axillary dissection; sentinel lymph node; ypN0; umbrella review.

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## Version B — 300 words (EJSO / The Breast target)

**Background.** Between 30% and 45% of clinically node-positive (cN+) breast-cancer patients convert to ypN0 after neoadjuvant chemotherapy (NAC), and rates approach 70-75% in HER2-enriched disease and exceed 75% in triple-negative breast cancer (TNBC) treated with chemo-immunotherapy. Confirmatory axillary technique selection (sentinel-lymph-node biopsy [SLNB], MARI, targeted axillary dissection [TAD], RISAS or axillary lymph-node dissection [ALND]) is critical to enable selective ALND omission. From 33 originally screened systematic reviews and meta-analyses, 23 were retained after strict PICOS triage; primary-study overlap is extensive and recommendations diverge on false-negative-rate (FNR) thresholds, isolated-tumour-cell handling and regional radiotherapy.

**Methods.** Umbrella review per the JBI framework, reported per PRIOR-O and PRISMA 2020. PubMed/MEDLINE, EMBASE, Cochrane CDSR and Epistemonikos were searched (Jan 2006 to Apr 2026; four PubMed strands yielding ~5,516 hits; 146 unique records after deduplication). Dual-independent screening, data extraction and three-rater AMSTAR-2 scoring (LLM-augmented full-text plus two surgeon raters). Synthesis was narrative; no re-pooling. GRADE was applied per outcome. Findings were cross-walked against guidelines from NCCN, ESMO, ASCO, St Gallen, AGO, EUSOMA and EUBREAST.

**Results.** Twenty-three SRs/MAs were retained after PICOS triage (13 ELIGIBLE for primary synthesis; 10 BORDERLINE for sensitivity analysis; cumulative ~95,000 patients across reviews; corrected covered area indicated high overlap per Pieper 2014). Three-rater AMSTAR-2 consensus for the 13 ELIGIBLE SRs: 3 Moderate, 4 Low, 6 Critically Low. Nodal pCR ranges across reviews: 56-72% HR-/HER2+; 35-55% HR+/HER2+; 38-50% TNBC (conventional chemotherapy); 7-22% HR+/HER2-. FNR by technique: 16-20% single-tracer SLNB; 9-11% dual-tracer SLNB with ≥3 nodes; 7-8% MARI; 1.4-4.2% TAD; 3.5% RISAS. Multicenter long-term data (n=1,144) reported 5-year axillary recurrence of 1.0% (95% CI 0.49-2.0%) after ALND omission in TAD-staged ypN0 patients.

**Conclusion.** TAD (with dual tracer and ≥3 sentinel nodes) is the convergent standard for axillary staging when ALND omission is contemplated. Selective ALND omission in TAD-confirmed ypN0 is endorsed by every contemporary guideline. NSABP B-51 supports omission of regional nodal irradiation in cN1→ypN0. Priorities for future research include standardised reporting of isolated tumour cells, chemo-immunotherapy-era recalibration, lymphedema and patient-reported outcomes, and validation in under-represented Latin-American populations.

**Keywords.** breast cancer; neoadjuvant chemotherapy; targeted axillary dissection; sentinel lymph node biopsy; ypN0; umbrella review.

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*Version A is calibrated to the BJS 250-word abstract limit; Version B is calibrated to the EJSO / The Breast 300-word limit. Word counts will be recomputed after final edit; both versions revised 2026-05-14 to reflect the post-PICOS-triage 23-SR corpus (was 33). Sergio to verify final word counts before submission.*
