Association of neoadjuvant chemotherapy dose intensity with pathological complete response and event-free survival in HER2-negative early breast cancer

Background In early-stage breast cancer (eBC), the efficacy of neoadjuvant chemotherapy (NACT) may be compromised by dose delays or reductions. A reduced relative dose intensity (RDI, i.e. the ratio of the delivered to planned chemotherapy dose), can lead to diminished clinical outcomes, but real-world data are limited in this setting. Methods We retrospectively analyzed data from HER2-negative eBC patients who received NACT at two Italian centers. RDI was assessed categorically with a 85 % threshold and continuously. We assessed the association between RDI and pathological complete response (pCR) and event-free survival (EFS) using regression analysis. Results 365 patients were included, comprising 218 triple-negative (TN) and 147 hormone receptor-positive (HR+) cases. In the TN cohort, 63.3 % of patients received a high RDI. High RDI was significantly associated with increased pCR rates in univariate and multivariate analyses (categorical RDI: OR 3.15, p < 0.001; continuous RDI: OR 1.05, p < 0.001). High RDI was associated with improved EFS in univariate analysis (categorical RDI: HR 0.48, p = 0.010; continuous RDI: HR 0.98, p = 0.011); however, this association was not retained in multivariate model adjusted for pCR, age, stage, and dose-dense chemotherapy. In the HR+ cohort, where 88.4 % of patients received a high RDI, no association was observed between RDI and pCR. Nevertheless, high RDI was significantly associated with improved EFS in univariate and multivariate models (categorical RDI: HR 0.29, p = 0.006; continuous RDI: HR 0.96, p = 0.004) adjusted for age, stage, and treatment schedule. Conclusion High RDI is associated with improved clinical outcomes in patients with HER2-negative eBC undergoing NACT. Maintaining an optimal RDI is crucial to maximize treatment efficacy in the curative setting.