# Supplementary Material S6 — Glossary of Abbreviations and Definitions

**Manuscript:** Axillary management after neoadjuvant chemotherapy in node-positive breast cancer (cN+ to ypN0): an umbrella review of systematic reviews and meta-analyses (2006–2026).

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## 1. Clinical / surgical terms

| Term | Expansion / Definition |
|---|---|
| **ALND** | Axillary Lymph Node Dissection — surgical removal of levels I and II (and selectively III) axillary lymph nodes; historically the standard of care for cN+ breast cancer. |
| **SLNB** | Sentinel Lymph Node Biopsy — selective removal of the first draining lymph node(s), identified intraoperatively by a tracer (radioisotope, blue dye, ICG, SPIO, or combinations). |
| **TAD** | Targeted Axillary Dissection — combined SLNB plus selective excision of the previously biopsied and marked node, regardless of marker type or timing (one-step vs two-step procedure). Coined by Caudle et al, 2016 (PMID 26527775). |
| **MLNB** | Marked Lymph Node Biopsy — excision of the previously biopsied and marked node alone, without sentinel mapping. |
| **MARI** | Marking the Axillary lymph node with Radioactive Iodine seeds — Dutch single-centre protocol for selective excision of the marked node using ¹²⁵I seed localization (Donker et al, 2015 PMID 25775066). |
| **RISAS** | Radioactive Iodine Seed localization in the Axilla after neoadjuvant chemotherapy and Surgery — Dutch multi-centre prospective protocol combining MARI with SLNB for staging post-NAC (Simons et al, 2022 PMID 35107569). |
| **NAC** | Neoadjuvant Chemotherapy — systemic chemotherapy administered before definitive surgery, with the intent of downstaging the tumour and the axilla. Synonyms used in the literature: NACT, NST (neoadjuvant systemic therapy), PST (primary systemic therapy). |
| **NACT** | Neoadjuvant Chemotherapy (alternative abbreviation, common in UK and Asian-Pacific literature). |
| **NST** | Neoadjuvant Systemic Therapy — broader umbrella including chemotherapy, HER2-directed therapy, immunotherapy, and endocrine therapy when administered preoperatively. |
| **PST** | Primary Systemic Therapy — synonym of NST, common in European literature. |
| **NET** | Neoadjuvant Endocrine Therapy — preoperative endocrine treatment, usually for postmenopausal HR+/HER2− patients; tabulated separately from NAC. |
| **pCR** | Pathologic Complete Response — absence of residual invasive cancer at the time of definitive surgery (typically defined as ypT0/is ypN0 per FDA 2014 guidance). |
| **ypN0** | Pathologic complete response in the axillary lymph nodes after NAC (no residual nodal disease on final pathology). |
| **ypT0** | Pathologic complete response in the breast after NAC (no residual invasive disease in the breast). |
| **ypT0/is ypN0** | Combined pCR — no residual invasive disease in breast (ductal carcinoma in situ allowed) and no residual nodal disease. |
| **cN+** | Clinically node-positive — biopsy- or cytology-confirmed nodal metastasis at diagnosis (cN1, cN2, or cN3). |
| **cN0** | Clinically node-negative — no clinical or imaging evidence of nodal metastasis at diagnosis. |
| **ycN0** | Clinically node-negative status reassessed after NAC by clinical exam and imaging (typically ultrasound), in the absence of pathological confirmation. |
| **LRR** | Locoregional Recurrence — recurrence in the breast/chest wall, axilla, supraclavicular, or internal-mammary nodes. |
| **OS** | Overall Survival — time from diagnosis (or randomization) to death from any cause. |
| **DFS** | Disease-Free Survival — time from diagnosis (or randomization) to first recurrence (loco-regional or distant) or death from any cause. |
| **DDFS** | Distant Disease-Free Survival — time to distant recurrence or death; excludes loco-regional events. |
| **iDFS** | Invasive Disease-Free Survival — modern composite endpoint per STEEP 2.0 criteria. |
| **HR (in oncology)** | Hormone Receptor — refers to estrogen and progesterone receptor status (HR+ if ER and/or PR positive). |
| **HR (in survival analysis)** | Hazard Ratio — ratio of event hazards in two arms; <1 favours the index arm. |
| **HER2** | Human Epidermal Growth Factor Receptor 2 — overexpression/amplification status (positive if IHC 3+ or ISH-amplified). |
| **TNBC** | Triple-Negative Breast Cancer — ER-negative, PR-negative, HER2-negative. |
| **DCIS** | Ductal Carcinoma In Situ — non-invasive breast cancer; not eligible for the present synthesis when isolated. |
| **LCIS** | Lobular Carcinoma In Situ — risk lesion; not eligible. |
| **ITC** | Isolated Tumour Cell(s) — small clusters of tumour cells ≤0.2 mm or fewer than 200 cells in a lymph node section; classified as pN0(i+). |
| **IHC** | Immunohistochemistry — staining technique used to detect ER, PR, HER2, and cytokeratins (the latter for ITC detection). |
| **ICG** | Indocyanine Green — fluorescent dye used as a sentinel-node tracer. |
| **SPIO** | Superparamagnetic Iron Oxide — magnetic-particle tracer (commercial: Sienna+ / Magtrace) used for sentinel-node detection. |
| **RNI** | Regional Nodal Irradiation — adjuvant radiotherapy to axillary, supraclavicular, and/or internal-mammary nodes. |
| **PMRT** | Post-Mastectomy Radiotherapy — adjuvant radiotherapy after mastectomy. |

