Association of neoadjuvant therapy with locoregional recurrence according to recurrence definitions in breast cancer: a retrospective cohort study

The impact of neoadjuvant therapy (NAT) on locoregional recurrence (LRR) remains controversial, particularly due to differences in recurrence definitions and the presence of competing events such as distant metastasis. This study aimed to evaluate the association between NAT and LRR using distinct recurrence definitions and appropriate analytical approaches. We conducted a retrospective cohort study of patients with invasive breast cancer who underwent surgery at a single institution. LRR was evaluated using two definitions: Any LRR, defined as locoregional recurrence regardless of distant metastasis, and True LRR, defined as isolated locoregional recurrence without distant metastasis. Multivariable Cox regression, propensity score–based inverse probability of treatment weighting (IPTW), and competing risk analysis using the Fine–Gray model were applied. A total of 1,670 patients were included, of whom 323 received NAT and 1,347 did not. During a median follow-up of approximately 52.8 months, 79 patients (4.7%) developed Any LRR and 51 patients (3.1%) developed True LRR. NAT was observed to be associated with a higher incidence of Any LRR in multivariable analysis. Although a similar trend was observed for True LRR, the association did not consistently reach statistical significance across models. Competing risk analysis yielded similar findings for True LRR when distant metastasis was treated as a competing event. NAT was observed to be associated with a higher incidence of LRR in this retrospective cohort study; however, this association should be interpreted with caution due to substantial residual confounding and temporal heterogeneity. No causal relationship between NAT and LRR can be established. Instead, these findings highlight the importance of recurrence definitions and analytical approaches, including competing risk methods, in interpreting locoregional outcomes. These results should be considered hypothesis-generating and warrant further validation in well-designed studies.