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Peer-reviewedCC BY 4.0Frontiers in Oncology

Risk factors for non-sentinel lymph node metastasis in breast cancer: a meta-analysis

  • Lan Xu1,2
  • Kaiyue Wang2
  • Ziwei Chen2
  • Chunxia Deng1
  • Hong Zhang3,4,5
5 affiliations
  1. 1Department of General Surgery, Affiliated Renhe Hospital of China Three Gorges University
  2. 2Medical College, China Three Gorges University
  3. 3Nursing Department, Minda Hospital of Hubei Minzu University
  4. 4Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases, Minda Hospital of Hubei Minzu University
  5. 5Hubei Provincial Clinical Medical Research Center for Nephropathy, Minda Hospital of Hubei Minzu University
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Abstract

Objective: To systematically evaluate risk factors associated with non-sentinel lymph node (NSLN) metastasis in patients with sentinel lymph node (SLN)-positive breast cancer.

Methods: A comprehensive literature search was performed in PubMed, Embase, Web of Science, and the Cochrane Library from database inception to November 12, 2025. Studies reporting multivariable analyses of risk factors for NSLN metastasis were included. Study quality was independently assessed by two reviewers using the Newcastle–Ottawa Scale (NOS). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a random-effects model. Heterogeneity, sensitivity analyses, and publication bias were also evaluated. All statistical analyses were conducted using Stata version 15.0.

Results: A total of 37 studies involving 13,304 patients were included. The meta-analysis demonstrated that SLN macrometastasis (OR = 6.07, 95% CI: 2.21–16.7), abnormal preoperative AUS findings (OR = 3.51, 95% CI: 2.25–5.47), extranodal extension of SLN (OR = 2.67, 95% CI: 2.07 -3.44), lymphovascular invasion (OR = 2.68, 95% CI: 2.18–3.29), perineural invasion (OR = 2.37, 95% CI: 1.18–4.76), tumor diameter > 2 cm (OR = 2.06, 95% CI: 1.52–2.78), clinical T stage ≥ T2 (OR = 2.44, 95% CI: 2.02–2.95), histologic grade ≥ 3 (OR = 1.76, 95% CI: 1.44–2.16), number of positive SLNs (OR = 2.32, 95% CI: 1.53–3.53), SLN positivity ratio ≥ 50% (OR = 2.17, 95% CI: 1.74–2.70), multifocality (OR = 2.68, 95% CI: 1.98–3.63), HER2 positivity (OR = 2.22, 95% CI: 1.63–3.01), and a high Ki-67 index (OR = 2.20, 95% CI: 1.13–4.25) were associated with an increased risk of NSLN metastasis.

Conclusion: SLN tumor burden, abnormal preoperative axillary ultrasound findings, tumor aggressiveness, and intrinsic biological characteristics (e.g., HER2 status and Ki-67 index) are key predictors of NSLN metastasis. Given the limitations in the quality and quantity of the included studies, further high-quality, large-scale prospective studies are warranted to validate these findings and provide more robust evidence for individualized axillary management in breast cancer.

Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420261301905.

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Cite

BibTeXRIS
BibTeX
@article{xu2026risk,
  title = {{Risk factors for non-sentinel lymph node metastasis in breast cancer: a meta-analysis}},
  author = {Lan Xu and Kaiyue Wang and Ziwei Chen and Chunxia Deng and Hong Zhang},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1844072},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1844072/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Risk factors for non-sentinel lymph node metastasis in breast cancer: a meta-analysis
AU  - Lan Xu
AU  - Kaiyue Wang
AU  - Ziwei Chen
AU  - Chunxia Deng
AU  - Hong Zhang
PY  - 2026
DA  - 2026/10/29
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1844072
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1844072/full
AB  - Objective: To systematically evaluate risk factors associated with non-sentinel lymph node (NSLN) metastasis in patients with sentinel lymph node (SLN)-positive breast cancer.  Methods: A comprehensive literature search was performed in PubMed, Embase, Web of Science, and the Cochrane Library from database inception to November 12, 2025. Studies reporting multivariable analyses of risk factors for NSLN metastasis were included. Study quality was independently assessed by two reviewers using the Newcastle–Ottawa Scale (NOS). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a random-effects model. Heterogeneity, sensitivity analyses, and publication bias were also evaluated. All statistical analyses were conducted using Stata version 15.0.  Results: A total of 37 studies involving 13,304 patients were included. The meta-analysis demonstrated that SLN macrometastasis (OR = 6.07, 95% CI: 2.21–16.7), abnormal preoperative AUS findings (OR = 3.51, 95% CI: 2.25–5.47), extranodal extension of SLN (OR = 2.67, 95% CI: 2.07 -3.44), lymphovascular invasion (OR = 2.68, 95% CI: 2.18–3.29), perineural invasion (OR = 2.37, 95% CI: 1.18–4.76), tumor diameter > 2 cm (OR = 2.06, 95% CI: 1.52–2.78), clinical T stage ≥ T2 (OR = 2.44, 95% CI: 2.02–2.95), histologic grade ≥ 3 (OR = 1.76, 95% CI: 1.44–2.16), number of positive SLNs (OR = 2.32, 95% CI: 1.53–3.53), SLN positivity ratio ≥ 50% (OR = 2.17, 95% CI: 1.74–2.70), multifocality (OR = 2.68, 95% CI: 1.98–3.63), HER2 positivity (OR = 2.22, 95% CI: 1.63–3.01), and a high Ki-67 index (OR = 2.20, 95% CI: 1.13–4.25) were associated with an increased risk of NSLN metastasis.  Conclusion: SLN tumor burden, abnormal preoperative axillary ultrasound findings, tumor aggressiveness, and intrinsic biological characteristics (e.g., HER2 status and Ki-67 index) are key predictors of NSLN metastasis. Given the limitations in the quality and quantity of the included studies, further high-quality, large-scale prospective studies are warranted to validate these findings and provide more robust evidence for individualized axillary management in breast cancer.  Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420261301905.
SN  - 2234-943X
ER  -