Abstract
BACKGROUND: Perineural invasion (PNI) is recognized as a prognostic factor in several cancers, but its role in predicting axillary lymph node metastasis (ALNM) in early-stage breast cancer remains unclear. Understanding this association could provide insights for nodal staging in the era of axillary surgery de-escalation, guiding adjuvant treatment decisions. OBJECTIVES: To investigate and validate the association between PNI and both the presence and extent of ALNM in patients with early-stage operable invasive breast cancer. DESIGN: A retrospective cohort study and meta-analysis. METHODS: We conducted a retrospective study of patients with early-stage operable breast cancer who underwent surgery between June 2011 and June 2023 stratified by PNI status. Three matching methods-propensity score matching, inverse probability of treatment weighting, and overlap weighting-were used to minimize confounding. Multivariable logistic regression analysis was used to assess the association between PNI and both ALNM and lymph node ratio (LNR). In addition, a meta-analysis was conducted to verify these associations. RESULTS: Among 4156 patients, 1223 (29.4%) were PNI-positive. PNI-positive patients had a significantly higher incidence of ALNM (54.0% vs 32.1%) and increased lymph node burden (LNR >0.20). These associations remained significant after adjusting for confounding variables and through sensitivity analyses using the three matching methods (all p < 0.05). In the meta-analysis, 16 cohort studies comprising 17,451 participants met the selection criteria. The analysis confirmed a significant association between PNI and increased ALNM risk (odds ratio (OR), 3.30; 95% confidence interval (CI), 2.24-4.86), poorer disease-free survival (hazard ratio (HR), 1.84; 95% CI, 1.39-2.44), and poorer overall survival (HR, 1.64; 95% CI, 1.15-2.35). CONCLUSION: PNI is significantly associated with increased ALNM and lymph node burden in early-stage operable breast cancer. These findings support the clinical utility of PNI for risk stratification and as a potential indicator for guiding adjuvant treatment decisions.