## 2. Diagnostic accuracy and statistical terms

| Term | Expansion / Definition |
|---|---|
| **FNR** | False-Negative Rate — proportion of patients with disease (per the reference standard) misclassified as negative by the index test. In axillary surgery: FNR = (false negatives) / (false negatives + true positives) of the index test (SLNB/TAD/MARI/RISAS), with completion ALND as the reference standard. The 10% threshold (Krag 2010) is the conventional acceptability ceiling. |
| **IR** | Identification Rate — proportion of attempted procedures in which the index test successfully identifies/retrieves the target node (sentinel node and/or marked node). |
| **NPV** | Negative Predictive Value — proportion of negative index-test results that are true negatives. |
| **PPV** | Positive Predictive Value — proportion of positive index-test results that are true positives. |
| **OR** | Odds Ratio — ratio of odds of event in two groups; >1 favours the comparator. |
| **RR** | Risk Ratio (Relative Risk) — ratio of probabilities in two groups. |
| **HR** | Hazard Ratio (see above). |
| **CI** | Confidence Interval — typically 95% CI; the interval that would contain the true parameter on 95% of repeated samples. |
| **I²** | Higgins I² statistic — proportion of total variability in a meta-analysis attributable to between-study heterogeneity rather than chance. Conventional bands: low (<25%), moderate (25–50%), substantial (50–75%), considerable (>75%). |
| **τ²** | Tau-squared — between-study variance in a random-effects meta-analysis. |
| **χ²** | Chi-square test for heterogeneity (Cochran's Q). |
| **CCA** | Corrected Covered Area — measure of overlap of primary studies across systematic reviews in an umbrella review (Pieper et al, *J Clin Epidemiol* 2014). Bands: slight (0–5%), moderate (6–10%), high (11–15%), very high (>15%). |
| **NMA** | Network Meta-Analysis — meta-analysis combining direct and indirect evidence across multiple comparators. |

## 3. Methodological / quality terms

| Term | Expansion / Definition |
|---|---|
| **PRISMA** | Preferred Reporting Items for Systematic Reviews and Meta-Analyses — reporting standard (Page MJ et al, *BMJ* 2021;372:n71. doi:10.1136/bmj.n71). |
| **PRIOR** | Preferred Reporting Items for Overviews of Reviews — reporting standard for overviews of reviews (Pollock M et al, *BMJ* 2023;381:e074091. doi:10.1136/bmj-2022-074091). |
| **JBI** | Joanna Briggs Institute — methodology body whose Manual for Evidence Synthesis (Aromataris 2024 update) provides the umbrella-review method used here. |
| **PICOS** | Population, Intervention, Comparator, Outcome, Study design — eligibility frame. |
| **PROSPERO** | International Prospective Register of Systematic Reviews — UK NIHR-hosted registry (https://www.crd.york.ac.uk/prospero/). |
| **AMSTAR-2** | A MeaSurement Tool to Assess systematic Reviews — 16-item appraisal tool (Shea BJ et al, *BMJ* 2017;358:j4008. doi:10.1136/bmj.j4008). Overall confidence rated High / Moderate / Low / Critically Low. |
| **ROBIS** | Risk Of Bias In Systematic reviews — 21-item tool focused on risk of bias rather than reporting (Whiting P et al, *J Clin Epidemiol* 2016). |
| **GRADE** | Grading of Recommendations Assessment, Development and Evaluation — system for rating certainty of evidence and strength of recommendations. Certainty bands: High / Moderate / Low / Very Low. |
| **RoB** | Risk of Bias (generic; may refer to RoB 2.0 for RCTs or ROBINS-I for non-randomized studies). |
| **CRediT** | Contributor Roles Taxonomy — structured authorship contribution statement (Brand A et al, *Learn Publ* 2015;28:151–155). |
| **ICMJE** | International Committee of Medical Journal Editors — authorship and reporting conventions. |
| **CONSORT** | Consolidated Standards of Reporting Trials — RCT reporting standard. |
| **STARD** | Standards for Reporting of Diagnostic Accuracy Studies. |
| **STROBE** | Strengthening the Reporting of Observational Studies in Epidemiology. |

