Perineural invasion and risk of lymph node metastasis in early-stage operable breast cancer: a large-scale propensity-matched cohort study and meta-analysis

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.