Neoadjuvant Versus Adjuvant Chemo-Immunotherapy in Early-Stage Triple-Negative Breast Cancer: A National Cancer Database Study

Background/Objectives: While neoadjuvant chemo-immunotherapy has become a standard treatment for patients with early-stage triple-negative breast cancer (TNBC) based on KEYNOTE-522, the trial did not directly compare neoadjuvant with adjuvant chemo-immunotherapy. We compared treatment patterns and survival outcomes between neoadjuvant and adjuvant chemo-immunotherapy in real-world settings. Methods: We identified women with clinical stage II–III TNBC diagnosed from 2017–2023 in the National Cancer Database (NCDB) who underwent definitive surgery and received chemo-immunotherapy. Factors associated with neoadjuvant treatment were evaluated. Overall survival (OS) was assessed using Kaplan–Meier curves, univariable and multivariable Cox regression, and propensity-score overlap weighting. Prespecified subgroup analyses were performed by clinical T and N stage. Results: Among 21,757 women, 21,340 received neoadjuvant and 417 received adjuvant chemo-immunotherapy. Higher clinical T stage, node-positive disease, and diagnosis in 2021–2023 were associated with neoadjuvant treatment. One-, 2-, and 3-year OS were 98.8%, 93.2%, and 88.6% with neoadjuvant versus 94.3%, 88.9%, and 81.6% with adjuvant chemo-immunotherapy, respectively. Neoadjuvant treatment was associated with improved OS in univariable analysis (HR 0.58, 95% CI 0.46–0.72; p < 0.001), multivariable analysis (HR 0.52, 95% CI 0.42–0.66; p < 0.001), and after overlap weighting (HR 0.57, 95% CI 0.45–0.73; p < 0.001). Associations consistently favored neoadjuvant treatment across clinical T- and N-stage subgroups. Conclusions: In this retrospective NCDB study, neoadjuvant chemo-immunotherapy was associated with improved OS compared with adjuvant chemo-immunotherapy. These hypothesis-generating findings are consistent with current clinical practice but should be interpreted cautiously, as differences in treatment regimens and completion rates, which could not be assessed in the NCDB, may have contributed to the observed survival benefit.