## 4. Trial / study acronyms cited

| Term | Expansion / Definition |
|---|---|
| **ACOSOG Z0011** | American College of Surgeons Oncology Group trial demonstrating non-inferiority of SLNB-only vs ALND in selected cN0 patients with 1–2 positive sentinels (Giuliano 2017 PMID 28898379). |
| **ACOSOG Z1071** | Multicentre prospective trial assessing FNR of SLNB after NAC in cN1–cN2 patients (Boughey 2013 PMID 24061922). |
| **SENTINA** | German prospective trial assessing SLNB before vs after NAC across four cohorts (Kuehn 2013 PMID 23788107). |
| **SN FNAC** | Canadian prospective trial assessing SLNB after NAC with strict immunohistochemistry (Boileau 2015 PMID 25646192). |
| **GANEA-2** | French prospective multicentre cohort on SLNB after NAC (Classe 2019 PMID 30630666). |
| **MARI** | Dutch single-centre validation of marked-node retrieval after NAC (Donker 2015 PMID 25775066). |
| **RISAS** | Dutch multicentre prospective trial combining marked-node retrieval and SLNB (Simons 2022 PMID 35107569). |
| **AXSANA / EUBREAST-3** | International prospective registry tracking real-world axillary surgery in cN+ → NAC patients (Banys-Paluchowski 2023 PMID 36868251). |
| **ATNEC** | UK MRC RCT comparing axillary treatment (ALND vs RNI) vs no further treatment in ypN0 patients after NAC (Goyal 2024). |
| **NSABP B-51 / RTOG 1304** | Phase III RCT of regional nodal irradiation in ypN0 patients converting from cN+ after NAC (Mamounas 2024 PMID 38598574). |
| **Alliance A011202** | Phase III RCT of ALND vs axillary radiation in ypN+ residual disease after NAC. |
| **INSEMA** | German RCT of SLNB omission in selected cN0 patients (Reimer 2024 PMID 39555828). |
| **SOUND** | Italian RCT of SLNB omission in cN0 patients with cT1 disease and negative axillary US. |
| **TAXIS** | OPBC-03 / SAKK 23/16 RCT comparing TAD/SLNB + RNI vs ALND + RNI in cN+ patients. |
| **KEYNOTE-522** | RCT of pembrolizumab plus chemotherapy in early TNBC; introduced the chemo-immunotherapy era (Schmid 2020 NEJM). |

## 5. Outcome thresholds and benchmarks

| Term | Expansion / Definition |
|---|---|
| **10% FNR threshold** | Conventional acceptability ceiling for sentinel-node staging in clinically node-positive disease after NAC; established by Krag et al (NSABP B-32) and applied across SENTINA, SN FNAC, Z1071, and subsequent SR/MAs. |
| **Three-node rule** | Pragmatic criterion derived from Z1071 / SN FNAC: SLNB reliable (FNR <10%) when ≥3 sentinel nodes are retrieved with dual tracer. |
| **±2 percentage-point convergence** | Pragmatic convergence rule used in this umbrella review: pooled estimates from independent SRs are deemed convergent if their point estimates differ by ≤2 absolute percentage points or their 95% CIs overlap. |

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*Glossary compiled by the review team; cross-referenced with NCCN, ESMO, AGO, EUSOMA, and EUBREAST glossaries.*
