Exploring heterogeneity in survival benefit of neoadjuvant therapy for triple-negative breast cancer using causal...

The individual survival benefit of neoadjuvant therapy (NAT) for patients with triple-negative breast cancer (TNBC) remains uncertain. This study aimed to evaluate the individualized treatment effect (ITE) of NAT on event-free survival (EFS) in patients with TNBC using causal survival forests.

This study included 803 patients with TNBC from a retrospective clinical cohort at a tertiary hospital in Henan Province, China. The outcome was 3-year EFS. ITEs were estimated on the restricted mean survival time (RMST) scale. A positive ITE indicated predicted benefit from NAT. Model performance was evaluated using C-for-benefit, rank weighted average treatment effects, and calibration. Patients were grouped into ITE quartiles, and survival outcomes were compared according to predicted benefit group and treatment concordance.

Among 803 patients, 250 received NAT. The average treatment effect was -1.62 months. The predicted ITEs ranged from -7.92 months favoring No NAT to 3.67 months favoring NAT, indicating substantial heterogeneity in treatment benefit. The model showed positive ranking performance with an AUTOC of 5.67 months and the C-for-benefit was 0.537. Tumor size, clinical axillary lymph node status, and clinical N stage were the main contributors to predicted ITEs. In the Q1 and Q4 groups, concordant treatment was associated with an average RMST gain of 5.23 months.

Among patients with TNBC, CSF identified subgroups with different predicted directions and magnitudes of 3-year EFS benefit. Stratification based on ITEs may support individualized assessment of treatment benefit and provide a basis for future validation.